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Rheumatology Advance Access originally published online on May 3, 2007
Rheumatology 2007 46(7):1140-1147; doi:10.1093/rheumatology/kem072
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

The efficacy of inhibiting tumour necrosis factor {alpha} and interleukin 1 in patients with rheumatoid arthritis: a meta-analysis and adjusted indirect comparisons

R. Nixon1,2, N. Bansback2,3 and A. Brennan2

1MRC Biostatistics Unit, Cambridge, UK, 2School of Health and Related Research, University of Sheffield, UK and 3Centre for Health Evaluation and Outcome Sciences, St Paul's Hospital, Vancouver, Canada.

Correspondence to: Richard Nixon, MRC Biostatistics Unit, Institute of Public Health, University Forvie Site, Robinson Way, Cambridge CB2 2SR, UK. E-mail: richard.nixon{at}mrc-bsu.cam.ac.uk


  Abstract

Objective. New treatments that inhibit the cytokines tumour necrosis factor {alpha} (TNF{alpha}) and interleukin 1 (IL-1) in the treatment of rheumatoid arthritis have proven clinical effect against placebo and methotrexate (MTX) in several clinical trials in early and late-stage disease and different severity groups. Since there are no head-to-head randomized controlled trials directly comparing the currently available treatments, etanercept, adalimumab, infliximab or anakinra, we perform a meta-analysis that adjusts for differences between study characteristics, and allows indirect comparisons between treatments.

Methods. Thirteen trials of cytokine antagonists were included from a systematic review of the literature. They reported the primary outcome of American College of Rheumatology (ACR) response criteria at 6 months or beyond. Meta-analytical methods are used to quantify relative treatment effects, using the log odds ratio of an ACR20 or ACR50 response at 6 months, whilst adjusting for study-level variables.

Results. In each of the trials, cytokine treatment was efficacious in comparison with placebo or MTX. For each treatment, the inclusion of MTX in combination improved the response. After adjustment for study-level variables, we found TNF{alpha} antagonists to be more efficacious compared with anakinra (P < 0.05). Indirect comparisons between the three TNF{alpha} antagonists indicated no difference in efficacy. Sensitivity analysis using a different statistical model structure confirmed these results.

Conclusion. When the outcome of interest is the probability of an ACR20 or ACR50 response at 6 months we found: (i) treatment with the IL-1 antagonist anakinra is better than placebo; (ii) for each treatment, the use of combination MTX improves the probability of response; (iii) treatment with any of the TNF{alpha} antagonists is better than with the IL-1 antagonist anakinra; and (iv) all drugs in the TNF{alpha} antagonist class are no different from each other.

KEY WORDS: Rheumatoid arthritis, Biologic agents, Meta-analysis

Submitted 8 September 2006; revised version accepted 23 February 2007.
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