<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/NCT01715831</url>
  </required_header>
  <id_info>
    <org_study_id>ML28091</org_study_id>
    <nct_id>NCT01715831</nct_id>
  </id_info>
  <brief_title>A Long-term Safety Extension Study of Tocilizumab in Brazilian Participants With Rheumatoid Arthritis (RA) Who Completed the Studies ML21530 and MA21488</brief_title>
  <acronym>RITACT</acronym>
  <official_title>A Multicenter, Open-Label, Single-Arm Extension Study to Describe the Safety of Tocilizumab Treatment In Brazilian Patients With DMARDs Refractory Rheumatoid Arthritis Which Completed Studies ML21530 and MA21488 and Presenting an Indication of Maintaining the Tocilizumab Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This multicenter, open-label, single-arm extension study will evaluate the long-term safety&#xD;
      of tocilizumab (RoActemra/Actemra) in participants with RA. Participants who have completed&#xD;
      the MA21488 (NCT00810199) core study and the ML21530 (NCT00754572) study and who could&#xD;
      benefit from the study drug, according to the opinion of the investigator, will receive 8&#xD;
      milligrams per kilogram (mg/kg) of intravenous (IV) tocilizumab every 4 weeks. The&#xD;
      anticipated time on study treatment is 104 weeks.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 15, 2013</start_date>
  <completion_date type="Actual">June 6, 2016</completion_date>
  <primary_completion_date type="Actual">June 6, 2016</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Serious Adverse Events (SAEs) and Non-Serious Adverse Events (NSAEs)</measure>
    <time_frame>From Baseline up to approximately 2 years</time_frame>
    <description>An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; significant medical event, according to the investigator discretion (e.g., may represent a risk to the participant or may require medical/surgical intervention to prevent one of the outcomes mentioned above).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With AEs Leading to Dose Modification or Study Discontinuation</measure>
    <time_frame>From Baseline up to approximately 2 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With AEs of Special Interest</measure>
    <time_frame>From Baseline up to approximately 2 years</time_frame>
    <description>Adverse events of special interest included following events: Infections (including opportunistic infections); myocardial infarction / acute coronary syndrome; gastrointestinal (GI) perforations and related events; malignancies; anaphylaxis/hypersensitivity reactions; demyelinating disorders; stroke; hemorrhagic events; and hepatic events. Overall number of participants who experienced any of these AEs of special interest was reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR)</measure>
    <time_frame>Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and follow-up (FU) Visit 1 (Week 108), FU Visit 2 (Week 116)</time_frame>
    <description>DAS28 score is a measure of participant's disease activity calculated using tender joint count in 28 joints (TJC28), swollen joint count in 28 joints (SJC28), participant's global assessment of disease activity (general health [GH]) using visual analog scale (VAS), 0 millimeter (mm)=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS, and acute phase response (erythrocyte sedimentation rate [ESR] in millimeters per hour [mm/hr]) for a total possible score of 0 to 10. The score is calculated using the following formula: DAS28 = [0.56 multiplied by (*) square root (√) of TJC28] plus (+) [0.28*√SJC28]+[0.70*the natural logarithm (ln) ESR]+[0.014*GH]. DAS28-ESR score varies from 0 to 10, where higher scores represent greater disease activity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tender Joint Count (TJC)</measure>
    <time_frame>Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)</time_frame>
    <description>An assessment of 28 joints was conducted for tenderness. Joints were assessed and classified as tender/not tender by pressure and joint manipulation after a physical examination. Artificial joints, arthrodesis or fused joints were not taken into consideration for tenderness.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Swollen Joint Count (SJC)</measure>
    <time_frame>Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)</time_frame>
    <description>An assessment of 28 joints was conducted for swelling. Joints were assessed and classified as swollen/not swollen by pressure and joint manipulation after a physical examination. Artificial joints, arthrodesis or fused joints were not taken into consideration for swelling.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global Evaluation of Disease Activity by the Participant Using VAS Score</measure>
    <time_frame>Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)</time_frame>
    <description>Participant's global assessment of disease activity was measured on a horizontal 0-100 mm VAS, with 0 mm (left end of the line) described as &quot;inactive disease&quot; (free of symptoms and without symptoms of arthritis) and 100 mm (right end of the line) as &quot;disease maximum activity&quot; (maximum activity of arthritis). The participant marked the line according to their assessment and the distance from the left edge was measured.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global Evaluation of Disease Activity by the Physician Using VAS Score</measure>
    <time_frame>Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)</time_frame>
    <description>Physician global assessment of disease activity was measured on a horizontal 0-100 mm VAS, with 0 mm (left end of the line) described as &quot;inactive disease&quot; (free of symptoms and without symptoms of arthritis) and 100 mm (right end of the line) as &quot;disease maximum activity&quot; (maximum activity of arthritis). The physician marked the line according to their assessment and the distance from the left edge was measured.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participant's Pain Assessment Using VAS Score</measure>
    <time_frame>Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)</time_frame>
    <description>Participant's pain assessment was made on a horizontal 0-100 mm VAS, with 0 mm (left end of the line) described as &quot;no pain&quot; and 100 mm (right end of the line) as &quot;unbearable pain&quot;. The participant marked the line according to their assessment and the distance from the left edge was measured.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health Assessment Questionnaire - Disability Index (HAQ-DI) Score</measure>
    <time_frame>Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)</time_frame>
    <description>The Stanford HAQ-DI is a participant-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/personal care, ability to stand-up, eating, walking, hygiene, reaching, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where 0 represents 'no disability' and 3 represents 'very severe, high-dependency disability'.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health Assessment Questionnaire (HAQ) Pain VAS Score</measure>
    <time_frame>Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)</time_frame>
    <description>The HAQ pain VAS is a measure of pain on a continuous 100 mm scale. Participants were asked to indicate how much pain they had in the past week as a result of their illness on a horizontal line from 0 (no pain) to 100 mm (severe pain).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C-Reactive Protein (CRP) Level</measure>
    <time_frame>Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)</time_frame>
    <description>CRP is an acute phase reactant and is a measure of inflammation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ESR Level</measure>
    <time_frame>Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)</time_frame>
    <description>ESR is an acute phase reactant and is a measure of inflammation.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Arthritis, Rheumatoid</condition>
  <arm_group>
    <arm_group_label>Tocilizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 104 weeks. The maximum single dose administered to any participant will be of 800 mg of tocilizumab. Participants may also receive disease-modifying anti-rheumatic drugs (DMARDs) in addition to the tocilizumab treatment in any visit, at the investigator discretion, according to the local prescription information and participant's tolerance.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DMARDs</intervention_name>
    <description>DMARDs may be added to the tocilizumab treatment in any visit, at the discretion of the investigator, according to the local prescription information and participant's tolerance. Study protocol does not specify any particular DMARD.</description>
    <arm_group_label>Tocilizumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tocilizumab</intervention_name>
    <description>Tocilizumab will be administered at 8 mg/kg IV dose every 4 weeks for 104 weeks</description>
    <arm_group_label>Tocilizumab</arm_group_label>
    <other_name>RoActemra; Actemra</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants who have completed their last visit in the core studies ML21530 and&#xD;
             MA21488 and that might benefit from treatment using the study drug according to the&#xD;
             investigator's evaluation&#xD;
&#xD;
          -  Absence of an AE or current or recent laboratory finding that would prevent the use of&#xD;
             the 8 mg/kg dose of the tocilizumab&#xD;
&#xD;
          -  Receiving outpatient treatment&#xD;
&#xD;
          -  For women who are not postmenopausal and are not surgically sterile: agreement to use&#xD;
             at least one adequate method of contraception&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants who have prematurely discontinued the core studies ML21530 and MA21488&#xD;
             for any reason&#xD;
&#xD;
          -  MA21488 study participants who remained untreated with tocilizumab after it's&#xD;
             discontinuation according to the treatment-free remission criteria of MA21488 study&#xD;
&#xD;
          -  Immunization with a live/attenuated vaccine since the last administration of the study&#xD;
             drug in the core studies ML21530 and ML21488&#xD;
&#xD;
          -  Diagnosis after the last visit of the study ML21530 or after the last visit of the&#xD;
             study MA21488 of a rheumatic autoimmune disease other than RA, including systemic&#xD;
             erythematous lupus (SEL), mixed connective tissue disease (MCTD), scleroderma and&#xD;
             polymyositis, or a significant systemic involvement secondary to RA (e.g., vasculitis,&#xD;
             pulmonary fibrosis or Felty's syndrome). Secondary Sjogren's Syndrome and/or nodulosis&#xD;
             with RA are allowed&#xD;
&#xD;
          -  Diagnosis after the last visit of the core study ML21530 or of the study MA21488 of an&#xD;
             inflammatory joint disease other than RA&#xD;
&#xD;
          -  Abnormal laboratory parameters at the baseline&#xD;
&#xD;
          -  History of severe allergic or anaphylactic reactions to humanized or murine monoclonal&#xD;
             antibodies&#xD;
&#xD;
          -  Evidences of a concomitant, serious and uncontrolled illness&#xD;
&#xD;
          -  Known active condition or a history of recurrent infections by bacteria, viruses,&#xD;
             fungi, mycobacteria or other agents&#xD;
&#xD;
          -  Evidence of an active malignant disease, malignancies diagnosed in the last 10 years&#xD;
             or breast cancer diagnosed in the last 20 years&#xD;
&#xD;
          -  Uncontrolled disease status, such as asthma or inflammatory bowel disease in which&#xD;
             acute crises are usually treated with oral or parenteral corticosteroids&#xD;
&#xD;
          -  Current hepatic disease, as determined by the investigator&#xD;
&#xD;
          -  Active tuberculosis (TB) requiring treatment in the previous three years. Participants&#xD;
             should be screened for latent TB according to local practice guidelines and should not&#xD;
             be admitted into the study if latent TB is detected. Participants must not present any&#xD;
             evidence of active TB infection at the enrollment. Participants treated for&#xD;
             tuberculosis without recurrence in three years are allowed&#xD;
&#xD;
          -  History of alcohol, drugs or chemical abuse since the inclusion in the core studies&#xD;
             ML21530 and MA21488&#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 Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Santa Casa de Misericordia de Salvador; Reumatologia</name>
      <address>
        <city>Salvador</city>
        <state>BA</state>
        <zip>40050-410</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Cassiano Antonio Moraes - UFES; Reumatologia</name>
      <address>
        <city>Vitoria</city>
        <state>ES</state>
        <zip>29043-910</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Mineiro de Pesquisa - CMIP</name>
      <address>
        <city>Juiz de Fora</city>
        <state>MG</state>
        <zip>36036-330</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital das Clinicas - UNICAMP</name>
      <address>
        <city>Campinas</city>
        <state>SP</state>
        <zip>13083-888</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Base de Sao Jose do Rio Preto</name>
      <address>
        <city>Sao Jose do Rio Preto</city>
        <state>SP</state>
        <zip>15090-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universidade Federal de Sao Paulo - UNIFESP; Reumatologia</name>
      <address>
        <city>Sao Paulo</city>
        <state>SP</state>
        <zip>04026-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Abreu Sodre - AACD;Reumatologia</name>
      <address>
        <city>Sao Paulo</city>
        <state>SP</state>
        <zip>04027-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Estadual do Servidor Publico; Reumatologia</name>
      <address>
        <city>Sao Paulo</city>
        <state>SP</state>
        <zip>04039-004</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Paulista de Investigacao Clinica - CEPIC</name>
      <address>
        <city>Sao Paulo</city>
        <state>SP</state>
        <zip>04266-010</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>October 25, 2012</study_first_submitted>
  <study_first_submitted_qc>October 25, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 29, 2012</study_first_posted>
  <results_first_submitted>May 19, 2017</results_first_submitted>
  <results_first_submitted_qc>May 19, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">June 12, 2017</results_first_posted>
  <last_update_submitted>May 19, 2017</last_update_submitted>
  <last_update_submitted_qc>May 19, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">June 12, 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>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Tocilizumab</title>
          <description>Participants received tocilizumab 8 milligrams per kilogram (mg/kg) intravenous (IV) infusion every 4 weeks for a total of 104 weeks. The maximum single dose administered to any participant was 800 mg of tocilizumab. Participants might have also received disease-modifying anti-rheumatic drugs (DMARDs) in addition to the tocilizumab treatment in any visit, at the investigator discretion, according to the local prescription information and participant's tolerance.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Intention to treat (ITT) population included all participants who received at least one dose of tocilizumab during the study.</population>
      <group_list>
        <group group_id="B1">
          <title>Tocilizumab</title>
          <description>Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 104 weeks. The maximum single dose administered to any participant was 800 mg of tocilizumab. Participants might have also received DMARDs in addition to the tocilizumab treatment in any visit, at the investigator discretion, according to the local prescription information and participant's tolerance.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="26"/>
          </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="56.0" spread="12.6"/>
                  </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="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Serious Adverse Events (SAEs) and Non-Serious Adverse Events (NSAEs)</title>
        <description>An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; significant medical event, according to the investigator discretion (e.g., may represent a risk to the participant or may require medical/surgical intervention to prevent one of the outcomes mentioned above).</description>
        <time_frame>From Baseline up to approximately 2 years</time_frame>
        <population>ITT population</population>
        <group_list>
          <group group_id="O1">
            <title>Tocilizumab</title>
            <description>Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 104 weeks. The maximum single dose administered to any participant was 800 mg of tocilizumab. Participants might have also received DMARDs in addition to the tocilizumab treatment in any visit, at the investigator discretion, according to the local prescription information and participant's tolerance.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Serious Adverse Events (SAEs) and Non-Serious Adverse Events (NSAEs)</title>
          <description>An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; significant medical event, according to the investigator discretion (e.g., may represent a risk to the participant or may require medical/surgical intervention to prevent one of the outcomes mentioned above).</description>
          <population>ITT population</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>NSAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With AEs Leading to Dose Modification or Study Discontinuation</title>
        <time_frame>From Baseline up to approximately 2 years</time_frame>
        <population>ITT population</population>
        <group_list>
          <group group_id="O1">
            <title>Tocilizumab</title>
            <description>Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 104 weeks. The maximum single dose administered to any participant was 800 mg of tocilizumab. Participants might have also received DMARDs in addition to the tocilizumab treatment in any visit, at the investigator discretion, according to the local prescription information and participant's tolerance.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With AEs Leading to Dose Modification or Study Discontinuation</title>
          <population>ITT population</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AEs leading to dose modification</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AEs leading to study discontinuation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With AEs of Special Interest</title>
        <description>Adverse events of special interest included following events: Infections (including opportunistic infections); myocardial infarction / acute coronary syndrome; gastrointestinal (GI) perforations and related events; malignancies; anaphylaxis/hypersensitivity reactions; demyelinating disorders; stroke; hemorrhagic events; and hepatic events. Overall number of participants who experienced any of these AEs of special interest was reported.</description>
        <time_frame>From Baseline up to approximately 2 years</time_frame>
        <population>ITT population</population>
        <group_list>
          <group group_id="O1">
            <title>Tocilizumab</title>
            <description>Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 104 weeks. The maximum single dose administered to any participant was 800 mg of tocilizumab. Participants might have also received DMARDs in addition to the tocilizumab treatment in any visit, at the investigator discretion, according to the local prescription information and participant's tolerance.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With AEs of Special Interest</title>
          <description>Adverse events of special interest included following events: Infections (including opportunistic infections); myocardial infarction / acute coronary syndrome; gastrointestinal (GI) perforations and related events; malignancies; anaphylaxis/hypersensitivity reactions; demyelinating disorders; stroke; hemorrhagic events; and hepatic events. Overall number of participants who experienced any of these AEs of special interest was reported.</description>
          <population>ITT population</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR)</title>
        <description>DAS28 score is a measure of participant's disease activity calculated using tender joint count in 28 joints (TJC28), swollen joint count in 28 joints (SJC28), participant's global assessment of disease activity (general health [GH]) using visual analog scale (VAS), 0 millimeter (mm)=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS, and acute phase response (erythrocyte sedimentation rate [ESR] in millimeters per hour [mm/hr]) for a total possible score of 0 to 10. The score is calculated using the following formula: DAS28 = [0.56 multiplied by (*) square root (√) of TJC28] plus (+) [0.28*√SJC28]+[0.70*the natural logarithm (ln) ESR]+[0.014*GH]. DAS28-ESR score varies from 0 to 10, where higher scores represent greater disease activity.</description>
        <time_frame>Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and follow-up (FU) Visit 1 (Week 108), FU Visit 2 (Week 116)</time_frame>
        <population>ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tocilizumab</title>
            <description>Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 104 weeks. The maximum single dose administered to any participant was 800 mg of tocilizumab. Participants might have also received DMARDs in addition to the tocilizumab treatment in any visit, at the investigator discretion, according to the local prescription information and participant's tolerance.</description>
          </group>
        </group_list>
        <measure>
          <title>Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR)</title>
          <description>DAS28 score is a measure of participant's disease activity calculated using tender joint count in 28 joints (TJC28), swollen joint count in 28 joints (SJC28), participant's global assessment of disease activity (general health [GH]) using visual analog scale (VAS), 0 millimeter (mm)=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS, and acute phase response (erythrocyte sedimentation rate [ESR] in millimeters per hour [mm/hr]) for a total possible score of 0 to 10. The score is calculated using the following formula: DAS28 = [0.56 multiplied by (*) square root (√) of TJC28] plus (+) [0.28*√SJC28]+[0.70*the natural logarithm (ln) ESR]+[0.014*GH]. DAS28-ESR score varies from 0 to 10, where higher scores represent greater disease activity.</description>
          <population>ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (n=26)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.76" spread="1.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.23" spread="0.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 24 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.43" spread="1.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 36 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.04" spread="0.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 48 (n=21)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.32" spread="1.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 56 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.82" spread="0.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 68 (n=23)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.21" spread="0.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 80 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.06" spread="0.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 92 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.23" spread="0.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 104 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.92" spread="0.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FU Visit 1 (n=13)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.70" spread="1.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FU Visit 2 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.21" spread="1.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tender Joint Count (TJC)</title>
        <description>An assessment of 28 joints was conducted for tenderness. Joints were assessed and classified as tender/not tender by pressure and joint manipulation after a physical examination. Artificial joints, arthrodesis or fused joints were not taken into consideration for tenderness.</description>
        <time_frame>Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)</time_frame>
        <population>ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tocilizumab</title>
            <description>Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 104 weeks. The maximum single dose administered to any participant was 800 mg of tocilizumab. Participants might have also received DMARDs in addition to the tocilizumab treatment in any visit, at the investigator discretion, according to the local prescription information and participant's tolerance.</description>
          </group>
        </group_list>
        <measure>
          <title>Tender Joint Count (TJC)</title>
          <description>An assessment of 28 joints was conducted for tenderness. Joints were assessed and classified as tender/not tender by pressure and joint manipulation after a physical examination. Artificial joints, arthrodesis or fused joints were not taken into consideration for tenderness.</description>
          <population>ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.</population>
          <units>tender joints</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (n=26)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.8" spread="3.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.8" spread="2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 24 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0" spread="3.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 36 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.9" spread="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 48 (n=21)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.8" spread="3.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 56 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.1" spread="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 68 (n=23)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0" spread="2.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 80 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6" spread="2.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 92 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" spread="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 104 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" spread="1.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FU Visit 1 (n=13)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.8" spread="3.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FU Visit 2 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.8" spread="4.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Swollen Joint Count (SJC)</title>
        <description>An assessment of 28 joints was conducted for swelling. Joints were assessed and classified as swollen/not swollen by pressure and joint manipulation after a physical examination. Artificial joints, arthrodesis or fused joints were not taken into consideration for swelling.</description>
        <time_frame>Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)</time_frame>
        <population>ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tocilizumab</title>
            <description>Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 104 weeks. The maximum single dose administered to any participant was 800 mg of tocilizumab. Participants might have also received DMARDs in addition to the tocilizumab treatment in any visit, at the investigator discretion, according to the local prescription information and participant's tolerance.</description>
          </group>
        </group_list>
        <measure>
          <title>Swollen Joint Count (SJC)</title>
          <description>An assessment of 28 joints was conducted for swelling. Joints were assessed and classified as swollen/not swollen by pressure and joint manipulation after a physical examination. Artificial joints, arthrodesis or fused joints were not taken into consideration for swelling.</description>
          <population>ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.</population>
          <units>swollen joints</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (n=26)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.4" spread="2.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" spread="2.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 24 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6" spread="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 36 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9" spread="1.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 48 (n=21)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.4" spread="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 56 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8" spread="1.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 68 (n=23)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9" spread="1.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 80 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" spread="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 92 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8" spread="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 104 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6" spread="1.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FU Visit 1 (n=13)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2" spread="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FU Visit 2 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" spread="2.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Global Evaluation of Disease Activity by the Participant Using VAS Score</title>
        <description>Participant's global assessment of disease activity was measured on a horizontal 0-100 mm VAS, with 0 mm (left end of the line) described as &quot;inactive disease&quot; (free of symptoms and without symptoms of arthritis) and 100 mm (right end of the line) as &quot;disease maximum activity&quot; (maximum activity of arthritis). The participant marked the line according to their assessment and the distance from the left edge was measured.</description>
        <time_frame>Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)</time_frame>
        <population>ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tocilizumab</title>
            <description>Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 104 weeks. The maximum single dose administered to any participant was 800 mg of tocilizumab. Participants might have also received DMARDs in addition to the tocilizumab treatment in any visit, at the investigator discretion, according to the local prescription information and participant's tolerance.</description>
          </group>
        </group_list>
        <measure>
          <title>Global Evaluation of Disease Activity by the Participant Using VAS Score</title>
          <description>Participant's global assessment of disease activity was measured on a horizontal 0-100 mm VAS, with 0 mm (left end of the line) described as &quot;inactive disease&quot; (free of symptoms and without symptoms of arthritis) and 100 mm (right end of the line) as &quot;disease maximum activity&quot; (maximum activity of arthritis). The participant marked the line according to their assessment and the distance from the left edge was measured.</description>
          <population>ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.</population>
          <units>mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (n=26)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.2" spread="25.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12 (n=26)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.4" spread="26.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 24 (n=26)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38.4" spread="27.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 36 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.8" spread="25.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 48 (n=23)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.8" spread="28.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 56 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.6" spread="22.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 68 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.4" spread="24.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 80 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.1" spread="26.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 92 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.2" spread="25.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 104 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.4" spread="25.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FU Visit 1 (n=15)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37.1" spread="28.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FU Visit 2 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.6" spread="29.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Global Evaluation of Disease Activity by the Physician Using VAS Score</title>
        <description>Physician global assessment of disease activity was measured on a horizontal 0-100 mm VAS, with 0 mm (left end of the line) described as &quot;inactive disease&quot; (free of symptoms and without symptoms of arthritis) and 100 mm (right end of the line) as &quot;disease maximum activity&quot; (maximum activity of arthritis). The physician marked the line according to their assessment and the distance from the left edge was measured.</description>
        <time_frame>Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)</time_frame>
        <population>ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tocilizumab</title>
            <description>Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 104 weeks. The maximum single dose administered to any participant was 800 mg of tocilizumab. Participants might have also received DMARDs in addition to the tocilizumab treatment in any visit, at the investigator discretion, according to the local prescription information and participant's tolerance.</description>
          </group>
        </group_list>
        <measure>
          <title>Global Evaluation of Disease Activity by the Physician Using VAS Score</title>
          <description>Physician global assessment of disease activity was measured on a horizontal 0-100 mm VAS, with 0 mm (left end of the line) described as &quot;inactive disease&quot; (free of symptoms and without symptoms of arthritis) and 100 mm (right end of the line) as &quot;disease maximum activity&quot; (maximum activity of arthritis). The physician marked the line according to their assessment and the distance from the left edge was measured.</description>
          <population>ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.</population>
          <units>mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (n=26)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.6" spread="18.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12 (n=26)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.4" spread="14.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 24 (n=26)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.8" spread="14.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 36 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.1" spread="10.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 48 (n=23)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.1" spread="11.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 56 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.0" spread="13.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 68 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.6" spread="11.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 80 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.3" spread="11.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 92 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.7" spread="11.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 104 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.0" spread="9.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FU Visit 1 (n=15)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.7" spread="11.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FU Visit 2 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.3" spread="18.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Participant's Pain Assessment Using VAS Score</title>
        <description>Participant's pain assessment was made on a horizontal 0-100 mm VAS, with 0 mm (left end of the line) described as &quot;no pain&quot; and 100 mm (right end of the line) as &quot;unbearable pain&quot;. The participant marked the line according to their assessment and the distance from the left edge was measured.</description>
        <time_frame>Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)</time_frame>
        <population>ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tocilizumab</title>
            <description>Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 104 weeks. The maximum single dose administered to any participant was 800 mg of tocilizumab. Participants might have also received DMARDs in addition to the tocilizumab treatment in any visit, at the investigator discretion, according to the local prescription information and participant's tolerance.</description>
          </group>
        </group_list>
        <measure>
          <title>Participant's Pain Assessment Using VAS Score</title>
          <description>Participant's pain assessment was made on a horizontal 0-100 mm VAS, with 0 mm (left end of the line) described as &quot;no pain&quot; and 100 mm (right end of the line) as &quot;unbearable pain&quot;. The participant marked the line according to their assessment and the distance from the left edge was measured.</description>
          <population>ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.</population>
          <units>mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (n=26)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.9" spread="21.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12 (n=26)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.0" spread="25.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 24 (n=26)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.7" spread="25.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 36 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.6" spread="21.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 48 (n=23)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.8" spread="25.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 56 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.4" spread="23.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 68 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.8" spread="23.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 80 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.9" spread="24.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 92 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.5" spread="22.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 104 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.6" spread="22.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FU Visit 1 (n=15)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.9" spread="25.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FU Visit 2 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.6" spread="30.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Health Assessment Questionnaire - Disability Index (HAQ-DI) Score</title>
        <description>The Stanford HAQ-DI is a participant-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/personal care, ability to stand-up, eating, walking, hygiene, reaching, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where 0 represents 'no disability' and 3 represents 'very severe, high-dependency disability'.</description>
        <time_frame>Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)</time_frame>
        <population>ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tocilizumab</title>
            <description>Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 104 weeks. The maximum single dose administered to any participant was 800 mg of tocilizumab. Participants might have also received DMARDs in addition to the tocilizumab treatment in any visit, at the investigator discretion, according to the local prescription information and participant's tolerance.</description>
          </group>
        </group_list>
        <measure>
          <title>Health Assessment Questionnaire - Disability Index (HAQ-DI) Score</title>
          <description>The Stanford HAQ-DI is a participant-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/personal care, ability to stand-up, eating, walking, hygiene, reaching, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where 0 represents 'no disability' and 3 represents 'very severe, high-dependency disability'.</description>
          <population>ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (n=26)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.68" spread="0.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12 (n=26)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.49" spread="0.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 24 (n=26)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.49" spread="0.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 36 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.49" spread="0.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 48 (n=23)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.48" spread="0.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 56 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.53" spread="0.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 68 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.52" spread="0.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 80 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.53" spread="0.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 92 (n=23)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.43" spread="0.44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 104 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.48" spread="0.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FU Visit 1 (n=15)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.56" spread="0.42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FU Visit 2 (n=23)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.63" spread="0.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Health Assessment Questionnaire (HAQ) Pain VAS Score</title>
        <description>The HAQ pain VAS is a measure of pain on a continuous 100 mm scale. Participants were asked to indicate how much pain they had in the past week as a result of their illness on a horizontal line from 0 (no pain) to 100 mm (severe pain).</description>
        <time_frame>Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)</time_frame>
        <population>ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tocilizumab</title>
            <description>Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 104 weeks. The maximum single dose administered to any participant was 800 mg of tocilizumab. Participants might have also received DMARDs in addition to the tocilizumab treatment in any visit, at the investigator discretion, according to the local prescription information and participant's tolerance.</description>
          </group>
        </group_list>
        <measure>
          <title>Health Assessment Questionnaire (HAQ) Pain VAS Score</title>
          <description>The HAQ pain VAS is a measure of pain on a continuous 100 mm scale. Participants were asked to indicate how much pain they had in the past week as a result of their illness on a horizontal line from 0 (no pain) to 100 mm (severe pain).</description>
          <population>ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.</population>
          <units>mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (n=26)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.9" spread="22.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12 (n=26)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.8" spread="24.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 24 (n=26)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37.8" spread="26.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 36 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.1" spread="23.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 48 (n=23)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.7" spread="29.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 56 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.3" spread="24.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 68 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.9" spread="25.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 80 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34.4" spread="27.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 92 (n=23)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38.2" spread="30.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 104 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.0" spread="23.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FU Visit 1 (n=15)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.9" spread="24.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FU Visit 2 (n=22)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.3" spread="32.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>C-Reactive Protein (CRP) Level</title>
        <description>CRP is an acute phase reactant and is a measure of inflammation.</description>
        <time_frame>Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)</time_frame>
        <population>ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tocilizumab</title>
            <description>Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 104 weeks. The maximum single dose administered to any participant was 800 mg of tocilizumab. Participants might have also received DMARDs in addition to the tocilizumab treatment in any visit, at the investigator discretion, according to the local prescription information and participant's tolerance.</description>
          </group>
        </group_list>
        <measure>
          <title>C-Reactive Protein (CRP) Level</title>
          <description>CRP is an acute phase reactant and is a measure of inflammation.</description>
          <population>ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.</population>
          <units>milligrams per deciliter (mg/dL)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.51" spread="0.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12 (n=26)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.13" spread="6.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 24 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.08" spread="1.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 36 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.58" spread="3.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 48 (n=21)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.21" spread="0.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 56 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.41" spread="0.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 68 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.43" spread="0.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 80 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.64" spread="1.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 92 (n=23)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.86" spread="7.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 104 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.12" spread="0.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FU Visit 1 (n=13)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.10" spread="0.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FU Visit 2 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.46" spread="5.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>ESR Level</title>
        <description>ESR is an acute phase reactant and is a measure of inflammation.</description>
        <time_frame>Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)</time_frame>
        <population>ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tocilizumab</title>
            <description>Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 104 weeks. The maximum single dose administered to any participant was 800 mg of tocilizumab. Participants might have also received DMARDs in addition to the tocilizumab treatment in any visit, at the investigator discretion, according to the local prescription information and participant's tolerance.</description>
          </group>
        </group_list>
        <measure>
          <title>ESR Level</title>
          <description>ESR is an acute phase reactant and is a measure of inflammation.</description>
          <population>ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.</population>
          <units>mm/hr</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (n=26)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.8" spread="10.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.9" spread="3.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 24 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.5" spread="7.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 36 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.6" spread="3.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 48 (n=21)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.1" spread="4.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 56 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.9" spread="5.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 68 (n=23)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.7" spread="7.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 80 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.4" spread="9.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 92 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.5" spread="9.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 104 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.5" spread="6.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FU Visit 1 (n=13)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.8" spread="5.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FU Visit 2 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.9" spread="29.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From Baseline up to approximately 2 years</time_frame>
      <desc>ITT population</desc>
      <group_list>
        <group group_id="E1">
          <title>Tocilizumab</title>
          <description>Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 104 weeks. The maximum single dose administered to any participant was 800 mg of tocilizumab. Participants might have also received DMARDs in addition to the tocilizumab treatment in any visit, at the investigator discretion, according to the local prescription information and participant's tolerance.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 19.0</default_vocab>
        <default_assessment>Non-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="4" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Corneal perforation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Total lung capacity decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
              </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="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Lung disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 19.0</default_vocab>
        <default_assessment>Non-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="24" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Labyrinthitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Diarrhoea NOS</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Periodontitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Respiratory tract infection NOS</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Dengue fever</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Injury</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dyslipidaemia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Hypercholesterolemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Osteopenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Osteoporosis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Vitamin D deficiency</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Leukocyturia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Hypertension NOS</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </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>The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Medical Communications</name_or_title>
      <organization>Hoffmann-La Roche</organization>
      <phone>800-821-8590</phone>
      <email>genentech@druginfo.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/NCT01715831
org study id: ML28091
nct id: NCT01715831
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This multicenter, open-label, single-arm extension study will evaluate the long-term safety
      of tocilizumab (RoActemra/Actemra) in participants with RA. Participants who have completed
      the MA21488 (NCT00810199) core study and the ML21530 (NCT00754572) study and who could
      benefit from the study drug, according to the opinion of the investigator, will receive 8
      milligrams per kilogram (mg/kg) of intravenous (IV) tocilizumab every 4 weeks. The
      anticipated time on study treatment is 104 weeks.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Serious Adverse Events (SAEs) and Non-Serious Adverse Events (NSAEs)
time frame: From Baseline up to approximately 2 years
description: An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; significant medical event, according to the investigator discretion (e.g., may represent a risk to the participant or may require medical/surgical intervention to prevent one of the outcomes mentioned above).
measure: Number of Participants With AEs Leading to Dose Modification or Study Discontinuation
time frame: From Baseline up to approximately 2 years
measure: Number of Participants With AEs of Special Interest
time frame: From Baseline up to approximately 2 years
description: Adverse events of special interest included following events: Infections (including opportunistic infections); myocardial infarction / acute coronary syndrome; gastrointestinal (GI) perforations and related events; malignancies; anaphylaxis/hypersensitivity reactions; demyelinating disorders; stroke; hemorrhagic events; and hepatic events. Overall number of participants who experienced any of these AEs of special interest was reported.
measure: Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR)
time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and follow-up (FU) Visit 1 (Week 108), FU Visit 2 (Week 116)
description: DAS28 score is a measure of participant's disease activity calculated using tender joint count in 28 joints (TJC28), swollen joint count in 28 joints (SJC28), participant's global assessment of disease activity (general health [GH]) using visual analog scale (VAS), 0 millimeter (mm)=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS, and acute phase response (erythrocyte sedimentation rate [ESR] in millimeters per hour [mm/hr]) for a total possible score of 0 to 10. The score is calculated using the following formula: DAS28 = [0.56 multiplied by (*) square root (√) of TJC28] plus (+) [0.28*√SJC28]+[0.70*the natural logarithm (ln) ESR]+[0.014*GH]. DAS28-ESR score varies from 0 to 10, where higher scores represent greater disease activity.
measure: Tender Joint Count (TJC)
time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
description: An assessment of 28 joints was conducted for tenderness. Joints were assessed and classified as tender/not tender by pressure and joint manipulation after a physical examination. Artificial joints, arthrodesis or fused joints were not taken into consideration for tenderness.
measure: Swollen Joint Count (SJC)
time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
description: An assessment of 28 joints was conducted for swelling. Joints were assessed and classified as swollen/not swollen by pressure and joint manipulation after a physical examination. Artificial joints, arthrodesis or fused joints were not taken into consideration for swelling.
measure: Global Evaluation of Disease Activity by the Participant Using VAS Score
time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
description: Participant's global assessment of disease activity was measured on a horizontal 0-100 mm VAS, with 0 mm (left end of the line) described as "inactive disease" (free of symptoms and without symptoms of arthritis) and 100 mm (right end of the line) as "disease maximum activity" (maximum activity of arthritis). The participant marked the line according to their assessment and the distance from the left edge was measured.
measure: Global Evaluation of Disease Activity by the Physician Using VAS Score
time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
description: Physician global assessment of disease activity was measured on a horizontal 0-100 mm VAS, with 0 mm (left end of the line) described as "inactive disease" (free of symptoms and without symptoms of arthritis) and 100 mm (right end of the line) as "disease maximum activity" (maximum activity of arthritis). The physician marked the line according to their assessment and the distance from the left edge was measured.
measure: Participant's Pain Assessment Using VAS Score
time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
description: Participant's pain assessment was made on a horizontal 0-100 mm VAS, with 0 mm (left end of the line) described as "no pain" and 100 mm (right end of the line) as "unbearable pain". The participant marked the line according to their assessment and the distance from the left edge was measured.
measure: Health Assessment Questionnaire - Disability Index (HAQ-DI) Score
time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
description: The Stanford HAQ-DI is a participant-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/personal care, ability to stand-up, eating, walking, hygiene, reaching, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where 0 represents 'no disability' and 3 represents 'very severe, high-dependency disability'.
measure: Health Assessment Questionnaire (HAQ) Pain VAS Score
time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
description: The HAQ pain VAS is a measure of pain on a continuous 100 mm scale. Participants were asked to indicate how much pain they had in the past week as a result of their illness on a horizontal line from 0 (no pain) to 100 mm (severe pain).
measure: C-Reactive Protein (CRP) Level
time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
description: CRP is an acute phase reactant and is a measure of inflammation.
measure: ESR Level
time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
description: ESR is an acute phase reactant and is a measure of inflammation.
arm group label: Tocilizumab
arm group type: Experimental
description: Participants will receive tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 104 weeks. The maximum single dose administered to any participant will be of 800 mg of tocilizumab. Participants may also receive disease-modifying anti-rheumatic drugs (DMARDs) in addition to the tocilizumab treatment in any visit, at the investigator discretion, according to the local prescription information and participant's tolerance.
intervention type: Drug
intervention name: DMARDs
description: DMARDs may be added to the tocilizumab treatment in any visit, at the discretion of the investigator, according to the local prescription information and participant's tolerance. Study protocol does not specify any particular DMARD.
arm group label: Tocilizumab
intervention type: Drug
intervention name: Tocilizumab
description: Tocilizumab will be administered at 8 mg/kg IV dose every 4 weeks for 104 weeks
arm group label: Tocilizumab
other name: RoActemra; Actemra
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
facility: 
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country: Brazil
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 