Comparative effectiveness of biologics for the management of rheumatoid arthritis: systematic review and network meta-analysis
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Our aim was to establish the comparative effectiveness of rheumatoid arthritis (RA) biologics, using a systematic review and network meta-analysis. The systematic review used randomized controlled trials (RCTs) in adults with RA who failed treatment with conventional disease-modifying agents for rheumatoid disease (cDMARDs). We compared the effectiveness of abatacept, adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, and rituximab to tocilizumab, a recent biologic with a different mechanism of action (anti-IL-6 receptor). A network meta-analysis (NMA) included the indirect and direct evidence previously selected. In total, 207 articles were included describing 68 RCTs. The NMA showed that tocilizumab monotherapy was superior to standard care (ACR20, OR 13.27, 95 % CrI [3.958, 43.98]; ACR50, 17.45 [10.18, 31.24]; ACR70, 37.77 [7.226, 216.3]; EULAR, 10.42 [1.963, 54.8]); and methotrexate (MTX; ACR50, OR 5.44 [4.142, 7.238]; ACR70, 7.364 [1.4, 30.83]; EULAR, 4.226 [1.184, 15.58]) at 26 weeks. Similarly, the combination of tocilizumab + MTX was significantly better than standard care/placebo and MTX alone for ACR20, ACR50, ACR70, and EULAR at 26 weeks (OR 18.63 [5.32, 66.81]; 24.27 [14.5, 41.91]; 46.13 [10.08, 277]; 14.23 [2.493, 84.02]; 4.169 [2.267, 7.871]; 5.44 [4.142, 7.238]; 8.731 [4.203, 19.29]; 7.306 [4.393, 13.04], respectively). At 52 weeks, compared to MTX alone, tocilizumab + MTX was significantly better for ACR20 and ACR50 response. Few significant differences were found between tocilizumab (alone or in combination) and any other biologics. Results must be considered in context with the limitations of the available evidence. This NMA suggests that tocilizumab was superior to cDMARDs and as effective as other biologics for RA.
KeywordsAnti-IL-6 receptor Biologics Disease-modifying agents for rheumatoid disease Rheumatoid arthritis Tocilizumab
American College of Rheumatology
Disease-modifying antirheumatic drugs
Erythrocyte sedimentation rate
European League Against Rheumatism
Health-related quality of life
Incremental cost-effectiveness ratio
Preferred Reporting Items for Systematic Reviews and Meta-Analyses
Patient relevant/reported outcomes
Quality-adjusted life year
Quality of life
Randomized controlled trial
Standard mean difference
Tumor necrosis factor-α
This study/analysis was funded by GlaxoSmithKline. The authors would like to acknowledge Jessica Panish for her support and contribution to this manuscript. Copy-edit assistance was provided by Alanna Franchetti of MedErgy and was funded by GSK.
Compliance with ethical standards
Conflicts of interest
• R Alfonso, R Arjunji, and R Ganguly are employees of and own stocks in GSK.
• N Armstrong, R Riemsma, G Worthy, and J Kleijnen are employees of KSR.
• KSR received research funding to conduct the systematic review and the analysis for this research from GSK.
All authors had full control of all primary data and agree to allow the journal to review their data if requested. The manuscript does not report a clinical study or contain patient data.
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