Safety profile of abatacept in rheumatoid arthritis: a review.

Background: Abatacept, a soluble human fusion protein that selectively modulates the costimulatory signal required for full T-cell activation, is approved for the treatment of rheumatoid arthritis (RA) in the United States, Canada, and the European Union. Because rare but serious adverse effects have been associated with biologic therapies, it is important to assess the safety profiles of these agents on an ongoing basis.

Objective: This article reviews current evidence on the safety profile of abatacept in patients with RA.

Methods: PubMed/MEDLINE was searched for clinical trials of abatacept using the terms abatacept OR CTLA4Ig, rheumatoid arthritis, and safety. Searches of abstracts presented at the 2007-2009 annual meetings of the American College of Rheumatology, European League Against Rheumatism, and Canadian Rheumatology Association were also conducted. Reports from clinical trials of at least 6 months' duration that evaluated abatacept in adults with RA were included in the review.

Results: Seven placebo-controlled trials and 1 open- label trial were included in the review, as were the long-term extensions of 5 of the studies and an integrated safety analysis. Abatacept added to methotrexate had an acceptable safety profile in patients with RA who had an inadequate response to methotrexate or other traditional disease-modifying antirheumatic drugs, or who failed to respond to treatment with anti-tumor necrosis factor agents. In the 5 core trials, discontinuations due to adverse events ranged from 1.9% to 8.7% of abatacept recipients and 0.9% to 4.3% of placebo recipients. In the integrated safety analysis, serious infections were reported in 3.0% of abatacept recipients and 1.9% of placebo recipients; the corresponding rates of malignancies were 3.7% and 2.9%. No additional safety concerns emerged during up to 7 years of exposure in the long-term extension studies. Antibodies to abatacept developed in ≤3% of patients, with no association found between immunogenicity and adverse events.

Conclusion: Based on the evidence reviewed, abatacept had an acceptable safety profile and was well tolerated in patients with RA.