<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01709578</url>
  </required_header>
  <id_info>
    <org_study_id>EFC10832</org_study_id>
    <secondary_id>U1111-1115-8466</secondary_id>
    <secondary_id>2011-003538-16</secondary_id>
    <nct_id>NCT01709578</nct_id>
  </id_info>
  <brief_title>To Evaluate The Effect Of SAR153191 (REGN88) Added To Other RA Drugs In Patients With RA Who Are Not Responding To Or Intolerant Of Anti-TNF Therapy (SARIL-RA-TARGET)</brief_title>
  <official_title>A Randomized, Double-blind, Parallel, Placebo-controlled Study Assessing the Efficacy and Safety of Sarilumab Added to Non-biologic DMARD Therapy in Patients With Rheumatoid Arthritis Who Are Inadequate Responders to or Intolerant of TNF-α Antagonists</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Regeneron Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Sanofi</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary Objective:&#xD;
&#xD;
      To demonstrate that sarilumab added to disease modifying anti-rheumatic drugs (DMARDs) were&#xD;
      effective for:&#xD;
&#xD;
        -  reduction of signs and symptoms at Week 24 and&#xD;
&#xD;
        -  improvement of physical function at Week 12&#xD;
&#xD;
      in participants with active rheumatoid arthritis (RA) who were inadequate responders or&#xD;
      intolerant to tumor necrosis factor alpha (TNF-α) antagonists.&#xD;
&#xD;
      Secondary Objectives:&#xD;
&#xD;
      The secondary objectives were to investigate the effects of SAR153191 (REGN88) when added to&#xD;
      DMARD therapy, in participants with active RA who were inadequate responders or intolerant to&#xD;
      TNF-α antagonists, for:&#xD;
&#xD;
        -  Reduction of signs and symptoms at Week 12;&#xD;
&#xD;
        -  Improvement in physical function at Week 24;&#xD;
&#xD;
        -  Improvement in disease activity score as measured by other American College of&#xD;
           Rheumatology (ACR) derived components at Weeks 12 and 24;&#xD;
&#xD;
        -  Improvement in quality of life as measured by participant reported outcomes (PROs) at&#xD;
           intermediate visits and Week 24.&#xD;
&#xD;
      To assess the exposure of sarilumab added to DMARD therapy in this population.&#xD;
&#xD;
      To assess the safety of sarilumab in this population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Total study duration was up to 34 weeks: screening up to 28 days, treatment phase of 24&#xD;
      weeks, and post-treatment follow-up of 6 weeks.&#xD;
&#xD;
      After completion of the treatment phase of this study, participant were eligible to enter a&#xD;
      long term safety study (LTS11210) for active treatment with SAR153191 (REGN88).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">March 2015</completion_date>
  <primary_completion_date type="Actual">March 2015</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants Who Achieved at Least 20% Improvement in the American College of Rheumatology (ACR20) Criteria at Week 24</measure>
    <time_frame>Week 24</time_frame>
    <description>ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: tender joint count (TJC); swollen joint count (SJC); levels of an acute phase reactant (C-reactive Protein levels [CRP]); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by (health assessment questionnaire disability index [HAQ-DI]). ACR20 is defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments of the ACR.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>Physical function was assessed by HAQ-DI. It consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. Least-squares (LS) means and standard errors (SE) at Week 12 were obtained from a mixed-effect model with repeated measures (MMRM) with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline HAQ-DI as a covariate.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Disease Activity Score for 28 Joints -C-Reactive Protein (DAS28--CRP) Score at Week 24</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); General health (GH) assessment by the participant assessed from the ACR rheumatoid arthritis (RA) core set questionnaire (participant global assessment) in 100 mm visual analog scale (VAS). Marker of inflammation assessed by the high sensitivity C-reactive protein (hs-CRP) in mg/L. The DAS28 score provides a number indicating the current disease activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline DAS28-CRP score as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving ACR50 Criteria at Week 24</measure>
    <time_frame>Week 24</time_frame>
    <description>ACR responses are assessed with a composite rating scale that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR50 is defined as achieving at least 50% improvement in both TJC and SJC, and at least 50% improvement in at least 3 of the 5 other assessments of the ACR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving ACR70 Criteria at Week 24</measure>
    <time_frame>Week 24</time_frame>
    <description>ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR70 is defined as achieving at least 70% improvement in both TJC and SJC, and at least 70% improvement in at least 3 of the 5 other assessments of the ACR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP) &lt;2.6 at Week 24</measure>
    <time_frame>Week 24</time_frame>
    <description>DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR rheumatoid arthritis core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>CDAI is a composite index constructed to measure clinical remission in RA that does not include a laboratory test, and is a numerical summation of 4 components: TJC (28 joints), SJC (28 joints), Participant's Global Assessment of Disease Activity VAS (in cm), and Physician's Global Assessment of Disease VAS (in cm). Total scores ranges from 0 to 76 with a negative change in CDAI score indicating an improvement in disease activity and a positive change in score indicating a worsening of disease activity. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline CDAI as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in HAQ-DI at Week 24</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>Physical function was assessed by HAQ-DI. It consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline HAQ-DI as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Physical Component Summary Scores (PCS) at Week 24</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>SF-36 is a generic 36-item questionnaire measuring health-related quality of life (HRQL) covering 2 summary measures: PCS and mental component summary (MCS). The SF-36 consists of 8 subscales. The PCS had 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS had 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 24 by MMRM with treatment,region,number of previous anti TNFs,visit,and treatment-by-visit interaction as fixed effects and baseline SF-36 (PCS) as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in SF-36 MCS at Week 24</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>SF-36 is a generic 36-item questionnaire measuring HRQL covering 2 summary measures: PCS and MCS. The SF-36 consists of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline SF-36 MCS as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-fatigue) Score at Week 24</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>The FACIT-Fatigue is a 13-item questionnaire assessing fatigue where participants scored each item on a 5-point scale (0-4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. A total score ranging from 0 to 52. A higher score corresponded to a lower level of fatigue. A positive change from baseline score indicates an improvement. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline FACIT-fatigue as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Morning Stiffness VAS at Week 24</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>RA is associated with stiffness of joints, especially in the morning after prolonged stationery state. The degree of stiffness can be an indicator of disease severity. The severity of morning stiffness was assessed on a VAS scale from 0 mm (no problem) to 100 mm (major problem). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline Morning Stiffness as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Week 24: Work Days Missed Due to RA</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days missed in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in WPS-RA at Week 24: Days With Work Productivity Reduced by ≥ 50% Due to RA</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days with reduced productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in WPS-RA at Week 24: RA Interference With Work Productivity</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Interference in the last month with work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to RA</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with no household work in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in WPS-RA at Week 24: Days With Household Work Productivity Reduced by ≥ 50% Due to RA</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with reduced household work productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in WPS-RA at Week 24: Days With Family/Social/Leisure Activities Missed Due to RA</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days missed of family/social/leisure activities in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to RA</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with outside help hired in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in WPS-RA at Week 24: RA Interference With Household Work Productivity</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). The RA interference in the last month with household work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Scores at Week 24</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>RAID is a composite measure of the impact of RA on participants that takes into account 7 domains: pain, functional disability, fatigue, physical and emotional well being, quality of sleep, and coping. The RAID is calculated based on 7 numerical rating scales (NRS) questions. Range of the final RAID value is 0-10 where 0= not affected, very good and 10 = most affected weighted and calculated with a total score range of 0 (not affected, very good) to 10 (most affected). A higher RAID value indicate worse status and lower indicate not affected. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline RAID as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in European Quality of Life-5 Dimension 3 Level (EQ-5D-3L) VAS Scores at Week 24</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>The EQ-5D-3L is a standardized, generic measure of health outcome. It was designed for self-completion by participants. It was specifically included to address concerns regarding the health economic impact of RA. The EQ-5D-3L comprises 5 questions on mobility, self-care, pain, usual activities, and psychological status with 3 possible answers for each item (1=no problem, 2=moderate problems, 3=severe problems) and a vertical VAS that allows the participants to indicate their health state today that can range from 0 (worst imaginable) to 100 (best imaginable). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline EQ-5D-3L Scores as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving ACR20, ACR50 and ACR70 Criteria at Week 12</measure>
    <time_frame>Week 12</time_frame>
    <description>ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR20 is defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments of the ACR. ACR50 is defined as achieving at least 50% improvement in both TJC and SJC, and at least 50% improvement in at least 3 of the 5 other assessments of the ACR. ACR70 is defined as achieving at least 70% improvement in both TJC and SJC, and at least 70% improvement in at least 3 of the 5 other assessments of the ACR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in DAS28-CRP at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR rheumatoid arthritis core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline DAS score as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving Clinical Remission Score (DAS28--CRP &lt;2.6) at Week 12</measure>
    <time_frame>Week 12</time_frame>
    <description>DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR RA core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in SF-36 at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>SF-36 is a generic 36-item questionnaire measuring HRQL covering 2 summary measures: PCS and MCS. The SF-36 consists of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline SF-36 as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in WPS-RA at Week 12: Work Days Missed Due to RA</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days missed in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in WPS-RA at Week 12: Days With Work Productivity Reduced by ≥ 50% Due to RA</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days with reduced productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in WPS-RA at Week 12: RA Interference With Work Productivity</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Interference in the last month with work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in WPS-RA at Week 12: House Work Days Missed Due to RA</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with no household work in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in WPS-RA at Week 12: Days With Household Work Productivity Reduced by ≥ 50% Due to RA</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with reduced household work productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in WPS-RA at Week 12: Days With Family/Social/Leisure Activities Missed Due to RA</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days missed of family/social/leisure activities in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in WPS-RA at Week 12: Days With Outside Help Hired Due to RA</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with outside help hired in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in WPS-RA at Week 12: RA Interference With Household Work Productivity</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). The RA interference in the last month with household work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the FACIT-fatigue at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>The FACIT-Fatigue is a 13-item questionnaire assessing fatigue where participants scored each item on a 5-point scale (0-4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. A total score ranging from 0 to 52. A higher score corresponded to a lower level of fatigue. A positive change from baseline score indicates an improvement. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline FACIT-fatigue as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in EQ-5D-3L VAS Scores at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>The EQ-5D-3L is a standardized, generic measure of health outcome. EQ-5D was designed for self-completion by participants. The EQ-5D was specifically included to address concerns regarding the health economic impact of RA. The EQ-5D-3L comprises 5 questions on mobility, self-care, pain, usual activities, and psychological status with 3 possible answers for each item (1=no problem, 2=moderate problems, 3=severe problems) and a vertical VAS that allows the participants to indicate their health state today that can range from 0 (worst imaginable) to 100 (best imaginable). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline EQ-5D-3L scores as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in RAID Scores at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>RAID score is a composite measure of the impact of RA on participants that takes into account 7 domains: pain, functional disability, fatigue, physical and emotional well being, quality of sleep, and coping. The RAID is calculated based on 7 NRS questions. Range of the final RAID value is 0-10 where 0= not affected, very good and 10 = most affected weighted and calculated with a total score range of 0 (not affected, very good) to 10 (most affected). A higher RAID value indicates worse status and lower indicates not affected. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline RAID scores as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Individual ACR Components - TJC and SJC at Week 12 and Week 24</measure>
    <time_frame>Baseline, Week 12 and Week 24</time_frame>
    <description>ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS,HAQ-DI &amp; CRP. 68 joints were assessed for tenderness (TJC scoring 0-68) and 66 joints for swelling (SJC scoring 0-66). The 66 SJC evaluated the following joints: temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, interphalangeal of thumb, distal interphalangeal, proximal interphalangeal, knee, ankle mortise, ankle tarsus, metatarsophalangeal, interphalangeal of great toe, and proximal/distal interphalangeal of the toes. The TJC examined hip joints, in addition to the joints assessed for SJC. Increase in number of tender joints/swollen joints indicated severity. LS mean and SE at Week 12 &amp; 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 12 and Week 24</measure>
    <time_frame>Baseline, Week 12 and Week 24</time_frame>
    <description>ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI &amp; CRP. Physician global VAS &amp; participant global VAS was done by 100 mm non-anchored VAS, from no arthritis (0) activity to maximal arthritis (100) activity. Pain VAS by 100 mm VAS ranging from 0 &quot;no pain&quot; to 100 &quot;worst pain&quot;. LS mean and SE at Week 12 &amp; 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Individual ACR Component - CRP Level at Week 12 and Week 24</measure>
    <time_frame>Baseline, Week 12 and Week 24</time_frame>
    <description>ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI &amp; CRP. An elevated CRP level was considered a non-specific &quot;marker&quot; for RA. A reduction level indicates improvement. LS mean and SE at Week 12 &amp; 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Individual ACR Component - HAQ-DI at Week 12 and Week 24</measure>
    <time_frame>Baseline, Week 12 and Week 24</time_frame>
    <description>ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS,HAQ-DI &amp; CRP. HAQ-DI consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. LS mean and SE at Week 12 &amp; 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">546</enrollment>
  <condition>Rheumatoid Arthritis</condition>
  <arm_group>
    <arm_group_label>Placebo q2w</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo matched to sarilumab once every 2 weeks (q2w) was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sarilumab 150 mg q2w</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sarilumab 150 mg q2w was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sarilumab 200 mg q2w</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sarilumab 200 mg q2w was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sarilumab</intervention_name>
    <description>Pharmaceutical form:solution Route of administration: subcutaneous</description>
    <arm_group_label>Sarilumab 150 mg q2w</arm_group_label>
    <arm_group_label>Sarilumab 200 mg q2w</arm_group_label>
    <other_name>SAR153191</other_name>
    <other_name>REGN88</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>Pharmaceutical form:solution Route of administration: subcutaneous</description>
    <arm_group_label>Placebo q2w</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>hydroxychloroquine</intervention_name>
    <description>Dispensed according to the local practice.</description>
    <arm_group_label>Placebo q2w</arm_group_label>
    <arm_group_label>Sarilumab 150 mg q2w</arm_group_label>
    <arm_group_label>Sarilumab 200 mg q2w</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>methotrexate</intervention_name>
    <description>Dispensed according to the local practice.</description>
    <arm_group_label>Placebo q2w</arm_group_label>
    <arm_group_label>Sarilumab 150 mg q2w</arm_group_label>
    <arm_group_label>Sarilumab 200 mg q2w</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>sulfasalazine</intervention_name>
    <description>Dispensed according to the local practice.</description>
    <arm_group_label>Placebo q2w</arm_group_label>
    <arm_group_label>Sarilumab 150 mg q2w</arm_group_label>
    <arm_group_label>Sarilumab 200 mg q2w</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>leflunomide</intervention_name>
    <description>Dispensed according to the local practice.</description>
    <arm_group_label>Placebo q2w</arm_group_label>
    <arm_group_label>Sarilumab 150 mg q2w</arm_group_label>
    <arm_group_label>Sarilumab 200 mg q2w</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
        Diagnosis of RA ≥6 months duration, according to the ACR /European League against&#xD;
        Rheumatism (EULAR) 2010 RA Classification Criteria&#xD;
&#xD;
        ACR Class I-III functional status, based on 1991 revised criteria&#xD;
&#xD;
        Anti-TNF therapy failures, defined by the investigator as participants with an inadequate&#xD;
        clinical response, after being treated for at least 3 consecutive months, and/or&#xD;
        intolerance to at least 1 anti-TNF blocker(s), resulting in or requiring their&#xD;
        discontinuation:&#xD;
&#xD;
          -  TNF-blockers included, but were not limited to, etanercept, infliximab, adalimumab,&#xD;
             golimumab and/or certolizumab&#xD;
&#xD;
        Moderate-to-severely active RA&#xD;
&#xD;
        Continuous treatment with one or a combination of DMARDs (except for simultaneous&#xD;
        combination use of leflunomide and methotrexate) for at least 12 weeks prior to baseline&#xD;
        and on a stable dose(s) for at least 6 weeks prior to screening:&#xD;
&#xD;
          -  Methotrexate - 6 to 25 mg/week orally or parenterally&#xD;
&#xD;
          -  Leflunomide - 10 to 20 mg orally daily&#xD;
&#xD;
          -  Sulfasalazine - 1000 to 3000 mg orally daily&#xD;
&#xD;
          -  Hydroxychloroquine - 200 to 400 mg orally daily&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
        Participants &lt;18 years of age or legal adult age&#xD;
&#xD;
        Past history of, or current, autoimmune or inflammatory systemic or localized joint&#xD;
        disease(s) other than RA&#xD;
&#xD;
        History of juvenile idiopathic arthritis or arthritis onset prior to age 16&#xD;
&#xD;
        Severe active systemic RA, including but not limited to vasculitis, pulmonary fibrosis,&#xD;
        and/or Felty's syndrome.&#xD;
&#xD;
        Treatment with anti-TNF agents, as follows:&#xD;
&#xD;
          -  Within 28 days prior to the baseline visit - etanercept&#xD;
&#xD;
          -  Within 42 days prior to the baseline visit - infliximab, adalimumab, golimumab,&#xD;
             certolizumab pegol&#xD;
&#xD;
        Treatment with previous RA-directed biologic agents with other than TNF antagonist&#xD;
        mechanisms:&#xD;
&#xD;
        Within 28 days prior to the randomization (baseline) visit - anakinra Within 42 days prior&#xD;
        to the randomization (baseline) visit - abatacept&#xD;
&#xD;
        Within 6 months prior to the randomization (baseline) visit - any cell depleting agents&#xD;
        including but not limited to rituximab without a normal lymphocyte and cluster of&#xD;
        differentiation (CD) 19+ lymphocyte count&#xD;
&#xD;
        Treatment with any DMARD other than those allowed per protocol and limited to the maximum&#xD;
        specified dosage within 12 weeks prior to baseline&#xD;
&#xD;
        Treatment with prednisone &gt;10 mg or equivalent per day, or change in dosage within 4 weeks&#xD;
        prior to baseline visit&#xD;
&#xD;
        Any parenteral or intra-articular glucocorticoid injection within 4 weeks prior to baseline&#xD;
&#xD;
        Prior treatment with anti-interleukin (IL) -6 or IL-6 receptor antagonist therapies,&#xD;
        including tocilizumab or sarilumab, participation in a prior study of sarilumab,&#xD;
        irrespective of treatment arm&#xD;
&#xD;
        Prior treatment with a Janus kinase inhibitor (such as tofacitinib)&#xD;
&#xD;
        New treatment or dose-adjustment to ongoing medication for dyslipidemia within 6 weeks&#xD;
        prior to randomization, ie, stable dose for at least 6 weeks prior to randomization&#xD;
&#xD;
        Participation in any clinical research study evaluating another investigational drug or&#xD;
        therapy within 5 half-lives or 60 days of first investigational medicinal product (IMP)&#xD;
        administration, whichever was longer&#xD;
&#xD;
        History of alcohol or drug abuse within 5 years prior to the screening visit&#xD;
&#xD;
        Participants with a history of malignancy other than adequately-treated carcinoma in-situ&#xD;
        of the cervix, nonmetastatic squamous cell or basal cell carcinoma of the skin, within 5&#xD;
        years prior to the randomization (baseline) visit. Nonmalignant lymphoproliferative&#xD;
        disorders were also excluded&#xD;
&#xD;
        Participants with active tuberculosis or latent tuberculosis infection&#xD;
&#xD;
        The above information was not intended to contain all considerations relevant to a&#xD;
        participant's potential participation in a clinical trial&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Sciences &amp; Operations</last_name>
    <role>Study Director</role>
    <affiliation>Sanofi</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Investigational Site Number 840070</name>
      <address>
        <city>Anniston</city>
        <state>Alabama</state>
        <zip>36207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840138</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840142</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840134</name>
      <address>
        <city>Fullerton</city>
        <state>California</state>
        <zip>92835</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840141</name>
      <address>
        <city>Glendale</city>
        <state>California</state>
        <zip>85304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840111</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840135</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92120</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840021</name>
      <address>
        <city>Santa Maria</city>
        <state>California</state>
        <zip>94354</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840100</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840049</name>
      <address>
        <city>Upland</city>
        <state>California</state>
        <zip>91786</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840131</name>
      <address>
        <city>Whittier</city>
        <state>California</state>
        <zip>90606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840201</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840130</name>
      <address>
        <city>Lewes</city>
        <state>Delaware</state>
        <zip>19958</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840125</name>
      <address>
        <city>DeBary</city>
        <state>Florida</state>
        <zip>32713</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840048</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33155</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840024</name>
      <address>
        <city>Naples</city>
        <state>Florida</state>
        <zip>34102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840006</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840128</name>
      <address>
        <city>Ormond Beach</city>
        <state>Florida</state>
        <zip>32174</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840063</name>
      <address>
        <city>Palm Harbor</city>
        <state>Florida</state>
        <zip>34684</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840060</name>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840140</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33614</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840126</name>
      <address>
        <city>Vero Beach</city>
        <state>Florida</state>
        <zip>32960</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840018</name>
      <address>
        <city>Idaho Falls</city>
        <state>Idaho</state>
        <zip>83404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840110</name>
      <address>
        <city>Meridian</city>
        <state>Idaho</state>
        <zip>83642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840052</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160-7321</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840015</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40504</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840120</name>
      <address>
        <city>Baton Rouge</city>
        <state>Louisiana</state>
        <zip>70809</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840109</name>
      <address>
        <city>Lake Charles</city>
        <state>Louisiana</state>
        <zip>70601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840055</name>
      <address>
        <city>Frederick</city>
        <state>Maryland</state>
        <zip>21702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840150</name>
      <address>
        <city>Lansing</city>
        <state>Michigan</state>
        <zip>48910</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840137</name>
      <address>
        <city>Saint Clair Shores</city>
        <state>Michigan</state>
        <zip>48081</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840037</name>
      <address>
        <city>Tupelo</city>
        <state>Mississippi</state>
        <zip>38801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840112</name>
      <address>
        <city>Lincoln</city>
        <state>Nebraska</state>
        <zip>68516</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840106</name>
      <address>
        <city>Orchard Park</city>
        <state>New York</state>
        <zip>14127</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840121</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840115</name>
      <address>
        <city>Roslyn</city>
        <state>New York</state>
        <zip>11576</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840118</name>
      <address>
        <city>Smithtown</city>
        <state>New York</state>
        <zip>11787</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840139</name>
      <address>
        <city>Syracuse</city>
        <state>New York</state>
        <zip>13210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840123</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840116</name>
      <address>
        <city>Wilmington</city>
        <state>North Carolina</state>
        <zip>28401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840127</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840011</name>
      <address>
        <city>Tulsa</city>
        <state>Oklahoma</state>
        <zip>74104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840009</name>
      <address>
        <city>Duncansville</city>
        <state>Pennsylvania</state>
        <zip>16635</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840117</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840062</name>
      <address>
        <city>Reading</city>
        <state>Pennsylvania</state>
        <zip>19611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840058</name>
      <address>
        <city>Columbia</city>
        <state>South Carolina</state>
        <zip>29204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840025</name>
      <address>
        <city>Jackson</city>
        <state>Tennessee</state>
        <zip>38305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840059</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38119</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840132</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78731</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840022</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840114</name>
      <address>
        <city>El Paso</city>
        <state>Texas</state>
        <zip>79902</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840133</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77008</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840129</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77074</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840074</name>
      <address>
        <city>Mesquite</city>
        <state>Texas</state>
        <zip>75150</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840036</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 840124</name>
      <address>
        <city>Clarksburg</city>
        <state>West Virginia</state>
        <zip>26301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 032015</name>
      <address>
        <city>Buenos Aires</city>
        <zip>32015</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 032008</name>
      <address>
        <city>Buenos Aires</city>
        <zip>C1428DZF</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 032019</name>
      <address>
        <city>Caba</city>
        <zip>1180</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 032006</name>
      <address>
        <city>Caba</city>
        <zip>C1015ABO</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 032016</name>
      <address>
        <city>Capital Federal</city>
        <zip>1425</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 032020</name>
      <address>
        <city>Cordoba</city>
        <zip>X5119XAA</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 032017</name>
      <address>
        <city>La Plata</city>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 032010</name>
      <address>
        <city>Ramos Mejia</city>
        <zip>B1704ETD</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 032013</name>
      <address>
        <city>Rosario</city>
        <zip>S2000PBJ</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 032004</name>
      <address>
        <city>San Miguel De Tucuman</city>
        <zip>T4000AXL</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 032009</name>
      <address>
        <city>Zarate</city>
        <zip>B2800DGH</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 036014</name>
      <address>
        <city>Victoria Park</city>
        <zip>6100</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 040004</name>
      <address>
        <city>Stockerau</city>
        <zip>2000</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 040003</name>
      <address>
        <city>Wien</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 076001</name>
      <address>
        <city>Curitiba</city>
        <zip>80060-240</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 076016</name>
      <address>
        <city>Curitiba</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 076006</name>
      <address>
        <city>Goiania</city>
        <zip>74110-120</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 076010</name>
      <address>
        <city>Juiz De Fora</city>
        <zip>36010-570</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 076005</name>
      <address>
        <city>Rio De Janeiro</city>
        <zip>20551-030</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 076015</name>
      <address>
        <city>Rio De Janeiro</city>
        <zip>22271-100</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 124005</name>
      <address>
        <city>Toronto</city>
        <zip>M5T 2S8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 124009</name>
      <address>
        <city>Trois-Rivières</city>
        <zip>G8Z 1Y2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 124104</name>
      <address>
        <city>Victoria</city>
        <zip>V8V 3P9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 152015</name>
      <address>
        <city>Temuco</city>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 170001</name>
      <address>
        <city>Bogota</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 170012</name>
      <address>
        <city>Bogota</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 170006</name>
      <address>
        <city>Bogotá</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 170007</name>
      <address>
        <city>Bucaramanga</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 170009</name>
      <address>
        <city>Bucaramanga</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 170014</name>
      <address>
        <city>Chia</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 170019</name>
      <address>
        <city>Medellin</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 203008</name>
      <address>
        <city>Hostivice</city>
        <zip>233 01</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 203004</name>
      <address>
        <city>Ostrava</city>
        <zip>702 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 203007</name>
      <address>
        <city>Praha 2</city>
        <zip>12850</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 203002</name>
      <address>
        <city>Uherske Hradiste</city>
        <zip>686 01</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 203006</name>
      <address>
        <city>Zlin</city>
        <zip>76001</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 218003</name>
      <address>
        <city>Cuenca</city>
        <country>Ecuador</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 218001</name>
      <address>
        <city>Guayaquil</city>
        <zip>0593</zip>
        <country>Ecuador</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 218002</name>
      <address>
        <city>Quito</city>
        <zip>0593</zip>
        <country>Ecuador</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 276011</name>
      <address>
        <city>Bad Nauheim</city>
        <zip>61231</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 276010</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 276001</name>
      <address>
        <city>Berlin</city>
        <zip>12305</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 276014</name>
      <address>
        <city>Berlin</city>
        <zip>14059</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 276018</name>
      <address>
        <city>Deggingen</city>
        <zip>73326</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 276004</name>
      <address>
        <city>Erlangen</city>
        <zip>91054</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 276015</name>
      <address>
        <city>Halle/Saale</city>
        <zip>06108</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 276013</name>
      <address>
        <city>Hamburg</city>
        <zip>22147</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 276016</name>
      <address>
        <city>Leipzig</city>
        <zip>04103</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 276017</name>
      <address>
        <city>München</city>
        <zip>80336</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 276021</name>
      <address>
        <city>Osnabrück</city>
        <zip>49074</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 276020</name>
      <address>
        <city>Tübingen</city>
        <zip>72076</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 276019</name>
      <address>
        <city>Zerbst</city>
        <zip>39261</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 300002</name>
      <address>
        <city>Heraklion</city>
        <zip>71110</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 300005</name>
      <address>
        <city>Thessaloniki</city>
        <zip>57010</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 320002</name>
      <address>
        <city>Guatemala City</city>
        <zip>01009</zip>
        <country>Guatemala</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 320003</name>
      <address>
        <city>Guatemala City</city>
        <zip>01011</zip>
        <country>Guatemala</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 320001</name>
      <address>
        <city>Guatemala City</city>
        <zip>09090</zip>
        <country>Guatemala</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 348022</name>
      <address>
        <city>Budapest</city>
        <zip>1036</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 348003</name>
      <address>
        <city>Debrecen</city>
        <zip>4032</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 348004</name>
      <address>
        <city>Veszprém</city>
        <zip>8200</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 348017</name>
      <address>
        <city>Veszprém</city>
        <zip>8200</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 376001</name>
      <address>
        <city>Haifa</city>
        <zip>31048</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 376003</name>
      <address>
        <city>Petach Tikva</city>
        <zip>49100</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 376002</name>
      <address>
        <city>Tel Hashomer</city>
        <zip>52621</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 380011</name>
      <address>
        <city>Catania</city>
        <zip>95122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 380002</name>
      <address>
        <city>Firenze</city>
        <zip>50139</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 380005</name>
      <address>
        <city>Genova</city>
        <zip>16132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 380014</name>
      <address>
        <city>Milano</city>
        <zip>20157</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 380013</name>
      <address>
        <city>Udine</city>
        <zip>33100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 410017</name>
      <address>
        <city>Daejeon</city>
        <zip>301-721</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 410016</name>
      <address>
        <city>Seoul</city>
        <zip>120-752</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 440005</name>
      <address>
        <city>Kaunas</city>
        <zip>LT-50009</zip>
        <country>Lithuania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 440006</name>
      <address>
        <city>Klaipeda</city>
        <zip>LT-92288</zip>
        <country>Lithuania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 440007</name>
      <address>
        <city>Vilnius</city>
        <zip>LT-08661</zip>
        <country>Lithuania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 484023</name>
      <address>
        <city>Chihuahua</city>
        <zip>31020</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 484018</name>
      <address>
        <city>Guadalajara</city>
        <zip>44620</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 484002</name>
      <address>
        <city>Guadalajara</city>
        <zip>44690</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 484024</name>
      <address>
        <city>Guadalajara</city>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 484010</name>
      <address>
        <city>Mexicali</city>
        <zip>21200</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 484019</name>
      <address>
        <city>Monterrey</city>
        <zip>64000</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 484020</name>
      <address>
        <city>Monterrey</city>
        <zip>64000</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 484005</name>
      <address>
        <city>Monterrey</city>
        <zip>64460</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 484017</name>
      <address>
        <city>México</city>
        <zip>06700</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 484021</name>
      <address>
        <city>Queretaro</city>
        <zip>76178</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 554005</name>
      <address>
        <city>Hamilton</city>
        <zip>3204</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 554011</name>
      <address>
        <city>Nelson</city>
        <zip>7010</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 554007</name>
      <address>
        <city>Otahuhu</city>
        <zip>2025</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 554001</name>
      <address>
        <city>Timaru</city>
        <zip>7910</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 554006</name>
      <address>
        <city>Wellington</city>
        <zip>6021</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 604010</name>
      <address>
        <city>Lima</city>
        <zip>14</zip>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 604009</name>
      <address>
        <city>Lima</city>
        <zip>LIMA 01</zip>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 604006</name>
      <address>
        <city>Lima</city>
        <zip>LIMA 11</zip>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 604012</name>
      <address>
        <city>Lima</city>
        <zip>LIMA 11</zip>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 604013</name>
      <address>
        <city>Lima</city>
        <zip>LIMA 13</zip>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 604001</name>
      <address>
        <city>Lima</city>
        <zip>Lima 21</zip>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 604008</name>
      <address>
        <city>Lima</city>
        <zip>LIMA 27</zip>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 604007</name>
      <address>
        <city>Lima</city>
        <zip>Lima 33</zip>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 604005</name>
      <address>
        <city>Lima</city>
        <zip>LIMA 41</zip>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 604014</name>
      <address>
        <city>Lima</city>
        <zip>LIMA 41</zip>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 616014</name>
      <address>
        <city>Bialystok</city>
        <zip>15-099</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 616019</name>
      <address>
        <city>Bydgoszcz</city>
        <zip>85-168</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 616015</name>
      <address>
        <city>Elblag</city>
        <zip>82-300</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 616018</name>
      <address>
        <city>Poznan</city>
        <zip>61-397</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 616016</name>
      <address>
        <city>Szczecin</city>
        <zip>71-252</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 616004</name>
      <address>
        <city>Warszawa</city>
        <zip>02-118</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 616017</name>
      <address>
        <city>Warszawa</city>
        <zip>02-653</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 616020</name>
      <address>
        <city>Wroclaw</city>
        <zip>50-556</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 620002</name>
      <address>
        <city>Lisboa</city>
        <zip>1050-034</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 620004</name>
      <address>
        <city>Lisboa</city>
        <zip>1649-035</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 620007</name>
      <address>
        <city>Ponte De Lima</city>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 642001</name>
      <address>
        <city>Bucuresti</city>
        <zip>010976</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 642012</name>
      <address>
        <city>Bucuresti</city>
        <zip>020475</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 642002</name>
      <address>
        <city>Bucuresti</city>
        <zip>020983</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 642014</name>
      <address>
        <city>Iasi</city>
        <zip>700661</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 643001</name>
      <address>
        <city>Moscow</city>
        <zip>115522</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 643021</name>
      <address>
        <city>Moscow</city>
        <zip>119049</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 643022</name>
      <address>
        <city>Novosibirsk</city>
        <zip>630091</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 643008</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>192242</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 643010</name>
      <address>
        <city>Samara</city>
        <zip>443095</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 703001</name>
      <address>
        <city>Kosice</city>
        <zip>040 11</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 724016</name>
      <address>
        <city>Barakaldo</city>
        <zip>48903</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 724015</name>
      <address>
        <city>Barcelona</city>
        <zip>08034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 724014</name>
      <address>
        <city>Cadiz</city>
        <zip>1009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 724009</name>
      <address>
        <city>La Coruña</city>
        <zip>15006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 724001</name>
      <address>
        <city>Málaga</city>
        <zip>29009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 724011</name>
      <address>
        <city>Sabadell</city>
        <zip>08208</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 724017</name>
      <address>
        <city>Santiago De Compostela</city>
        <zip>15702</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 724013</name>
      <address>
        <city>Santiago De Compostela</city>
        <zip>15706</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 724007</name>
      <address>
        <city>Sevilla</city>
        <zip>41071</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 158005</name>
      <address>
        <city>Kaohsiung</city>
        <zip>81346</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 158006</name>
      <address>
        <city>Taipei</city>
        <zip>402</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 158002</name>
      <address>
        <city>Taoyuan County</city>
        <zip>33305</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 792007</name>
      <address>
        <city>Edirne</city>
        <zip>22030</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 792008</name>
      <address>
        <city>Gaziantep</city>
        <zip>27310</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 792009</name>
      <address>
        <city>Samsun</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 804013</name>
      <address>
        <city>Kharkiv</city>
        <zip>61176</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 804014</name>
      <address>
        <city>Kyiv</city>
        <zip>01103</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 804027</name>
      <address>
        <city>Kyiv</city>
        <zip>03680</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 804011</name>
      <address>
        <city>Vinnytsia</city>
        <zip>21018</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 804009</name>
      <address>
        <city>Zaporizhzhya</city>
        <zip>69600</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Australia</country>
    <country>Austria</country>
    <country>Brazil</country>
    <country>Canada</country>
    <country>Chile</country>
    <country>Colombia</country>
    <country>Czechia</country>
    <country>Ecuador</country>
    <country>Germany</country>
    <country>Greece</country>
    <country>Guatemala</country>
    <country>Hungary</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Korea, Republic of</country>
    <country>Lithuania</country>
    <country>Mexico</country>
    <country>New Zealand</country>
    <country>Peru</country>
    <country>Poland</country>
    <country>Portugal</country>
    <country>Romania</country>
    <country>Russian Federation</country>
    <country>Slovakia</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>Turkey</country>
    <country>Ukraine</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Czech Republic</country>
    <country>Hong Kong</country>
  </removed_countries>
  <results_reference>
    <citation>Fleischmann R, van Adelsberg J, Lin Y, Castelar-Pinheiro GD, Brzezicki J, Hrycaj P, Graham NM, van Hoogstraten H, Bauer D, Burmester GR. Sarilumab and Nonbiologic Disease-Modifying Antirheumatic Drugs in Patients With Active Rheumatoid Arthritis and Inadequate Response or Intolerance to Tumor Necrosis Factor Inhibitors. Arthritis Rheumatol. 2017 Feb;69(2):277-290. doi: 10.1002/art.39944.</citation>
    <PMID>27860410</PMID>
  </results_reference>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>October 15, 2012</study_first_submitted>
  <study_first_submitted_qc>October 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 18, 2012</study_first_posted>
  <results_first_submitted>May 23, 2017</results_first_submitted>
  <results_first_submitted_qc>July 7, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">August 8, 2017</results_first_posted>
  <disposition_first_submitted>November 16, 2015</disposition_first_submitted>
  <disposition_first_submitted_qc>November 16, 2015</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">December 14, 2015</disposition_first_posted>
  <last_update_submitted>July 7, 2017</last_update_submitted>
  <last_update_submitted_qc>July 7, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 8, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthritis</mesh_term>
    <mesh_term>Arthritis, Rheumatoid</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hydroxychloroquine</mesh_term>
    <mesh_term>Sulfasalazine</mesh_term>
    <mesh_term>Methotrexate</mesh_term>
    <mesh_term>Leflunomide</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was conducted at 240 centers in 27 countries. A total of 1224 participants were screened between 29 October 2012 and 7 August 2014, of whom 546 participants were randomized and 678 were screen failures. Screen failures were mainly due to failure to meet inclusion criteria.</recruitment_details>
      <pre_assignment_details>Participants were randomized 1:1:1 (placebo q2w : sarilumab 150 mg q2w : sarilumab 200 mg q2w) via a centralized randomization system using an interactive voice response system stratified by region and number of previous anti- tumor necrosis factor (TNF) therapy (1 versus &gt;1).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo q2w</title>
          <description>Placebo matched to sarilumab subcutaneous (SC) injection once every 2 weeks (q2w) was added to one or a combination of the nonbiologic disease modifying antirheumatic drug (DMARD) for 24 weeks.</description>
        </group>
        <group group_id="P2">
          <title>Sarilumab 150 mg q2w</title>
          <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
        </group>
        <group group_id="P3">
          <title>Sarilumab 200 mg q2w</title>
          <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="181"/>
                <participants group_id="P2" count="181"/>
                <participants group_id="P3" count="184"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="101"/>
                <participants group_id="P2" count="125"/>
                <participants group_id="P3" count="133"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="80"/>
                <participants group_id="P2" count="56"/>
                <participants group_id="P3" count="51"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Rescued and entered in long term safety</title>
              <participants_list>
                <participants group_id="P1" count="63"/>
                <participants group_id="P2" count="25"/>
                <participants group_id="P3" count="26"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="18"/>
                <participants group_id="P3" count="17"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Poor compliance to protocol</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other, not related to safety or efficacy</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Placebo q2w</title>
          <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
        </group>
        <group group_id="B2">
          <title>Sarilumab 150 mg q2w</title>
          <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
        </group>
        <group group_id="B3">
          <title>Sarilumab 200 mg q2w</title>
          <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="181"/>
            <count group_id="B2" value="181"/>
            <count group_id="B3" value="184"/>
            <count group_id="B4" value="546"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="51.9" spread="12.4"/>
                    <measurement group_id="B2" value="54.0" spread="11.7"/>
                    <measurement group_id="B3" value="52.9" spread="12.9"/>
                    <measurement group_id="B4" value="52.9" spread="12.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="154"/>
                    <measurement group_id="B2" value="142"/>
                    <measurement group_id="B3" value="151"/>
                    <measurement group_id="B4" value="447"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="39"/>
                    <measurement group_id="B3" value="33"/>
                    <measurement group_id="B4" value="99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants Who Achieved at Least 20% Improvement in the American College of Rheumatology (ACR20) Criteria at Week 24</title>
        <description>ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: tender joint count (TJC); swollen joint count (SJC); levels of an acute phase reactant (C-reactive Protein levels [CRP]); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by (health assessment questionnaire disability index [HAQ-DI]). ACR20 is defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments of the ACR.</description>
        <time_frame>Week 24</time_frame>
        <population>Intent-to-treat (ITT) population included all randomized participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Achieved at Least 20% Improvement in the American College of Rheumatology (ACR20) Criteria at Week 24</title>
          <description>ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: tender joint count (TJC); swollen joint count (SJC); levels of an acute phase reactant (C-reactive Protein levels [CRP]); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by (health assessment questionnaire disability index [HAQ-DI]). ACR20 is defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments of the ACR.</description>
          <population>Intent-to-treat (ITT) population included all randomized participants.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="181"/>
                <count group_id="O2" value="181"/>
                <count group_id="O3" value="184"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.7"/>
                    <measurement group_id="O2" value="55.8"/>
                    <measurement group_id="O3" value="60.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A hierarchical testing procedure was used to control type I error rate at 0.05 and handle multiple endpoint analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when previous endpoint was statistically significant at 0.025 level.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance at 0.025 level</p_value_desc>
            <method>Mantel Haenszel</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>2.711</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.730</ci_lower_limit>
            <ci_upper_limit>4.247</ci_upper_limit>
            <estimate_desc>Sarilumab 150 mg q2w vs Placebo q2w</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance at 0.025 level</p_value_desc>
            <method>Mantel Haenszel</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>3.284</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>2.108</ci_lower_limit>
            <ci_upper_limit>5.115</ci_upper_limit>
            <estimate_desc>Sarilumab 200 mg q2w vs Placebo q2w</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12</title>
        <description>Physical function was assessed by HAQ-DI. It consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. Least-squares (LS) means and standard errors (SE) at Week 12 were obtained from a mixed-effect model with repeated measures (MMRM) with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline HAQ-DI as a covariate.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>ITT population. Number of participants analyzed = number of participants with HAQ-DI assessment at both baseline and Week 12.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12</title>
          <description>Physical function was assessed by HAQ-DI. It consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. Least-squares (LS) means and standard errors (SE) at Week 12 were obtained from a mixed-effect model with repeated measures (MMRM) with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline HAQ-DI as a covariate.</description>
          <population>ITT population. Number of participants analyzed = number of participants with HAQ-DI assessment at both baseline and Week 12.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="170"/>
                <count group_id="O2" value="165"/>
                <count group_id="O3" value="171"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.26" spread="0.043"/>
                    <measurement group_id="O2" value="-0.46" spread="0.044"/>
                    <measurement group_id="O3" value="-0.47" spread="0.043"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0007</p_value>
            <p_value_desc>Threshold for significance at 0.025 level</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.202</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.318</ci_lower_limit>
            <ci_upper_limit>-0.086</ci_upper_limit>
            <estimate_desc>Sarilumab 150 mg q2w vs Placebo q2w</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0004</p_value>
            <p_value_desc>Threshold for significance at 0.025 level</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.210</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.325</ci_lower_limit>
            <ci_upper_limit>-0.095</ci_upper_limit>
            <estimate_desc>Sarilumab 200 mg q2w vs Placebo q2w</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Disease Activity Score for 28 Joints -C-Reactive Protein (DAS28--CRP) Score at Week 24</title>
        <description>DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); General health (GH) assessment by the participant assessed from the ACR rheumatoid arthritis (RA) core set questionnaire (participant global assessment) in 100 mm visual analog scale (VAS). Marker of inflammation assessed by the high sensitivity C-reactive protein (hs-CRP) in mg/L. The DAS28 score provides a number indicating the current disease activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline DAS28-CRP score as a covariate.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>ITT population. Number of participants analyzed = number of participants with DAS28--CRP Score assessment at both baseline and Week 24.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Disease Activity Score for 28 Joints -C-Reactive Protein (DAS28--CRP) Score at Week 24</title>
          <description>DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); General health (GH) assessment by the participant assessed from the ACR rheumatoid arthritis (RA) core set questionnaire (participant global assessment) in 100 mm visual analog scale (VAS). Marker of inflammation assessed by the high sensitivity C-reactive protein (hs-CRP) in mg/L. The DAS28 score provides a number indicating the current disease activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline DAS28-CRP score as a covariate.</description>
          <population>ITT population. Number of participants analyzed = number of participants with DAS28--CRP Score assessment at both baseline and Week 24.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="99"/>
                <count group_id="O2" value="126"/>
                <count group_id="O3" value="136"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.38" spread="0.119"/>
                    <measurement group_id="O2" value="-2.35" spread="0.111"/>
                    <measurement group_id="O3" value="-2.82" spread="0.108"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance at 0.025 level</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.971</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.283</ci_lower_limit>
            <ci_upper_limit>-0.658</ci_upper_limit>
            <estimate_desc>Sarilumab 150 mg q2w vs Placebo q2w</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance at 0.025 level</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-1.444</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.752</ci_lower_limit>
            <ci_upper_limit>-1.135</ci_upper_limit>
            <estimate_desc>Sarilumab 200 mg q2w vs Placebo q2w</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Achieving ACR50 Criteria at Week 24</title>
        <description>ACR responses are assessed with a composite rating scale that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR50 is defined as achieving at least 50% improvement in both TJC and SJC, and at least 50% improvement in at least 3 of the 5 other assessments of the ACR.</description>
        <time_frame>Week 24</time_frame>
        <population>ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving ACR50 Criteria at Week 24</title>
          <description>ACR responses are assessed with a composite rating scale that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR50 is defined as achieving at least 50% improvement in both TJC and SJC, and at least 50% improvement in at least 3 of the 5 other assessments of the ACR.</description>
          <population>ITT population.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="181"/>
                <count group_id="O2" value="181"/>
                <count group_id="O3" value="184"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.2"/>
                    <measurement group_id="O2" value="37.0"/>
                    <measurement group_id="O3" value="40.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance at 0.025 level</p_value_desc>
            <method>Mantel Haenszel</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>2.958</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.764</ci_lower_limit>
            <ci_upper_limit>4.959</ci_upper_limit>
            <estimate_desc>Sarilumab 150 mg q2w vs Placebo q2w</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance was 0.025 level</p_value_desc>
            <method>Mantel Haenszel</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>3.374</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>2.045</ci_lower_limit>
            <ci_upper_limit>5.566</ci_upper_limit>
            <estimate_desc>Sarilumab 200 mg q2w vs Placebo q2w</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Achieving ACR70 Criteria at Week 24</title>
        <description>ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR70 is defined as achieving at least 70% improvement in both TJC and SJC, and at least 70% improvement in at least 3 of the 5 other assessments of the ACR.</description>
        <time_frame>Week 24</time_frame>
        <population>ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving ACR70 Criteria at Week 24</title>
          <description>ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR70 is defined as achieving at least 70% improvement in both TJC and SJC, and at least 70% improvement in at least 3 of the 5 other assessments of the ACR.</description>
          <population>ITT population.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="181"/>
                <count group_id="O2" value="181"/>
                <count group_id="O3" value="184"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.2"/>
                    <measurement group_id="O2" value="19.9"/>
                    <measurement group_id="O3" value="16.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0002</p_value>
            <p_value_desc>Threshold for significance at 0.025 level</p_value_desc>
            <method>Mantel Haenszel</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>3.607</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.774</ci_lower_limit>
            <ci_upper_limit>7.332</ci_upper_limit>
            <estimate_desc>Sarilumab 150 mg q2w vs Placebo q2w</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0056</p_value>
            <p_value_desc>Threshold for significance at 0.025 level</p_value_desc>
            <method>Mantel Haenszel</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>2.653</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.308</ci_lower_limit>
            <ci_upper_limit>5.383</ci_upper_limit>
            <estimate_desc>Sarilumab 200 mg q2w vs Placebo q2w</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP) &lt;2.6 at Week 24</title>
        <description>DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR rheumatoid arthritis core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission.</description>
        <time_frame>Week 24</time_frame>
        <population>ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP) &lt;2.6 at Week 24</title>
          <description>DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR rheumatoid arthritis core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission.</description>
          <population>ITT population.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="181"/>
                <count group_id="O2" value="181"/>
                <count group_id="O3" value="184"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.2"/>
                    <measurement group_id="O2" value="24.9"/>
                    <measurement group_id="O3" value="28.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance at 0.025 level</p_value_desc>
            <method>Mantel Haenszel</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>4.622</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>2.339</ci_lower_limit>
            <ci_upper_limit>9.132</ci_upper_limit>
            <estimate_desc>Sarilumab 150 mg q2w vs Placebo q2w</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance at 0.025 level</p_value_desc>
            <method>Mantel Haenszel</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>5.801</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>2.948</ci_lower_limit>
            <ci_upper_limit>11.413</ci_upper_limit>
            <estimate_desc>Sarilumab 200 mg q2w vs Placebo q2w</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24</title>
        <description>CDAI is a composite index constructed to measure clinical remission in RA that does not include a laboratory test, and is a numerical summation of 4 components: TJC (28 joints), SJC (28 joints), Participant's Global Assessment of Disease Activity VAS (in cm), and Physician's Global Assessment of Disease VAS (in cm). Total scores ranges from 0 to 76 with a negative change in CDAI score indicating an improvement in disease activity and a positive change in score indicating a worsening of disease activity. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline CDAI as a covariate.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>ITT population. Number of participants analyzed=number of participants with CDAI assessment at both baseline and Week 24.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24</title>
          <description>CDAI is a composite index constructed to measure clinical remission in RA that does not include a laboratory test, and is a numerical summation of 4 components: TJC (28 joints), SJC (28 joints), Participant's Global Assessment of Disease Activity VAS (in cm), and Physician's Global Assessment of Disease VAS (in cm). Total scores ranges from 0 to 76 with a negative change in CDAI score indicating an improvement in disease activity and a positive change in score indicating a worsening of disease activity. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline CDAI as a covariate.</description>
          <population>ITT population. Number of participants analyzed=number of participants with CDAI assessment at both baseline and Week 24.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="127"/>
                <count group_id="O3" value="136"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-16.35" spread="1.195"/>
                    <measurement group_id="O2" value="-23.65" spread="1.136"/>
                    <measurement group_id="O3" value="-26.08" spread="1.109"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance at 0.025 level</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-7.306</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-10.444</ci_lower_limit>
            <ci_upper_limit>-4.167</ci_upper_limit>
            <estimate_desc>Sarilumab 150 mg q2w vs Placebo q2w</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance at 0.025 level</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-9.727</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-12.833</ci_lower_limit>
            <ci_upper_limit>-6.622</ci_upper_limit>
            <estimate_desc>Sarilumab 200 mg q2w vs Placebo q2w</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in HAQ-DI at Week 24</title>
        <description>Physical function was assessed by HAQ-DI. It consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline HAQ-DI as a covariate.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>ITT population. Number of participants analyzed = number of participants with HAQ-DI assessment at both baseline and Week 24.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in HAQ-DI at Week 24</title>
          <description>Physical function was assessed by HAQ-DI. It consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline HAQ-DI as a covariate.</description>
          <population>ITT population. Number of participants analyzed = number of participants with HAQ-DI assessment at both baseline and Week 24.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="101"/>
                <count group_id="O2" value="127"/>
                <count group_id="O3" value="136"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.34" spread="0.051"/>
                    <measurement group_id="O2" value="-0.52" spread="0.049"/>
                    <measurement group_id="O3" value="-0.58" spread="0.048"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0078</p_value>
            <p_value_desc>Threshold for significance was 0.025 level</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.183</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.318</ci_lower_limit>
            <ci_upper_limit>-0.048</ci_upper_limit>
            <estimate_desc>Sarilumab 150 mg q2w vs Placebo q2w</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0004</p_value>
            <p_value_desc>Threshold for significance was 0.025 level</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.242</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.376</ci_lower_limit>
            <ci_upper_limit>-0.109</ci_upper_limit>
            <estimate_desc>Sarilumab 200 mg q2w vs Placebo q2w</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Physical Component Summary Scores (PCS) at Week 24</title>
        <description>SF-36 is a generic 36-item questionnaire measuring health-related quality of life (HRQL) covering 2 summary measures: PCS and mental component summary (MCS). The SF-36 consists of 8 subscales. The PCS had 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS had 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 24 by MMRM with treatment,region,number of previous anti TNFs,visit,and treatment-by-visit interaction as fixed effects and baseline SF-36 (PCS) as a covariate.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>ITT population. Number of participants analyzed = participants with SF-36 PCS assessment at both baseline and Week 24.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Physical Component Summary Scores (PCS) at Week 24</title>
          <description>SF-36 is a generic 36-item questionnaire measuring health-related quality of life (HRQL) covering 2 summary measures: PCS and mental component summary (MCS). The SF-36 consists of 8 subscales. The PCS had 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS had 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 24 by MMRM with treatment,region,number of previous anti TNFs,visit,and treatment-by-visit interaction as fixed effects and baseline SF-36 (PCS) as a covariate.</description>
          <population>ITT population. Number of participants analyzed = participants with SF-36 PCS assessment at both baseline and Week 24.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="99"/>
                <count group_id="O2" value="123"/>
                <count group_id="O3" value="134"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.40" spread="0.692"/>
                    <measurement group_id="O2" value="7.65" spread="0.653"/>
                    <measurement group_id="O3" value="8.48" spread="0.630"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0004</p_value>
            <p_value_desc>Threshold for significance at 0.025 level</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>3.250</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.450</ci_lower_limit>
            <ci_upper_limit>5.049</ci_upper_limit>
            <estimate_desc>Sarilumab 150 mg q2w vs Placebo q2w</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance at 0.025 level</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>4.075</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>2.305</ci_lower_limit>
            <ci_upper_limit>5.846</ci_upper_limit>
            <estimate_desc>Sarilumab 200 mg q2w vs Placebo q2w</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in SF-36 MCS at Week 24</title>
        <description>SF-36 is a generic 36-item questionnaire measuring HRQL covering 2 summary measures: PCS and MCS. The SF-36 consists of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline SF-36 MCS as a covariate.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>ITT population. Number of participants analyzed=participants with SF-36 MCS assessment at both baseline and Week 24.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in SF-36 MCS at Week 24</title>
          <description>SF-36 is a generic 36-item questionnaire measuring HRQL covering 2 summary measures: PCS and MCS. The SF-36 consists of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline SF-36 MCS as a covariate.</description>
          <population>ITT population. Number of participants analyzed=participants with SF-36 MCS assessment at both baseline and Week 24.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="99"/>
                <count group_id="O2" value="123"/>
                <count group_id="O3" value="134"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.74" spread="0.902"/>
                    <measurement group_id="O2" value="6.26" spread="0.848"/>
                    <measurement group_id="O3" value="6.76" spread="0.817"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.2026</p_value>
            <p_value_desc>Threshold for significance at 0.025 level</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>1.515</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.818</ci_lower_limit>
            <ci_upper_limit>3.848</ci_upper_limit>
            <estimate_desc>Sarilumab 150 mg q2w vs Placebo q2w</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0854</p_value>
            <p_value_desc>Threshold for significance at 0.025 level</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>2.013</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.282</ci_lower_limit>
            <ci_upper_limit>4.309</ci_upper_limit>
            <estimate_desc>Sarilumab 200 mg q2w vs Placebo q2w</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-fatigue) Score at Week 24</title>
        <description>The FACIT-Fatigue is a 13-item questionnaire assessing fatigue where participants scored each item on a 5-point scale (0-4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. A total score ranging from 0 to 52. A higher score corresponded to a lower level of fatigue. A positive change from baseline score indicates an improvement. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline FACIT-fatigue as a covariate.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>ITT population. Number of Participants analyzed = number of participants with FACIT-fatigue score assessment at both baseline and Week 24.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-fatigue) Score at Week 24</title>
          <description>The FACIT-Fatigue is a 13-item questionnaire assessing fatigue where participants scored each item on a 5-point scale (0-4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. A total score ranging from 0 to 52. A higher score corresponded to a lower level of fatigue. A positive change from baseline score indicates an improvement. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline FACIT-fatigue as a covariate.</description>
          <population>ITT population. Number of Participants analyzed = number of participants with FACIT-fatigue score assessment at both baseline and Week 24.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="98"/>
                <count group_id="O2" value="126"/>
                <count group_id="O3" value="136"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.82" spread="0.863"/>
                    <measurement group_id="O2" value="9.86" spread="0.802"/>
                    <measurement group_id="O3" value="10.06" spread="0.778"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Morning Stiffness VAS at Week 24</title>
        <description>RA is associated with stiffness of joints, especially in the morning after prolonged stationery state. The degree of stiffness can be an indicator of disease severity. The severity of morning stiffness was assessed on a VAS scale from 0 mm (no problem) to 100 mm (major problem). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline Morning Stiffness as a covariate.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>ITT population. Number of participants analyzed = number of participants with morning stiffness VAS assessment at both baseline and Week 24.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Morning Stiffness VAS at Week 24</title>
          <description>RA is associated with stiffness of joints, especially in the morning after prolonged stationery state. The degree of stiffness can be an indicator of disease severity. The severity of morning stiffness was assessed on a VAS scale from 0 mm (no problem) to 100 mm (major problem). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline Morning Stiffness as a covariate.</description>
          <population>ITT population. Number of participants analyzed = number of participants with morning stiffness VAS assessment at both baseline and Week 24.</population>
          <units>mm</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="101"/>
                <count group_id="O2" value="127"/>
                <count group_id="O3" value="136"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-21.66" spread="2.390"/>
                    <measurement group_id="O2" value="-32.30" spread="2.213"/>
                    <measurement group_id="O3" value="-33.79" spread="2.148"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Week 24: Work Days Missed Due to RA</title>
        <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days missed in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>ITT population. Number of participants analyzed=participants with WPS-RA individual items assessment at both baseline and Week 24.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Week 24: Work Days Missed Due to RA</title>
          <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days missed in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
          <population>ITT population. Number of participants analyzed=participants with WPS-RA individual items assessment at both baseline and Week 24.</population>
          <units>Days</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="43"/>
                <count group_id="O3" value="45"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.01" spread="0.458"/>
                    <measurement group_id="O2" value="-2.87" spread="0.438"/>
                    <measurement group_id="O3" value="-3.19" spread="0.447"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in WPS-RA at Week 24: Days With Work Productivity Reduced by ≥ 50% Due to RA</title>
        <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days with reduced productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in WPS-RA at Week 24: Days With Work Productivity Reduced by ≥ 50% Due to RA</title>
          <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days with reduced productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
          <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.</population>
          <units>Days</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="43"/>
                <count group_id="O3" value="45"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.64" spread="0.589"/>
                    <measurement group_id="O2" value="-4.26" spread="0.521"/>
                    <measurement group_id="O3" value="-4.34" spread="0.535"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in WPS-RA at Week 24: RA Interference With Work Productivity</title>
        <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Interference in the last month with work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in WPS-RA at Week 24: RA Interference With Work Productivity</title>
          <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Interference in the last month with work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
          <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="42"/>
                <count group_id="O3" value="45"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.632" spread="0.4186"/>
                    <measurement group_id="O2" value="-2.422" spread="0.3719"/>
                    <measurement group_id="O3" value="-2.727" spread="0.3700"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to RA</title>
        <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with no household work in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to RA</title>
          <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with no household work in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
          <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.</population>
          <units>Days</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="101"/>
                <count group_id="O2" value="126"/>
                <count group_id="O3" value="133"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.50" spread="0.590"/>
                    <measurement group_id="O2" value="-6.13" spread="0.551"/>
                    <measurement group_id="O3" value="-6.18" spread="0.537"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in WPS-RA at Week 24: Days With Household Work Productivity Reduced by ≥ 50% Due to RA</title>
        <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with reduced household work productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in WPS-RA at Week 24: Days With Household Work Productivity Reduced by ≥ 50% Due to RA</title>
          <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with reduced household work productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
          <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.</population>
          <units>Days</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="101"/>
                <count group_id="O2" value="125"/>
                <count group_id="O3" value="133"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.36" spread="0.632"/>
                    <measurement group_id="O2" value="-4.60" spread="0.591"/>
                    <measurement group_id="O3" value="-4.88" spread="0.574"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in WPS-RA at Week 24: Days With Family/Social/Leisure Activities Missed Due to RA</title>
        <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days missed of family/social/leisure activities in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in WPS-RA at Week 24: Days With Family/Social/Leisure Activities Missed Due to RA</title>
          <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days missed of family/social/leisure activities in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
          <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.</population>
          <units>Days</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="101"/>
                <count group_id="O2" value="127"/>
                <count group_id="O3" value="133"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.97" spread="0.479"/>
                    <measurement group_id="O2" value="-3.51" spread="0.446"/>
                    <measurement group_id="O3" value="-4.12" spread="0.435"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to RA</title>
        <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with outside help hired in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to RA</title>
          <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with outside help hired in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
          <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.</population>
          <units>Days</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="101"/>
                <count group_id="O2" value="126"/>
                <count group_id="O3" value="133"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.60" spread="0.567"/>
                    <measurement group_id="O2" value="-3.87" spread="0.536"/>
                    <measurement group_id="O3" value="-3.86" spread="0.523"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in WPS-RA at Week 24: RA Interference With Household Work Productivity</title>
        <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). The RA interference in the last month with household work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in WPS-RA at Week 24: RA Interference With Household Work Productivity</title>
          <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). The RA interference in the last month with household work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
          <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="126"/>
                <count group_id="O3" value="132"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.970" spread="0.2438"/>
                    <measurement group_id="O2" value="-3.096" spread="0.2238"/>
                    <measurement group_id="O3" value="-3.269" spread="0.2186"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Scores at Week 24</title>
        <description>RAID is a composite measure of the impact of RA on participants that takes into account 7 domains: pain, functional disability, fatigue, physical and emotional well being, quality of sleep, and coping. The RAID is calculated based on 7 numerical rating scales (NRS) questions. Range of the final RAID value is 0-10 where 0= not affected, very good and 10 = most affected weighted and calculated with a total score range of 0 (not affected, very good) to 10 (most affected). A higher RAID value indicate worse status and lower indicate not affected. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline RAID as a covariate.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>ITT population. Number of participants analyzed = number of participants with RAID score assessment at both baseline and Week 24.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Scores at Week 24</title>
          <description>RAID is a composite measure of the impact of RA on participants that takes into account 7 domains: pain, functional disability, fatigue, physical and emotional well being, quality of sleep, and coping. The RAID is calculated based on 7 numerical rating scales (NRS) questions. Range of the final RAID value is 0-10 where 0= not affected, very good and 10 = most affected weighted and calculated with a total score range of 0 (not affected, very good) to 10 (most affected). A higher RAID value indicate worse status and lower indicate not affected. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline RAID as a covariate.</description>
          <population>ITT population. Number of participants analyzed = number of participants with RAID score assessment at both baseline and Week 24.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="99"/>
                <count group_id="O2" value="126"/>
                <count group_id="O3" value="136"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.80" spread="0.203"/>
                    <measurement group_id="O2" value="-2.55" spread="0.189"/>
                    <measurement group_id="O3" value="-2.80" spread="0.183"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in European Quality of Life-5 Dimension 3 Level (EQ-5D-3L) VAS Scores at Week 24</title>
        <description>The EQ-5D-3L is a standardized, generic measure of health outcome. It was designed for self-completion by participants. It was specifically included to address concerns regarding the health economic impact of RA. The EQ-5D-3L comprises 5 questions on mobility, self-care, pain, usual activities, and psychological status with 3 possible answers for each item (1=no problem, 2=moderate problems, 3=severe problems) and a vertical VAS that allows the participants to indicate their health state today that can range from 0 (worst imaginable) to 100 (best imaginable). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline EQ-5D-3L Scores as a covariate.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>ITT population. Number of participants analyzed = number of participants with EQ-5D-3L score assessment at both baseline and Week 24.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in European Quality of Life-5 Dimension 3 Level (EQ-5D-3L) VAS Scores at Week 24</title>
          <description>The EQ-5D-3L is a standardized, generic measure of health outcome. It was designed for self-completion by participants. It was specifically included to address concerns regarding the health economic impact of RA. The EQ-5D-3L comprises 5 questions on mobility, self-care, pain, usual activities, and psychological status with 3 possible answers for each item (1=no problem, 2=moderate problems, 3=severe problems) and a vertical VAS that allows the participants to indicate their health state today that can range from 0 (worst imaginable) to 100 (best imaginable). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline EQ-5D-3L Scores as a covariate.</description>
          <population>ITT population. Number of participants analyzed = number of participants with EQ-5D-3L score assessment at both baseline and Week 24.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="96"/>
                <count group_id="O2" value="126"/>
                <count group_id="O3" value="133"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.85" spread="2.098"/>
                    <measurement group_id="O2" value="20.06" spread="1.891"/>
                    <measurement group_id="O3" value="18.40" spread="1.842"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Achieving ACR20, ACR50 and ACR70 Criteria at Week 12</title>
        <description>ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR20 is defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments of the ACR. ACR50 is defined as achieving at least 50% improvement in both TJC and SJC, and at least 50% improvement in at least 3 of the 5 other assessments of the ACR. ACR70 is defined as achieving at least 70% improvement in both TJC and SJC, and at least 70% improvement in at least 3 of the 5 other assessments of the ACR.</description>
        <time_frame>Week 12</time_frame>
        <population>ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving ACR20, ACR50 and ACR70 Criteria at Week 12</title>
          <description>ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR20 is defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments of the ACR. ACR50 is defined as achieving at least 50% improvement in both TJC and SJC, and at least 50% improvement in at least 3 of the 5 other assessments of the ACR. ACR70 is defined as achieving at least 70% improvement in both TJC and SJC, and at least 70% improvement in at least 3 of the 5 other assessments of the ACR.</description>
          <population>ITT population.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="181"/>
                <count group_id="O2" value="181"/>
                <count group_id="O3" value="184"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>ACR20</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37.6"/>
                    <measurement group_id="O2" value="54.1"/>
                    <measurement group_id="O3" value="62.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ACR50</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.3"/>
                    <measurement group_id="O2" value="30.4"/>
                    <measurement group_id="O3" value="33.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ACR70</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.2"/>
                    <measurement group_id="O2" value="13.8"/>
                    <measurement group_id="O3" value="14.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in DAS28-CRP at Week 12</title>
        <description>DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR rheumatoid arthritis core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline DAS score as a covariate.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>ITT population. Number of participants analyzed = number of participants with DAS28-CRP- Score assessment at both baseline and Week 12.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in DAS28-CRP at Week 12</title>
          <description>DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR rheumatoid arthritis core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline DAS score as a covariate.</description>
          <population>ITT population. Number of participants analyzed = number of participants with DAS28-CRP- Score assessment at both baseline and Week 12.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="168"/>
                <count group_id="O2" value="163"/>
                <count group_id="O3" value="169"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.97" spread="0.104"/>
                    <measurement group_id="O2" value="-2.13" spread="0.105"/>
                    <measurement group_id="O3" value="-2.45" spread="0.103"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Achieving Clinical Remission Score (DAS28--CRP &lt;2.6) at Week 12</title>
        <description>DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR RA core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission.</description>
        <time_frame>Week 12</time_frame>
        <population>ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving Clinical Remission Score (DAS28--CRP &lt;2.6) at Week 12</title>
          <description>DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR RA core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission.</description>
          <population>ITT population.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="181"/>
                <count group_id="O2" value="181"/>
                <count group_id="O3" value="184"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.9"/>
                    <measurement group_id="O2" value="17.1"/>
                    <measurement group_id="O3" value="17.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in SF-36 at Week 12</title>
        <description>SF-36 is a generic 36-item questionnaire measuring HRQL covering 2 summary measures: PCS and MCS. The SF-36 consists of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline SF-36 as a covariate.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>ITT population. Number of participants analyzed=participants with SF-36 assessment at both baseline and Week 12.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in SF-36 at Week 12</title>
          <description>SF-36 is a generic 36-item questionnaire measuring HRQL covering 2 summary measures: PCS and MCS. The SF-36 consists of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline SF-36 as a covariate.</description>
          <population>ITT population. Number of participants analyzed=participants with SF-36 assessment at both baseline and Week 12.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="169"/>
                <count group_id="O2" value="160"/>
                <count group_id="O3" value="165"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Physical Component Summary Score at Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.74" spread="0.582"/>
                    <measurement group_id="O2" value="6.93" spread="0.596"/>
                    <measurement group_id="O3" value="6.84" spread="0.584"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mental Component Summary Score at Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.50" spread="0.738"/>
                    <measurement group_id="O2" value="5.14" spread="0.758"/>
                    <measurement group_id="O3" value="6.47" spread="0.741"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in WPS-RA at Week 12: Work Days Missed Due to RA</title>
        <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days missed in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>ITT population. Number of participants analyzed=participants with WPS-RA individual items assessment at both baseline and Week 12.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in WPS-RA at Week 12: Work Days Missed Due to RA</title>
          <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days missed in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
          <population>ITT population. Number of participants analyzed=participants with WPS-RA individual items assessment at both baseline and Week 12.</population>
          <units>Days</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="54"/>
                <count group_id="O2" value="54"/>
                <count group_id="O3" value="56"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.20" spread="0.581"/>
                    <measurement group_id="O2" value="-1.97" spread="0.571"/>
                    <measurement group_id="O3" value="-2.98" spread="0.585"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in WPS-RA at Week 12: Days With Work Productivity Reduced by ≥ 50% Due to RA</title>
        <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days with reduced productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in WPS-RA at Week 12: Days With Work Productivity Reduced by ≥ 50% Due to RA</title>
          <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days with reduced productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
          <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.</population>
          <units>Days</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="54"/>
                <count group_id="O2" value="54"/>
                <count group_id="O3" value="56"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.69" spread="0.784"/>
                    <measurement group_id="O2" value="-4.24" spread="0.773"/>
                    <measurement group_id="O3" value="-3.20" spread="0.785"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in WPS-RA at Week 12: RA Interference With Work Productivity</title>
        <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Interference in the last month with work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in WPS-RA at Week 12: RA Interference With Work Productivity</title>
          <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Interference in the last month with work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
          <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="53"/>
                <count group_id="O2" value="54"/>
                <count group_id="O3" value="56"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.043" spread="0.3803"/>
                    <measurement group_id="O2" value="-1.924" spread="0.3742"/>
                    <measurement group_id="O3" value="-1.873" spread="0.3764"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in WPS-RA at Week 12: House Work Days Missed Due to RA</title>
        <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with no household work in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in WPS-RA at Week 12: House Work Days Missed Due to RA</title>
          <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with no household work in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
          <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.</population>
          <units>Days</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="170"/>
                <count group_id="O2" value="164"/>
                <count group_id="O3" value="169"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.10" spread="0.551"/>
                    <measurement group_id="O2" value="-5.52" spread="0.563"/>
                    <measurement group_id="O3" value="-5.54" spread="0.553"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in WPS-RA at Week 12: Days With Household Work Productivity Reduced by ≥ 50% Due to RA</title>
        <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with reduced household work productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in WPS-RA at Week 12: Days With Household Work Productivity Reduced by ≥ 50% Due to RA</title>
          <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with reduced household work productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
          <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.</population>
          <units>Days</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="169"/>
                <count group_id="O2" value="163"/>
                <count group_id="O3" value="169"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.60" spread="0.576"/>
                    <measurement group_id="O2" value="-3.97" spread="0.587"/>
                    <measurement group_id="O3" value="-3.98" spread="0.575"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in WPS-RA at Week 12: Days With Family/Social/Leisure Activities Missed Due to RA</title>
        <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days missed of family/social/leisure activities in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in WPS-RA at Week 12: Days With Family/Social/Leisure Activities Missed Due to RA</title>
          <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days missed of family/social/leisure activities in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
          <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.</population>
          <units>Days</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="170"/>
                <count group_id="O2" value="164"/>
                <count group_id="O3" value="169"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.23" spread="0.433"/>
                    <measurement group_id="O2" value="-2.53" spread="0.442"/>
                    <measurement group_id="O3" value="-3.26" spread="0.434"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in WPS-RA at Week 12: Days With Outside Help Hired Due to RA</title>
        <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with outside help hired in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in WPS-RA at Week 12: Days With Outside Help Hired Due to RA</title>
          <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with outside help hired in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
          <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.</population>
          <units>Days</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="170"/>
                <count group_id="O2" value="164"/>
                <count group_id="O3" value="169"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.77" spread="0.558"/>
                    <measurement group_id="O2" value="-3.07" spread="0.570"/>
                    <measurement group_id="O3" value="-2.94" spread="0.560"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in WPS-RA at Week 12: RA Interference With Household Work Productivity</title>
        <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). The RA interference in the last month with household work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in WPS-RA at Week 12: RA Interference With Household Work Productivity</title>
          <description>The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). The RA interference in the last month with household work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.</description>
          <population>ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="169"/>
                <count group_id="O2" value="164"/>
                <count group_id="O3" value="167"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.210" spread="0.2428"/>
                    <measurement group_id="O2" value="-2.772" spread="0.2474"/>
                    <measurement group_id="O3" value="-2.404" spread="0.2443"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the FACIT-fatigue at Week 12</title>
        <description>The FACIT-Fatigue is a 13-item questionnaire assessing fatigue where participants scored each item on a 5-point scale (0-4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. A total score ranging from 0 to 52. A higher score corresponded to a lower level of fatigue. A positive change from baseline score indicates an improvement. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline FACIT-fatigue as a covariate.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>ITT population. Number of Participants analyzed = number of participants with FACIT-fatigue score assessment at both baseline and Week 12.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the FACIT-fatigue at Week 12</title>
          <description>The FACIT-Fatigue is a 13-item questionnaire assessing fatigue where participants scored each item on a 5-point scale (0-4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. A total score ranging from 0 to 52. A higher score corresponded to a lower level of fatigue. A positive change from baseline score indicates an improvement. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline FACIT-fatigue as a covariate.</description>
          <population>ITT population. Number of Participants analyzed = number of participants with FACIT-fatigue score assessment at both baseline and Week 12.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="169"/>
                <count group_id="O2" value="165"/>
                <count group_id="O3" value="172"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.56" spread="0.721"/>
                    <measurement group_id="O2" value="8.02" spread="0.729"/>
                    <measurement group_id="O3" value="9.45" spread="0.714"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in EQ-5D-3L VAS Scores at Week 12</title>
        <description>The EQ-5D-3L is a standardized, generic measure of health outcome. EQ-5D was designed for self-completion by participants. The EQ-5D was specifically included to address concerns regarding the health economic impact of RA. The EQ-5D-3L comprises 5 questions on mobility, self-care, pain, usual activities, and psychological status with 3 possible answers for each item (1=no problem, 2=moderate problems, 3=severe problems) and a vertical VAS that allows the participants to indicate their health state today that can range from 0 (worst imaginable) to 100 (best imaginable). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline EQ-5D-3L scores as a covariate.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>ITT population. Number of participants analyzed = number of participants with EQ-5D-3L score assessment at both baseline and Week 12.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in EQ-5D-3L VAS Scores at Week 12</title>
          <description>The EQ-5D-3L is a standardized, generic measure of health outcome. EQ-5D was designed for self-completion by participants. The EQ-5D was specifically included to address concerns regarding the health economic impact of RA. The EQ-5D-3L comprises 5 questions on mobility, self-care, pain, usual activities, and psychological status with 3 possible answers for each item (1=no problem, 2=moderate problems, 3=severe problems) and a vertical VAS that allows the participants to indicate their health state today that can range from 0 (worst imaginable) to 100 (best imaginable). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline EQ-5D-3L scores as a covariate.</description>
          <population>ITT population. Number of participants analyzed = number of participants with EQ-5D-3L score assessment at both baseline and Week 12.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="167"/>
                <count group_id="O2" value="163"/>
                <count group_id="O3" value="171"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.39" spread="1.699"/>
                    <measurement group_id="O2" value="17.16" spread="1.720"/>
                    <measurement group_id="O3" value="15.23" spread="1.680"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in RAID Scores at Week 12</title>
        <description>RAID score is a composite measure of the impact of RA on participants that takes into account 7 domains: pain, functional disability, fatigue, physical and emotional well being, quality of sleep, and coping. The RAID is calculated based on 7 NRS questions. Range of the final RAID value is 0-10 where 0= not affected, very good and 10 = most affected weighted and calculated with a total score range of 0 (not affected, very good) to 10 (most affected). A higher RAID value indicates worse status and lower indicates not affected. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline RAID scores as a covariate.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>ITT population. Number of participants analyzed = number of participants with RAID score assessment at both baseline and Week 12.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in RAID Scores at Week 12</title>
          <description>RAID score is a composite measure of the impact of RA on participants that takes into account 7 domains: pain, functional disability, fatigue, physical and emotional well being, quality of sleep, and coping. The RAID is calculated based on 7 NRS questions. Range of the final RAID value is 0-10 where 0= not affected, very good and 10 = most affected weighted and calculated with a total score range of 0 (not affected, very good) to 10 (most affected). A higher RAID value indicates worse status and lower indicates not affected. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline RAID scores as a covariate.</description>
          <population>ITT population. Number of participants analyzed = number of participants with RAID score assessment at both baseline and Week 12.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="167"/>
                <count group_id="O2" value="162"/>
                <count group_id="O3" value="171"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.34" spread="0.163"/>
                    <measurement group_id="O2" value="-2.27" spread="0.165"/>
                    <measurement group_id="O3" value="-2.47" spread="0.161"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Individual ACR Components - TJC and SJC at Week 12 and Week 24</title>
        <description>ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS,HAQ-DI &amp; CRP. 68 joints were assessed for tenderness (TJC scoring 0-68) and 66 joints for swelling (SJC scoring 0-66). The 66 SJC evaluated the following joints: temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, interphalangeal of thumb, distal interphalangeal, proximal interphalangeal, knee, ankle mortise, ankle tarsus, metatarsophalangeal, interphalangeal of great toe, and proximal/distal interphalangeal of the toes. The TJC examined hip joints, in addition to the joints assessed for SJC. Increase in number of tender joints/swollen joints indicated severity. LS mean and SE at Week 12 &amp; 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.</description>
        <time_frame>Baseline, Week 12 and Week 24</time_frame>
        <population>ITT population. Number analyzed = number of participants with TJC and SJC assessments at both baseline and specified time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Individual ACR Components - TJC and SJC at Week 12 and Week 24</title>
          <description>ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS,HAQ-DI &amp; CRP. 68 joints were assessed for tenderness (TJC scoring 0-68) and 66 joints for swelling (SJC scoring 0-66). The 66 SJC evaluated the following joints: temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, interphalangeal of thumb, distal interphalangeal, proximal interphalangeal, knee, ankle mortise, ankle tarsus, metatarsophalangeal, interphalangeal of great toe, and proximal/distal interphalangeal of the toes. The TJC examined hip joints, in addition to the joints assessed for SJC. Increase in number of tender joints/swollen joints indicated severity. LS mean and SE at Week 12 &amp; 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.</description>
          <population>ITT population. Number analyzed = number of participants with TJC and SJC assessments at both baseline and specified time points.</population>
          <units>joints</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="181"/>
                <count group_id="O2" value="181"/>
                <count group_id="O3" value="184"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TJC at week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="172"/>
                    <count group_id="O2" value="165"/>
                    <count group_id="O3" value="172"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.55" spread="0.959"/>
                    <measurement group_id="O2" value="-13.74" spread="0.975"/>
                    <measurement group_id="O3" value="-14.87" spread="0.954"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SJC at week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="172"/>
                    <count group_id="O2" value="165"/>
                    <count group_id="O3" value="172"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.75" spread="0.687"/>
                    <measurement group_id="O2" value="-10.54" spread="0.698"/>
                    <measurement group_id="O3" value="-10.59" spread="0.684"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TJC at week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="101"/>
                    <count group_id="O2" value="127"/>
                    <count group_id="O3" value="137"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.55" spread="1.060"/>
                    <measurement group_id="O2" value="-14.44" spread="1.017"/>
                    <measurement group_id="O3" value="-16.95" spread="0.992"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SJC at week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="101"/>
                    <count group_id="O2" value="127"/>
                    <count group_id="O3" value="137"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.19" spread="0.721"/>
                    <measurement group_id="O2" value="-11.56" spread="0.691"/>
                    <measurement group_id="O3" value="-11.94" spread="0.674"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 12 and Week 24</title>
        <description>ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI &amp; CRP. Physician global VAS &amp; participant global VAS was done by 100 mm non-anchored VAS, from no arthritis (0) activity to maximal arthritis (100) activity. Pain VAS by 100 mm VAS ranging from 0 &quot;no pain&quot; to 100 &quot;worst pain&quot;. LS mean and SE at Week 12 &amp; 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.</description>
        <time_frame>Baseline, Week 12 and Week 24</time_frame>
        <population>ITT population. Number analyzed = number of participants with individual ACR components assessment at both baseline and specified time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 12 and Week 24</title>
          <description>ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI &amp; CRP. Physician global VAS &amp; participant global VAS was done by 100 mm non-anchored VAS, from no arthritis (0) activity to maximal arthritis (100) activity. Pain VAS by 100 mm VAS ranging from 0 &quot;no pain&quot; to 100 &quot;worst pain&quot;. LS mean and SE at Week 12 &amp; 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.</description>
          <population>ITT population. Number analyzed = number of participants with individual ACR components assessment at both baseline and specified time points.</population>
          <units>mm</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="181"/>
                <count group_id="O2" value="181"/>
                <count group_id="O3" value="184"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Physician global VAS at week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="172"/>
                    <count group_id="O2" value="165"/>
                    <count group_id="O3" value="171"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-22.74" spread="1.744"/>
                    <measurement group_id="O2" value="-33.64" spread="1.775"/>
                    <measurement group_id="O3" value="-35.44" spread="1.740"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participant global VAS at week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="172"/>
                    <count group_id="O2" value="165"/>
                    <count group_id="O3" value="171"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-13.75" spread="1.807"/>
                    <measurement group_id="O2" value="-25.28" spread="1.836"/>
                    <measurement group_id="O3" value="-27.38" spread="1.803"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain VAS at week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="171"/>
                    <count group_id="O2" value="166"/>
                    <count group_id="O3" value="171"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.13" spread="1.908"/>
                    <measurement group_id="O2" value="-26.93" spread="1.933"/>
                    <measurement group_id="O3" value="-30.56" spread="1.901"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physician global VAS at week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="101"/>
                    <count group_id="O2" value="127"/>
                    <count group_id="O3" value="137"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-28.55" spread="1.806"/>
                    <measurement group_id="O2" value="-40.65" spread="1.695"/>
                    <measurement group_id="O3" value="-43.22" spread="1.646"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participant global VAS at week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                    <count group_id="O2" value="127"/>
                    <count group_id="O3" value="136"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-19.76" spread="2.171"/>
                    <measurement group_id="O2" value="-29.59" spread="2.046"/>
                    <measurement group_id="O3" value="-31.28" spread="1.997"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain VAS at week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="98"/>
                    <count group_id="O2" value="127"/>
                    <count group_id="O3" value="135"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-21.27" spread="2.250"/>
                    <measurement group_id="O2" value="-31.90" spread="2.086"/>
                    <measurement group_id="O3" value="-33.65" spread="2.037"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Individual ACR Component - CRP Level at Week 12 and Week 24</title>
        <description>ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI &amp; CRP. An elevated CRP level was considered a non-specific &quot;marker&quot; for RA. A reduction level indicates improvement. LS mean and SE at Week 12 &amp; 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.</description>
        <time_frame>Baseline, Week 12 and Week 24</time_frame>
        <population>ITT population. Number analyzed = number of participants with CRP assessment at both baseline and specified time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Individual ACR Component - CRP Level at Week 12 and Week 24</title>
          <description>ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI &amp; CRP. An elevated CRP level was considered a non-specific &quot;marker&quot; for RA. A reduction level indicates improvement. LS mean and SE at Week 12 &amp; 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.</description>
          <population>ITT population. Number analyzed = number of participants with CRP assessment at both baseline and specified time points.</population>
          <units>mg/L</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="181"/>
                <count group_id="O2" value="181"/>
                <count group_id="O3" value="184"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>CRP at week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="168"/>
                    <count group_id="O2" value="165"/>
                    <count group_id="O3" value="170"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.63" spread="1.436"/>
                    <measurement group_id="O2" value="-15.08" spread="1.452"/>
                    <measurement group_id="O3" value="-22.98" spread="1.432"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CRP at week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                    <count group_id="O2" value="126"/>
                    <count group_id="O3" value="137"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.60" spread="1.556"/>
                    <measurement group_id="O2" value="-15.24" spread="1.457"/>
                    <measurement group_id="O3" value="-23.27" spread="1.421"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Individual ACR Component - HAQ-DI at Week 12 and Week 24</title>
        <description>ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS,HAQ-DI &amp; CRP. HAQ-DI consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. LS mean and SE at Week 12 &amp; 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.</description>
        <time_frame>Baseline, Week 12 and Week 24</time_frame>
        <population>ITT population. Number analyzed = number of participants with HAQ-DI assessment at both baseline and specified time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo q2w</title>
            <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sarilumab 150 mg q2w</title>
            <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Sarilumab 200 mg q2w</title>
            <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Individual ACR Component - HAQ-DI at Week 12 and Week 24</title>
          <description>ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS,HAQ-DI &amp; CRP. HAQ-DI consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. LS mean and SE at Week 12 &amp; 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.</description>
          <population>ITT population. Number analyzed = number of participants with HAQ-DI assessment at both baseline and specified time points.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="181"/>
                <count group_id="O2" value="181"/>
                <count group_id="O3" value="184"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>HAQ-DI at week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="170"/>
                    <count group_id="O2" value="165"/>
                    <count group_id="O3" value="171"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.26" spread="0.043"/>
                    <measurement group_id="O2" value="-0.46" spread="0.044"/>
                    <measurement group_id="O3" value="-0.47" spread="0.043"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HAQ-DI at week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="101"/>
                    <count group_id="O2" value="127"/>
                    <count group_id="O3" value="136"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.34" spread="0.051"/>
                    <measurement group_id="O2" value="-0.52" spread="0.049"/>
                    <measurement group_id="O3" value="-0.58" spread="0.048"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product.</time_frame>
      <desc>Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo q2w</title>
          <description>Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
        </group>
        <group group_id="E2">
          <title>Sarilumab 150 mg q2w</title>
          <description>Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
        </group>
        <group group_id="E3">
          <title>Sarilumab 200 mg q2w</title>
          <description>Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 17.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="184"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="184"/>
              </event>
              <event>
                <sub_title>Atrioventricular block second degree</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="184"/>
              </event>
              <event>
                <sub_title>Endocarditis noninfective</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastric ulcer haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="184"/>
              </event>
              <event>
                <sub_title>Inguinal hernia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Mixed liver injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bacteraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="184"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="184"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="184"/>
              </event>
              <event>
                <sub_title>Osteomyelitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="184"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Ankle fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="184"/>
              </event>
              <event>
                <sub_title>Post procedural haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="184"/>
              </event>
              <event>
                <sub_title>Road traffic accident</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="184"/>
              </event>
              <event>
                <sub_title>Transaminases increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Intervertebral disc disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="184"/>
              </event>
              <event>
                <sub_title>Intervertebral disc protrusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="184"/>
              </event>
              <event>
                <sub_title>Rheumatoid arthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Ureteric cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Ischaemic stroke</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="184"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Venous thrombosis limb</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 17.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="26" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="60" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="57" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="22" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Injection site erythema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="184"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertriglyceridaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="181"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="181"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="184"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Trial Transparency Team</name_or_title>
      <organization>Sanofi</organization>
      <email>Contact-US@sanofi.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01709578
org study id: EFC10832
secondary id: U1111-1115-8466
secondary id: 2011-003538-16
nct id: NCT01709578
lead sponsor: 
collaborator: 
has dmc: Yes
Primary Objective:

      To demonstrate that sarilumab added to disease modifying anti-rheumatic drugs (DMARDs) were
      effective for:

        -  reduction of signs and symptoms at Week 24 and

        -  improvement of physical function at Week 12

      in participants with active rheumatoid arthritis (RA) who were inadequate responders or
      intolerant to tumor necrosis factor alpha (TNF-α) antagonists.

      Secondary Objectives:

      The secondary objectives were to investigate the effects of SAR153191 (REGN88) when added to
      DMARD therapy, in participants with active RA who were inadequate responders or intolerant to
      TNF-α antagonists, for:

        -  Reduction of signs and symptoms at Week 12;

        -  Improvement in physical function at Week 24;

        -  Improvement in disease activity score as measured by other American College of
           Rheumatology (ACR) derived components at Weeks 12 and 24;

        -  Improvement in quality of life as measured by participant reported outcomes (PROs) at
           intermediate visits and Week 24.

      To assess the exposure of sarilumab added to DMARD therapy in this population.

      To assess the safety of sarilumab in this population.
Total study duration was up to 34 weeks: screening up to 28 days, treatment phase of 24
      weeks, and post-treatment follow-up of 6 weeks.

      After completion of the treatment phase of this study, participant were eligible to enter a
      long term safety study (LTS11210) for active treatment with SAR153191 (REGN88).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percentage of Participants Who Achieved at Least 20% Improvement in the American College of Rheumatology (ACR20) Criteria at Week 24
time frame: Week 24
description: ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: tender joint count (TJC); swollen joint count (SJC); levels of an acute phase reactant (C-reactive Protein levels [CRP]); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by (health assessment questionnaire disability index [HAQ-DI]). ACR20 is defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments of the ACR.
measure: Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12
time frame: Baseline, Week 12
description: Physical function was assessed by HAQ-DI. It consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. Least-squares (LS) means and standard errors (SE) at Week 12 were obtained from a mixed-effect model with repeated measures (MMRM) with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline HAQ-DI as a covariate.
measure: Change From Baseline in Disease Activity Score for 28 Joints -C-Reactive Protein (DAS28--CRP) Score at Week 24
time frame: Baseline, Week 24
description: DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); General health (GH) assessment by the participant assessed from the ACR rheumatoid arthritis (RA) core set questionnaire (participant global assessment) in 100 mm visual analog scale (VAS). Marker of inflammation assessed by the high sensitivity C-reactive protein (hs-CRP) in mg/L. The DAS28 score provides a number indicating the current disease activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline DAS28-CRP score as a covariate.
measure: Percentage of Participants Achieving ACR50 Criteria at Week 24
time frame: Week 24
description: ACR responses are assessed with a composite rating scale that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR50 is defined as achieving at least 50% improvement in both TJC and SJC, and at least 50% improvement in at least 3 of the 5 other assessments of the ACR.
measure: Percentage of Participants Achieving ACR70 Criteria at Week 24
time frame: Week 24
description: ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR70 is defined as achieving at least 70% improvement in both TJC and SJC, and at least 70% improvement in at least 3 of the 5 other assessments of the ACR.
measure: Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP) <2.6 at Week 24
time frame: Week 24
description: DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR rheumatoid arthritis core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission.
measure: Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24
time frame: Baseline, Week 24
description: CDAI is a composite index constructed to measure clinical remission in RA that does not include a laboratory test, and is a numerical summation of 4 components: TJC (28 joints), SJC (28 joints), Participant's Global Assessment of Disease Activity VAS (in cm), and Physician's Global Assessment of Disease VAS (in cm). Total scores ranges from 0 to 76 with a negative change in CDAI score indicating an improvement in disease activity and a positive change in score indicating a worsening of disease activity. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline CDAI as a covariate.
measure: Change From Baseline in HAQ-DI at Week 24
time frame: Baseline, Week 24
description: Physical function was assessed by HAQ-DI. It consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline HAQ-DI as a covariate.
measure: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Physical Component Summary Scores (PCS) at Week 24
time frame: Baseline, Week 24
description: SF-36 is a generic 36-item questionnaire measuring health-related quality of life (HRQL) covering 2 summary measures: PCS and mental component summary (MCS). The SF-36 consists of 8 subscales. The PCS had 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS had 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 24 by MMRM with treatment,region,number of previous anti TNFs,visit,and treatment-by-visit interaction as fixed effects and baseline SF-36 (PCS) as a covariate.
measure: Change From Baseline in SF-36 MCS at Week 24
time frame: Baseline, Week 24
description: SF-36 is a generic 36-item questionnaire measuring HRQL covering 2 summary measures: PCS and MCS. The SF-36 consists of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline SF-36 MCS as a covariate.
measure: Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-fatigue) Score at Week 24
time frame: Baseline, Week 24
description: The FACIT-Fatigue is a 13-item questionnaire assessing fatigue where participants scored each item on a 5-point scale (0-4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. A total score ranging from 0 to 52. A higher score corresponded to a lower level of fatigue. A positive change from baseline score indicates an improvement. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline FACIT-fatigue as a covariate.
measure: Change From Baseline in Morning Stiffness VAS at Week 24
time frame: Baseline, Week 24
description: RA is associated with stiffness of joints, especially in the morning after prolonged stationery state. The degree of stiffness can be an indicator of disease severity. The severity of morning stiffness was assessed on a VAS scale from 0 mm (no problem) to 100 mm (major problem). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline Morning Stiffness as a covariate.
measure: Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Week 24: Work Days Missed Due to RA
time frame: Baseline, Week 24
description: The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days missed in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
measure: Change From Baseline in WPS-RA at Week 24: Days With Work Productivity Reduced by ≥ 50% Due to RA
time frame: Baseline, Week 24
description: The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days with reduced productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
measure: Change From Baseline in WPS-RA at Week 24: RA Interference With Work Productivity
time frame: Baseline, Week 24
description: The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Interference in the last month with work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
measure: Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to RA
time frame: Baseline, Week 24
description: The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with no household work in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
measure: Change From Baseline in WPS-RA at Week 24: Days With Household Work Productivity Reduced by ≥ 50% Due to RA
time frame: Baseline, Week 24
description: The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with reduced household work productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
measure: Change From Baseline in WPS-RA at Week 24: Days With Family/Social/Leisure Activities Missed Due to RA
time frame: Baseline, Week 24
description: The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days missed of family/social/leisure activities in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
measure: Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to RA
time frame: Baseline, Week 24
description: The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with outside help hired in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
measure: Change From Baseline in WPS-RA at Week 24: RA Interference With Household Work Productivity
time frame: Baseline, Week 24
description: The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). The RA interference in the last month with household work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
measure: Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Scores at Week 24
time frame: Baseline, Week 24
description: RAID is a composite measure of the impact of RA on participants that takes into account 7 domains: pain, functional disability, fatigue, physical and emotional well being, quality of sleep, and coping. The RAID is calculated based on 7 numerical rating scales (NRS) questions. Range of the final RAID value is 0-10 where 0= not affected, very good and 10 = most affected weighted and calculated with a total score range of 0 (not affected, very good) to 10 (most affected). A higher RAID value indicate worse status and lower indicate not affected. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline RAID as a covariate.
measure: Change From Baseline in European Quality of Life-5 Dimension 3 Level (EQ-5D-3L) VAS Scores at Week 24
time frame: Baseline, Week 24
description: The EQ-5D-3L is a standardized, generic measure of health outcome. It was designed for self-completion by participants. It was specifically included to address concerns regarding the health economic impact of RA. The EQ-5D-3L comprises 5 questions on mobility, self-care, pain, usual activities, and psychological status with 3 possible answers for each item (1=no problem, 2=moderate problems, 3=severe problems) and a vertical VAS that allows the participants to indicate their health state today that can range from 0 (worst imaginable) to 100 (best imaginable). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline EQ-5D-3L Scores as a covariate.
measure: Percentage of Participants Achieving ACR20, ACR50 and ACR70 Criteria at Week 12
time frame: Week 12
description: ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR20 is defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments of the ACR. ACR50 is defined as achieving at least 50% improvement in both TJC and SJC, and at least 50% improvement in at least 3 of the 5 other assessments of the ACR. ACR70 is defined as achieving at least 70% improvement in both TJC and SJC, and at least 70% improvement in at least 3 of the 5 other assessments of the ACR.
measure: Change From Baseline in DAS28-CRP at Week 12
time frame: Baseline, Week 12
description: DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR rheumatoid arthritis core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline DAS score as a covariate.
measure: Percentage of Participants Achieving Clinical Remission Score (DAS28--CRP <2.6) at Week 12
time frame: Week 12
description: DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR RA core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission.
measure: Change From Baseline in SF-36 at Week 12
time frame: Baseline, Week 12
description: SF-36 is a generic 36-item questionnaire measuring HRQL covering 2 summary measures: PCS and MCS. The SF-36 consists of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline SF-36 as a covariate.
measure: Change From Baseline in WPS-RA at Week 12: Work Days Missed Due to RA
time frame: Baseline, Week 12
description: The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days missed in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
measure: Change From Baseline in WPS-RA at Week 12: Days With Work Productivity Reduced by ≥ 50% Due to RA
time frame: Baseline, Week 12
description: The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days with reduced productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
measure: Change From Baseline in WPS-RA at Week 12: RA Interference With Work Productivity
time frame: Baseline, Week 12
description: The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Interference in the last month with work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
measure: Change From Baseline in WPS-RA at Week 12: House Work Days Missed Due to RA
time frame: Baseline, Week 12
description: The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with no household work in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
measure: Change From Baseline in WPS-RA at Week 12: Days With Household Work Productivity Reduced by ≥ 50% Due to RA
time frame: Baseline, Week 12
description: The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with reduced household work productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
measure: Change From Baseline in WPS-RA at Week 12: Days With Family/Social/Leisure Activities Missed Due to RA
time frame: Baseline, Week 12
description: The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days missed of family/social/leisure activities in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
measure: Change From Baseline in WPS-RA at Week 12: Days With Outside Help Hired Due to RA
time frame: Baseline, Week 12
description: The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with outside help hired in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
measure: Change From Baseline in WPS-RA at Week 12: RA Interference With Household Work Productivity
time frame: Baseline, Week 12
description: The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). The RA interference in the last month with household work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.
measure: Change From Baseline in the FACIT-fatigue at Week 12
time frame: Baseline, Week 12
description: The FACIT-Fatigue is a 13-item questionnaire assessing fatigue where participants scored each item on a 5-point scale (0-4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. A total score ranging from 0 to 52. A higher score corresponded to a lower level of fatigue. A positive change from baseline score indicates an improvement. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline FACIT-fatigue as a covariate.
measure: Change From Baseline in EQ-5D-3L VAS Scores at Week 12
time frame: Baseline, Week 12
description: The EQ-5D-3L is a standardized, generic measure of health outcome. EQ-5D was designed for self-completion by participants. The EQ-5D was specifically included to address concerns regarding the health economic impact of RA. The EQ-5D-3L comprises 5 questions on mobility, self-care, pain, usual activities, and psychological status with 3 possible answers for each item (1=no problem, 2=moderate problems, 3=severe problems) and a vertical VAS that allows the participants to indicate their health state today that can range from 0 (worst imaginable) to 100 (best imaginable). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline EQ-5D-3L scores as a covariate.
measure: Change From Baseline in RAID Scores at Week 12
time frame: Baseline, Week 12
description: RAID score is a composite measure of the impact of RA on participants that takes into account 7 domains: pain, functional disability, fatigue, physical and emotional well being, quality of sleep, and coping. The RAID is calculated based on 7 NRS questions. Range of the final RAID value is 0-10 where 0= not affected, very good and 10 = most affected weighted and calculated with a total score range of 0 (not affected, very good) to 10 (most affected). A higher RAID value indicates worse status and lower indicates not affected. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline RAID scores as a covariate.
measure: Change From Baseline in Individual ACR Components - TJC and SJC at Week 12 and Week 24
time frame: Baseline, Week 12 and Week 24
description: ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS,HAQ-DI & CRP. 68 joints were assessed for tenderness (TJC scoring 0-68) and 66 joints for swelling (SJC scoring 0-66). The 66 SJC evaluated the following joints: temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, interphalangeal of thumb, distal interphalangeal, proximal interphalangeal, knee, ankle mortise, ankle tarsus, metatarsophalangeal, interphalangeal of great toe, and proximal/distal interphalangeal of the toes. The TJC examined hip joints, in addition to the joints assessed for SJC. Increase in number of tender joints/swollen joints indicated severity. LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.
measure: Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 12 and Week 24
time frame: Baseline, Week 12 and Week 24
description: ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & CRP. Physician global VAS & participant global VAS was done by 100 mm non-anchored VAS, from no arthritis (0) activity to maximal arthritis (100) activity. Pain VAS by 100 mm VAS ranging from 0 "no pain" to 100 "worst pain". LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.
measure: Change From Baseline in Individual ACR Component - CRP Level at Week 12 and Week 24
time frame: Baseline, Week 12 and Week 24
description: ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & CRP. An elevated CRP level was considered a non-specific "marker" for RA. A reduction level indicates improvement. LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.
measure: Change From Baseline in Individual ACR Component - HAQ-DI at Week 12 and Week 24
time frame: Baseline, Week 12 and Week 24
description: ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS,HAQ-DI & CRP. HAQ-DI consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.
arm group label: Placebo q2w
arm group type: Placebo Comparator
description: Placebo matched to sarilumab once every 2 weeks (q2w) was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks.
arm group label: Sarilumab 150 mg q2w
arm group type: Experimental
description: Sarilumab 150 mg q2w was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks.
arm group label: Sarilumab 200 mg q2w
arm group type: Experimental
description: Sarilumab 200 mg q2w was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks.
intervention type: Drug
intervention name: Sarilumab
description: Pharmaceutical form:solution Route of administration: subcutaneous
arm group label: Sarilumab 150 mg q2w
arm group label: Sarilumab 200 mg q2w
other name: SAR153191
other name: REGN88
intervention type: Drug
intervention name: placebo
description: Pharmaceutical form:solution Route of administration: subcutaneous
arm group label: Placebo q2w
intervention type: Drug
intervention name: hydroxychloroquine
description: Dispensed according to the local practice.
arm group label: Placebo q2w
arm group label: Sarilumab 150 mg q2w
arm group label: Sarilumab 200 mg q2w
intervention type: Drug
intervention name: methotrexate
description: Dispensed according to the local practice.
arm group label: Placebo q2w
arm group label: Sarilumab 150 mg q2w
arm group label: Sarilumab 200 mg q2w
intervention type: Drug
intervention name: sulfasalazine
description: Dispensed according to the local practice.
arm group label: Placebo q2w
arm group label: Sarilumab 150 mg q2w
arm group label: Sarilumab 200 mg q2w
intervention type: Drug
intervention name: leflunomide
description: Dispensed according to the local practice.
arm group label: Placebo q2w
arm group label: Sarilumab 150 mg q2w
arm group label: Sarilumab 200 mg q2w
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Sciences & Operations
role: Study Director
affiliation: Sanofi
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country: Argentina
country: Australia
country: Austria
country: Brazil
country: Canada
country: Chile
country: Colombia
country: Czechia
country: Ecuador
country: Germany
country: Greece
country: Guatemala
country: Hungary
country: Israel
country: Italy
country: Korea, Republic of
country: Lithuania
country: Mexico
country: New Zealand
country: Peru
country: Poland
country: Portugal
country: Romania
country: Russian Federation
country: Slovakia
country: Spain
country: Taiwan
country: Turkey
country: Ukraine
country: United States
country: Czech Republic
country: Hong Kong
citation: Fleischmann R, van Adelsberg J, Lin Y, Castelar-Pinheiro GD, Brzezicki J, Hrycaj P, Graham NM, van Hoogstraten H, Bauer D, Burmester GR. Sarilumab and Nonbiologic Disease-Modifying Antirheumatic Drugs in Patients With Active Rheumatoid Arthritis and Inadequate Response or Intolerance to Tumor Necrosis Factor Inhibitors. Arthritis Rheumatol. 2017 Feb;69(2):277-290. doi: 10.1002/art.39944.
PMID: 27860410
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid
mesh term: Hydroxychloroquine
mesh term: Sulfasalazine
mesh term: Methotrexate
mesh term: Leflunomide
participant flow: 
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outcome list: 
reported events: 
certain agreements: 
point of contact: 