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


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.

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Fig. 1





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




  1. Badley E, DesMeules M (2003) Introduction. In: Badley E, DesMeules M, eds. Arthritis in Canada: an ongoing challenge. Ottawa, Canada: Health Canada. Accessed 13 September 2013.

  2. Symmons D, Turner G, Webb R et al (2002) The prevalence of rheumatoid arthritis in the United Kingdom: new estimates for a new century. Rheumatology (Oxford) 41:793–800

    CAS  Article  Google Scholar 

  3. Helmick CG, Felson DT, Lawrence RC et al (2008) Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum 58:15–25

    Article  PubMed  Google Scholar 

  4. Wong R, Davis AM, Badley E, Grewal R, Mohammed M (2010) Prevalence of arthritis and rheumatic diseases around the world: a growing burden and implications for health care needs. In: Models in Care in Arthritis, Bone & Joint Disease (MOCA) Accessed 13 September 2013.

  5. Alamanos Y, Voulgari PV, Drosos AA (2006) Incidence and prevalence of rheumatoid arthritis, based on the 1987 American College of Rheumatology criteria: a systematic review. Semin Arthritis Rheum 36:182–188

    Article  PubMed  Google Scholar 

  6. Filipovic I, Walker D, Forster F, Curry AS (2011) Quantifying the economic burden of productivity loss in rheumatoid arthritis. Rheumatology (Oxford) 50:1083–1090

    Article  Google Scholar 

  7. Sokka T, Kautiainen H, Pincus T et al (2010) Work disability remains a major problem in rheumatoid arthritis in the 2000s: data from 32 countries in the QUEST-RA study. Arthritis Res Ther 12:R42

    Article  PubMed  PubMed Central  Google Scholar 

  8. Pugner KM, Scott DI, Holmes JW, Hieke K (2000) The costs of rheumatoid arthritis: an international long-term view. Semin Arthritis Rheum 29:305–320

    CAS  Article  PubMed  Google Scholar 

  9. Centers for Disease Control and Prevention (2011) Arthritis-related statistics. Atlanta, GA, USA: CDC. Accessed 13 September 2013.

  10. Birnbaum HG, Pike C, Banerjee R, Waldman T, Cifaldi M (2012) Changes in utilization and costs for patients with rheumatoid arthritis, 1997 to 2006. PharmacoEconomics 30:323–336

    Article  PubMed  Google Scholar 

  11. Kawatkar AA, Jacobsen SJ, Levy GD, Medhekar SS, Venkatasubramaniam KV, Herrinton LJ (2012) Direct medical expenditure associated with rheumatoid arthritis in a nationally representative sample from the medical expenditure panel survey. Arthritis Care and Research 64:1649–1656

    Article  PubMed  Google Scholar 

  12. Kleinman NL, Cifaldi MA, Smeeding JE, Shaw JW, Brook RA (2013) Annual incremental health benefit costs and absenteeism among employees with and without rheumatoid arthritis. Journal of Occupational & Environmental Medicine 55:240–244

    Article  Google Scholar 

  13. Simons WR, Rosenblatt LC, Trivedi DN (2012) The economic consequences of rheumatoid arthritis: analysis of Medical Expenditure Panel Survey 2004, 2005, and 2006 data. Journal of Occupational & Environmental Medicine 54:48–55

    Article  Google Scholar 

  14. Poole CD, Currie CJ, Holden S, Singh A (2012) Impact of disease severity on the total, health-related, financial costs of treatment of people with rheumatoid arthritis in the United Kingdom. Presented at: 17th Annual International Meeting of the International Society for Pharmacoeconomics and Outcomes Research, ISPOR; 2-6 June 2012; Washington, DC, USA. Value Health 15:A36–A37

    Article  Google Scholar 

  15. National Collaborating Centre for Chronic Conditions (2009) Rheumatoid arthritis: national clinical guideline for management and treatment in adults [Internet]. London, UK: Royal College of Physicians. Accessed 13 September 2013.

  16. Singh JA, Saag KG, Bridges SL et al (2016) 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol 68:1–26

    PubMed  Google Scholar 

  17. Donahue KE, Jonas DE, Hansen RA et al (2012) Drug therapy for rheumatoid arthritis in adults: an update. Rockville, MD, USA: Agency for Healthcare Research and Quality. Accessed 13 September 2013.

  18. Centre for Reviews and Dissemination (2009) Systematic reviews: CRD’s guidance for undertaking reviews in health care. York, UK: University of York.!SSL!/WebHelp/SysRev3.htm. Accessed 1 April 2014.

  19. Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD et al (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. Br Med J 343:d5928

    Article  Google Scholar 

  20. Higgins JPT, Green S, eds- (2011) Cochrane handbook for systematic reviews of interventions. Version 5.1.0 [updated March 2011]: The Cochrane Collaboration. Accessed 1 April 2014.

  21. Hoaglin D, Hawkins N, Jansen J, Scott D, Itzler R, Cappelleri J et al (2011) Conducting indirect treatment comparison and network meta-analysis studies: report of the ISPOR task force on indirect treatment comparisons: part 2. Value Health 14:429–437

    Article  PubMed  Google Scholar 

  22. Song F, Altman DG, Glenny A-M, Deeks JJ (2003) Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses. Br Med J 326:472

    Article  Google Scholar 

  23. Tvete IF, Natvig B, Gasemyr J, Meland N, Roine M, Klemp M (2015) Comparing effects of biologic agents in treating patients with rheumatoid arthritis: a multiple treatment comparison regression analysis. PLoS One 10:e0137258

    Article  PubMed  PubMed Central  Google Scholar 

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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.

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Correspondence to Rafael Alfonso-Cristancho.

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• 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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Alfonso-Cristancho, R., Armstrong, N., Arjunji, R. et al. Comparative effectiveness of biologics for the management of rheumatoid arthritis: systematic review and network meta-analysis. Clin Rheumatol 36, 25–34 (2017).

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