RESUMO
BACKGROUND: TNF-alpha inhibitors have been shown to reduce the risk of joint damage and improve physical function and quality of life in people with rheumatoid arthritis (RA). This is the first Cochrane review of certolizumab pegol, a new TNF-alpha inhibitor. OBJECTIVES: To assess the effectiveness and safety of certolizumab pegol (CDP870) in patients with RA who have not responded well to conventional disease modifying anti-rheumatic drugs (DMARDs). SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 3), MEDLINE (1966 to November 2009), EMBASE (1966 to November 2009), Scopus (January 2004 to November 2009), TOXLINE (until November 2009), Web of Knowledge (until November 2009); websites of the US Food and Drug Administration (FDA) and European Medicines Evaluation Agency (EMEA) (until November 2009), and reference lists of articles. SELECTION CRITERIA: Randomised controlled trials that compared certolizumab pegol with any other agent including placebo or methotrexate (MTX) in adult RA patients with active rheumatoid arthritis despite current or prior treatment with conventional DMARDs, such as methotrexate (MTX). DATA COLLECTION AND ANALYSIS: Two authors independently assessed search results, trial quality and extracted data. MAIN RESULTS: Five trials were included. We included in the analysis 2394 people for effectiveness and 2094 people for safety. The duration of follow-up was from 12 to 52 weeks, and the range of doses of certolizumab pegol were from 50 to 400 mg subcutaneously (sc). In three trials the control was placebo plus methotrexate (MTX) and in two trials it was just placebo. Significant improvements were observed at 24 weeks with the approved dose of 200 mg certolizumab pegol: American College of Rheumatology (ACR) 50% improvement: risk ratio (RR) 6.01 (95% CI 3.84 to 9.40) with an absolute benefit of 29% (95% CI 25% to 34%), number needed to treat to benefit (NNTB) of 4 (3 to 5) and the Health Assessment Questionnaire (HAQ) mean difference (MD) - 0.39 (95% CI -0.45 to -0.32) (scale 0 to 3). At 52 weeks the results were quite similar: ACR 50% improvement RR 5.27 (95% CI 3.19 to 8.71), HAQ mean difference (MD) - 0.42 (95% CI -0.52 to -0.32). Serious adverse events were more frequent for certolizumab pegol 200 mg, Peto OR 2.02 (95% CI 1.24 to 3.30). The most common adverse events with certolizumab pegol 200 mg were: upper respiratory tract infections, Peto OR 2.21 (95% CI 1.15 to 4.25); hypertension, Peto OR 2.81 (95% CI 1.38 to 5.75); and nasopharyngitis, Peto OR 2.71 (95% CI 1.30 to 5.66). AUTHORS' CONCLUSIONS: With an overall high grade of evidence this review revealed an improvement of clinical results (ACR50, 28 joint disease activity score (DAS-28) remission and HAQ scores) with certolizumab pegol. Adverse events were more frequent with certolizumab; there was a statistically significant increase in the number of serious adverse events, infections and hypertension.
