Clinical Rheumatology

, Volume 36, Issue 1, pp 25–34 | Cite as

Comparative effectiveness of biologics for the management of rheumatoid arthritis: systematic review and network meta-analysis

  • Rafael Alfonso-CristanchoEmail author
  • Nigel Armstrong
  • Ramesh Arjunji
  • Rob Riemsma
  • Gill Worthy
  • Rita Ganguly
  • Jos Kleijnen
Original Article


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.


Anti-IL-6 receptor Biologics Disease-modifying agents for rheumatoid disease Rheumatoid arthritis Tocilizumab 





American College of Rheumatology






Cost-effectiveness analysis


C-reactive protein


Certolizumab pegol


Disease-modifying antirheumatic drugs


Erythrocyte sedimentation rate




European League Against Rheumatism






Hazard ratio


Health-related quality of life


Incremental cost-effectiveness ratio






Odds Ratio


Preferred Reporting Items for Systematic Reviews and Meta-Analyses


Patient relevant/reported outcomes


Quality-adjusted life year


Quality of life


Rheumatoid arthritis


Randomized controlled trial


Rheumatoid factor




Relative risk


Standard error


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.

Supplementary material

10067_2016_3435_MOESM1_ESM.pdf (700 kb)
ESM 1 (PDF 700 kb)


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Copyright information

© International League of Associations for Rheumatology (ILAR) 2016

Authors and Affiliations

  • Rafael Alfonso-Cristancho
    • 1
    Email author
  • Nigel Armstrong
    • 2
  • Ramesh Arjunji
    • 1
  • Rob Riemsma
    • 2
  • Gill Worthy
    • 2
  • Rita Ganguly
    • 1
  • Jos Kleijnen
    • 2
    • 3
  1. 1.GlaxoSmithKlineCollegevilleUSA
  2. 2.Kleijnen Systematic Reviews LtdYorkUK
  3. 3.School for Public Health and Primary Care (CAPHRI)Maastricht UniversityMaastrichtThe Netherlands

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