A systematic review of the effectiveness of adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis in adults and an economic evaluation of their cost-effectiveness

Authors: Chen YF, Jobanputra P, Barton P, Jowett S, Bryan S, Clark W, Fry-Smith A, Burls A

Journal: Health Technology Assessment Volume: 10 Issue: 42

Publication date: November 2006

DOI: http://dx.doi.org/10.3310/hta10420


Chen YF, Jobanputra P, Barton P, Jowett S, Bryan S, Clark W, et al.A systematic review of the effectiveness of adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis in adults and an economic evaluation of their cost-effectiveness. Health Technol Assess 2006;10(42)

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This report reviews the clinical effectiveness and cost-effectiveness of adalimumab, etanercept and infliximab, agents that inhibit tumour necrosis factor-alpha (TNF-alpha), when used in the treatment of rheumatoid arthritis (RA) in adults.

Data sources

Electronic databases were searched up to February 2005.

Review methods

Systematic reviews of the literature on effectiveness and cost-effectiveness were undertaken and industry submissions to the National Institute for Health and Clinical Excellence (NICE) were reviewed. Meta-analyses of effectiveness data were also undertaken for each agent. The Birmingham Rheumatoid Arthritis Model (BRAM), a simulation model, was further developed and used to produce an incremental cost-effectiveness analysis.


Twenty-nine randomised controlled trials (RCTs), most of high quality, were included. The only head-to-head comparisons were against methotrexate. For patients with short disease duration (


Adalimumab, etanercept and infliximab are effective treatments compared with placebo for RA patients who are not well controlled by conventional DMARDs, improving control of symptoms, improving physical function, and slowing radiographic changes in joints. The combination of a TNF inhibitor with methotrexate was more effective than methotrexate alone in early RA, although the clinical relevance of this additional benefit is yet to be established, particularly in view of the well-established effectiveness of MTX alone. An increased risk of serious infection cannot be ruled out for the combination of methotrexate with adalimumab or infliximab. The results of the economic evaluation based on BRAM are consistent with the observations from the review of clinical effectiveness, including the ranking of treatments. TNF inhibitors are most cost-effective when used as last active therapy. In this analysis, other things being equal, etanercept may be the TNF inhibitor of choice, although this may also depend on patient preference as to route of administration. The next most cost-effective use of TNF inhibitors is third line, as recommended in the 2002 NICE guidance. Direct comparative RCTs of TNF inhibitors against each other and against other DMARDs, and sequential use in patients who have failed a previous TNF inhibitor, are needed. Longer term studies of the quality of life in patients with RA and the impact of DMARDs on this are needed, as are longer studies that directly assess effects on joint replacement, other morbidity and mortality.

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