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

Abstract

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

Abbreviations

ABA:

Abatacept

ACR:

American College of Rheumatology

ADA:

Adalimumab

CE:

Cost-effectiveness

CEA:

Cost-effectiveness analysis

CRP:

C-reactive protein

CZP:

Certolizumab pegol

DMARDs:

Disease-modifying antirheumatic drugs

ESR:

Erythrocyte sedimentation rate

ETA:

Etanercept

EULAR:

European League Against Rheumatism

GOL:

Golimumab

GSK:

GlaxoSmithKline

HR:

Hazard ratio

HRQoL:

Health-related quality of life

ICER:

Incremental cost-effectiveness ratio

INF:

Infliximab

MTX:

Methotrexate

OR:

Odds Ratio

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

PRO:

Patient relevant/reported outcomes

QALY:

Quality-adjusted life year

QoL:

Quality of life

RA:

Rheumatoid arthritis

RCT:

Randomized controlled trial

RF:

Rheumatoid factor

RIT:

Rituximab

RR:

Relative risk

SE:

Standard error

SMD:

Standard mean difference

TNF-α:

Tumor necrosis factor-α

TCZ:

Tocilizumab

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Acknowledgments

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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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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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). https://doi.org/10.1007/s10067-016-3435-2

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  • DOI: https://doi.org/10.1007/s10067-016-3435-2

Keywords

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