Authors' objectives:

This report reviews the evidence of the clinical and cost-effectiveness of anakinra, an interleukin-1 receptor antagonist (IL-1Ra), for the treatment of rheumatoid arthritis (RA) in adults.

Authors' results and conclusions: The results of the clinical trials are consistent with clinical benefit (compared with placebo) as measured by American College of Rheumatology (ACR) composite response rate at 6 months. Variation in response rate was seen across the trials, which is likely to be a reflection of the size of the trials and the wide range of doses evaluated. Consistent benefit was seen at the higher dose evaluated [number needed to treat (NNT) to achieve an ACR20 response of 7, 95% confidence interval (CI) 5 to 11, at licensed dose]. Benefit was evident both with monotherapy and when used in combination with methotrexate. Data on the efficacy end-points evaluated in a large pragmatic safety study (0757) have not been made available. This is of concern. Given the nature and scale of this study such data have the potential to alter the overall findings of this review. In the absence of data the reviewers made an educated guess about the result of trial 0757. Assuming that this trial failed to reach conventional levels of statistical significance with a p-value of treatment difference in the order of p < 0.1 to < 0.2, an estimate of effectiveness was derived for trial 0757. The derived estimate has been combined with the data from the earlier trials, using a random effects model, to give a best estimate about anakinras effectiveness for ACR20 response: relative risk 1.43 (95% CI 1.16 to 1.76), risk difference 0.11 (95% CI 0.04 to 0.18), NNT 9 (95% CI 6 to 25). Anakinra can be considered modestly effective in the treatment of RA based on ACR response. Reduction in Health Assessment Questionnaire scores, a measure of disability, was small. Robust data on radiologically assessed joint damage are not currently available. No conclusion can therefore be made on the effect of treatment on disease progression. Direct comparisons with other biological modifiers are not available. Adjusted indirect comparison suggests that anakinra may be significantly less effective at relieving the clinical signs and symptoms of RA, as measured by the ACR response criteria, than tumour necrosis factor (TNF) inhibitors all used in combination with methotrexate. Such indirect results should be interpreted with caution, but can be useful in guiding clinical practice in the absence of direct comparisons between agents. Anakinra treatment was associated with a high incidence of injection-site reactions. Serious adverse events were infrequent, but longer term follow-up is required.

Authors' recommendations: Recommendations for research: - Current clinical trials with anakinra are of limited duration. RCTs are required to evaluate the efficacy, safety and cost of anakinra over the longer term in patients with such a chronic disease. - Comparative trials of anakinra with other DMARDs and biological modifiers are needed to identify the comparative efficacy of these drugs and to guide clinical practice to optimise patient care. - Trials are required to assess the role of anakinra in the treatment of patients who have failed to achieve a benefit while taking infliximab or etanercept. - Further research is needed to assess the impact of DMARDs and anakinra on joint replacement, mortality and quality of life. Continued pharmacovigilance and analysis of potential adverse effects of new and old DMARDs are essential.- Optimal treatment of RA may require combinations of therapeutic compounds that inhibit different mediators. Controlled clinical trials of combination therapy with two anticytokines are required to inform clinical practice, before such an approach is widely adopted. - Suggestions that newer biological therapies reduce radiographic damage without necessarily improving clinical outcomes need to be confirmed if treatments in the absence of a clinical response are to be justified. - Further research is needed to improve the utility of radiographic outcomes in clinical trials of RA, either by building on existing efforts with plain radiographs or through the use of newer imaging methods.

Authors' methods: Systematic review, Economic evaluation

Project Status: Completed

URL for project: http://www.hta.ac.uk/execsumm/summ818.htm

Year Published: 2004

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: England, United Kingdom

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk

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