Abatacept has been shown to be an effective biologic agent for use in the treatment of rheumatoid arthritis, according to findings of a Cochrane review of seven studies involving almost 3,000 patients.

Of the 2,908 patients included in this review, 1,863 were randomized to abatacept and 1,045 to placebo. Most were white women, and their average age was 48.3-55.8 years, depending on the trial. Most trials used a dose of 10 mg/kg of abatacept, and patients continued to use a disease-modifying antirheumatic drug (DMARD) in addition to abatacept for the duration of the study, according to the review’s authors, Lara Maxwell of the University of Ottawa and Dr. Jasvinder A. Singh of the Minneapolis Veterans Affairs Medical Center.

Patients treated with abatacept were 2.2 times more likely than those on placebo to have an ACR 50 response – that is, a 50% improvement based on American College of Rheumatology criteria, which was the primary end point – at the end of year 1 (relative risk, 2.21). There was a 21% absolute risk difference between the two groups. The number needed to achieve an ACR 50 was five patients.

Physical function significantly improved and both disease activity and pain lessened in patients who were treated with abatacept, compared with placebo.

Findings from one of the seven randomized, controlled trials in the review showed that abatacept significantly slowed radiographic progression of joint damage at 12 months, compared with placebo. However, it is unclear whether that finding had any clinical relevance. The other six studies did not assess radiographic progression.

The rate of adverse events was greater in abatacept-treated patients than in those on placebo (RR, 1.05). The number of infections after 12 months was significantly greater in the abatacept group vs. the placebo group (Peto odds ratio, 1.91). Serious adverse events were increased when abatacept was used in combination with other biologics (RR, 2.3), an observation that led the authors to recommend that abatacept should not be used in combination with other biologics to treat RA.

Of the seven studies included in the review, only two were free of any risk of bias arising from flawed methodology. Four of the seven did not address incomplete efficacy outcome data; two of those four also did not address incomplete safety outcome data; and a fifth study provided unclear information on both adequate sequence generation and allocation concealment. In addition, because all the included trials were funded by abatacept’s manufacturer, it is possible that the findings overestimated the treatment benefit, according to Ms. Maxwell and Dr. Singh.

The studies that were included in this Cochrane review were identified through an extensive literature search. The selected trials were all randomized, controlled studies evaluating the effectiveness and safety of abatacept either alone or in combination with a DMARD or another biologic, vs. placebo alone or a DMARD or biologic, in patients with moderate to severe RA.

The cost of 1 year of abatacept therapy is estimated to be approximately £14,000. The prevalence of RA in the United Kingdom is estimated to be 0.8% among adults. Although abatacept has not been approved for use in the United Kingdom, it is approved for use in Europe.

Abatacept was approved by the U.S. Food and Drug Administration in 2005 for use in adults to treat moderate to severe RA that did not respond adequately to either oral DMARDs (such as methotrexate) or to tumor necrosis factor–alpha antagonists, according to the report (Cochrane Database Syst. Rev. 2009 Oct. 7 [doi:10.1002/14651858.CD007277.pub2]).

Abatacept is the first biologic agent to work by disrupting T-cell activation. The drug is a selective costimulation modulator, inhibiting T-lymphocyte activation by binding to CD80 and CD86, thereby blocking interaction with CD28.

All the trials included in this review were funded by Bristol-Myers Squibb Co., the manufacturer of abatacept.

The authors declared that they received financial support from the University of Ottawa and the Minneapolis VA Medical Center.

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

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