***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: This study is a prospect i ve , r and omized , double-blind study to compare the efficacy and safety of 10 mg/kg infliximab with those of 3 mg/kg infliximab treatment in methotrexate-refractory rheumatoid arthritis patients . After the patients received 3 mg/kg infliximab infusion at weeks 0 , 2 , and 6 , they were r and omly assigned to be administered 3 , 6 or 10 mg/kg infliximab every 8 weeks from week 14 to 46 . Mean American College of Rheumatology improvement ( ACR-N ) at week 54 , the primary endpoint , was 51.3 % and 58.3 % for the 3 mg/kg and 10 mg/kg groups , respectively , with a statistically significant difference . Treatment with 10 mg/kg was found to be remarkably beneficial in patients who had not responded to three infusions with 3 mg/kg at week 10 . The median changes in the modified Sharp score were 0.0 in the two groups . There were no significant differences in the incidences of adverse events between the groups . In patients who achieved better clinical response or greater inhibition of progression of joint damage , trough serum infliximab level was significantly higher than in patients who did not . The magnitudes of both efficacies were correlated with the trough serum infliximab level ( Clinical Trials.gov number : NCT00691028 ) Objective To evaluate the efficacy , safety and dose response of a novel oral Janus kinase inhibitor , peficitinib ( ASP015 K ) , as monotherapy in Japanese patients with moderate to severe rheumatoid arthritis ( RA ) . Methods In a 12-week , double-blind study , 281 adult patients with RA with active disease not on concomitant disease-modifying antirheumatic drug therapy were r and omised equally to once-daily placebo or peficitinib 25 , 50 , 100 and 150 mg . The primary endpoint was American College of Rheumatology ( ACR ) 20 response in the peficitinib treatment groups versus placebo at week 12 . Results Mean age was 53.0 years , 81.1 % were female and 25.3 % had previously used antitumour necrosis factor therapy .  Peficitinib 50 , 100 and 150 mg each showed statistically significantly higher ACR20 response rates compared with placebo , and response rates increased up to 150 mg with a statistically significant dose response . The total incidence of treatment-emergent adverse events ( TEAEs ) was similar between the placebo ( 64.3 % ) and peficitinib 25 , 50 , 100 and 150 mg groups ( 70.9 % , 64.9 % , 52.7 % and 67.2 % , respectively ) . TEAEs occurring more frequently in the peficitinib group compared with the placebo group included nasopharyngitis , increased blood creatine phosphokinase and diarrhoea . No cases of serious infections were reported . Herpes zoster occurred in four patients ( two each in peficitinib 25 and 100 mg ) . Conclusions Treatment with peficitinib as monotherapy for 12 weeks in Japanese patients with moderate to severe RA is efficacious and showed acceptable safety profile . These findings support further developments of peficitinib for RA treatment . Trial registration number NCT01649999 ; Results Objective Tofacitinib is an oral Janus kinase ( JAK ) inhibitor for the treatment of rheumatoid arthritis ( RA ) . The pathways affected by tofacitinib and the effects on gene expression in situ are unknown . Therefore , tofacitinib effects on synovial pathobiology were investigated . Methods A r and omised , double-blind , phase II serial synovial biopsy study ( A3921073 ; NCT00976599 ) in patients with RA with an inadequate methotrexate response . Patients on background methotrexate received tofacitinib 10 mg twice daily or placebo for 28 days . Synovial biopsies were performed on Days -7 and 28 and analysed by immunoassay or quantitative PCR . Clinical response was determined by disease activity score and European League Against Rheumatism ( EULAR ) response on Day 28 in A3921073 , and at Month 3 in a long-term extension study ( A3921024 ; NCT00413699 ) . Results Tofacitinib exposure led to EULAR moderate to good responses ( 11/14 patients ) , while placebo was ineffective ( 1/14 patients ) on Day 28 . Tofacitinib treatment significantly reduced synovial mRNA expression of matrix metalloproteinase (MMP)-1 and MMP-3 ( p<0.05 ) and chemokines CCL2 , CXCL10 and CXCL13 ( p<0.05 ) . No overall changes were observed in synovial inflammation score or the presence of T cells , B cells or macrophages . Changes in synovial phosphorylation of signal transducer and activator of transcription 1 ( STAT1 ) and STAT3 strongly correlated with 4-month clinical responses ( p<0.002 ) . Tofacitinib significantly decreased plasma CXCL10 ( p<0.005 ) at Day 28 compared with placebo . Conclusions Tofacitinib reduces metalloproteinase and interferon-regulated gene expression in rheumatoid synovium , and clinical improvement correlates with reductions in STAT1 and STAT3 phosphorylation . JAK1-mediated interferon and interleukin-6 signalling likely play a key role in the synovial response . Trial registration number NCT00976599 Objective To assess the efficacy and safety of low-dose prednisone chronotherapy using a new modified-release ( MR ) formulation for the treatment of rheumatoid arthritis ( RA ) . Methods In this 12-week , double-blind , placebo-controlled study , patients with active RA ( n=350 ) were r and omised 2:1 to receive MR prednisone 5 mg or placebo once daily in the evening in addition to their existing RA disease-modifying antirheumatic drug ( DMARD ) treatment . The primary end point was the percentage of patients achieving a 20 % improvement in RA signs and symptoms according to American College of Rheumatology criteria ( ie , an ACR20 response ) at week 12 . Changes in morning pain , duration of morning stiffness , 28-joint Disease Activity Score and health-related quality of life were also assessed . Results MR prednisone plus DMARD treatment produced higher response rates for ACR20 ( 48 % vs 29 % , p<0.001 ) and ACR50 ( 22 % vs 10 % , p<0.006 ) and a greater median relative reduction from baseline in morning stiffness ( 55 % vs 35 % , p<0.002 ) at week 12 than placebo plus DMARD treatment . Significantly greater reductions in severity of RA ( Disease Activity Score 28 ) ( p<0.001 ) and fatigue ( Functional Assessment of Chronic Illness Therapy-Fatigue score ) ( p=0.003 ) as well as a greater improvement in physical function ( 36-item Short-Form Health Survey score ) ( p<0.001 ) were seen at week 12 for MR prednisone versus placebo . The incidence of adverse events was similar for MR prednisone ( 43 % ) and placebo ( 49 % ) . Conclusion Low-dose MR prednisone added to existing DMARD treatment produced rapid and relevant improvements in RA signs and symptoms . Clinical Trials.gov , number Objectives To compare the efficacy and safety of innovator infliximab ( INX ) and CT-P13 , an INX biosimilar , in active rheumatoid arthritis patients with inadequate response to methotrexate ( MTX ) treatment . Methods Phase III r and omised , double-blind , multicentre , multinational , parallel-group study . Patients with active disease despite MTX ( 12.5–25 mg/week ) were r and omised to receive 3 mg/kg of CT-P13 ( n=302 ) or INX ( n=304 ) with MTX and folic acid . The primary endpoint was the American College of Rheumatology 20 % ( ACR20 ) response at week 30 . Therapeutic equivalence of clinical response according to ACR20 criteria was concluded if the 95 % CI for the treatment difference was within ±15 % . Secondary endpoints included ACR response criteria , European League Against Rheumatism ( EULAR ) response criteria , change in Disease Activity Score 28 ( DAS28 ) , Medical Outcomes Study Short-Form Health Survey ( SF-36 ) , Simplified Disease Activity Index , Clinical Disease Activity Index , as well as pharmacokinetic ( PK ) and pharmacodynamic ( PD ) parameters , safety and immunogenicity . Results At week 30 , ACR20 responses were 60.9 % for CT-P13 and 58.6 % for INX ( 95 % CI −6 % to 10 % ) in the intention-to-treat population . The proportions in CT-P13 and INX groups achieving good or moderate EULAR responses ( C reactive protein ( CRP ) ) at week 30 were 85.8 % and 87.1 % , respectively . Low disease activity or remission according to DAS28–CRP , ACR – EULAR remission rates , ACR50/ACR70 responses and all other PK and PD endpoints were highly similar at week 30 . Incidence of drug-related adverse events ( 35.2 % vs 35.9 % ) and detection of antidrug antibodies ( 48.4 % vs 48.2 % ) were highly similar for CT-P13 and INX , respectively . Conclusions CT-P13 demonstrated equivalent efficacy to INX at week 30 , with a comparable PK profile and immunogenicity . CT-P13 was well tolerated , with a safety profile comparable with that of INX . Clinical Trials.gov Identifier Objectives Rituximab is an effective treatment in patients with established rheumatoid arthritis ( RA ) . The objective of the IMAGE study was to determine the efficacy of rituximab in the prevention of joint damage and its safety in combination with methotrexate ( MTX ) in patients initiating treatment with MTX .  Methods In this double-blind r and omised controlled phase III study , 755 MTX-naïve patients with active RA were r and omly assigned to MTX alone , rituximab 2 × 500 mg + MTX or rituximab 2 × 1000 mg + MTX . The primary end point at week 52 was the change in joint damage measured using a Genant-modified Sharp score . Results 249 , 249 and 250 patients were r and omly assigned to MTX alone , rituximab 2 × 500 mg + MTX or rituximab 2 × 1000 mg + MTX , respectively . At week 52 , treatment with rituximab 2 × 1000 mg + MTX compared with MTX alone was associated with a reduction in progression of joint damage ( mean change in total modified Sharp score 0.359 vs 1.079 ; p=0.0004 ) and an improvement in clinical outcomes ( ACR50 65 % vs 42 % ; p<0.0001 ) ; rituximab 2 × 500 mg + MTX  improved clinical outcomes ( ACR50 59 % vs 42 % ; p<0.0001 ) compared with MTX alone but did not significantly reduce the progression of joint damage . Safety outcomes were similar between treatment groups . Conclusions Treatment with rituximab 2 × 1000 mg in combination with MTX is an effective therapy for the treatment of patients with MTX-naïve RA . CLinical Trials.gov identifier NCT00299104 Objectives The efficacy of tocilizumab ( TCZ ) , an anti-interleukin-6 receptor antibody , has not previously been evaluated in a population consisting exclusively of patients with early rheumatoid arthritis ( RA ) . Methods In a double-blind r and omised controlled trial ( FUNCTION ) , 1162 methotrexate (MTX)-naive patients with early progressive RA were r and omly assigned ( 1:1:1:1 ) to one of four treatment groups : 4 mg/kg TCZ+MTX , 8 mg/kg TCZ+MTX , 8 mg/kg TCZ+placebo and placebo+MTX ( comparator group ) . The primary outcome was remission according to Disease Activity Score using 28 joints ( DAS28–erythrocyte sedimentation rate ( ESR ) < 2.6 ) at week 24 . Radiographic and physical function outcomes were also evaluated . We report results through week 52 . Results The intent-to-treat population included 1157 patients . Significantly more patients receiving 8 mg/kg TCZ+MTX and 8 mg/kg TCZ+placebo than receiving placebo+MTX  achieved DAS28-ESR remission at week 24 ( 45 % and 39 % vs 15 % ; p<0.0001 ) . The 8 m 
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There was no trend toward improved representation of racial/ethnic minority groups or men over time .