Although anti-TNF therapy is successful at controlling disease activity in patients with rheumatoid arthritis (RA), there are those who have an inadequate or unsustained response. Abatacept, also known as CTLA4g, blocks a co-stimulatory signal required for T cell activation. In the ATTAIN trial (Abatacept Trial in the Treatment of Anti-TNF INadequate RA Responders), Genovese, et al (N Engl J Med 2005;353:1114-23) evaluated the efficacy and safety of abatacept in a group of TNF-refractory RA patients.
A summary of the data from this study was summarized in an abstract presented during the 2004 American College of Rheumatology meeting. Overall, using ACR response criteria, patients receiving abatacept had significantly greater improvements in their disease activity than those receiving placebo.
This publication is important in demonstrating that abatacept is effective even in patients with RA who have persistent disease activity in spite of TNF Antagonist therapy. It is important to note that patients did not receive abatacept concomitantly with TNF Antagonists (a combination that has been associated with more infections, however, patients were allowed to take stable doses of other DMARDS. It is notable that the disease characteristics of the patient population enrolled showed longstanding disease with high numbers of swollen and tender joints (22 and 32 respectively), elevated DAS28 scores (6.5), and high mean levels of disability as measured by HAQ (1.8). The clinical responses measured by ACR20 to abatacept were demonstrated within the first 2 weeks with a plateau beginning within one month. While significantly more patients achieved an ACR 20/50/70 response at 6 months with Abatacept (50.4%/20.3%/10.2%) compared to placebo (19.5%/3.8%/1.5%), these were fewer than previously demonstrated for Abatacept in patients who had failed methotrexate. The patients in the current study represent a somewhat different patient population with more recalcitrant disease.
The results of this study suggest that abatacept will offer an option for some patients in whom TNF therapy is not sufficient. Because of its unique mechanism of action, and based on previous data, abatacept may provide an option as well for patients in whom TNF antagonists are not tolerated or may be contraindicated. While the 6-month safety in this study does not indicate any increase in adverse infectious episodes compared to placebo, longer term data is awaited to better understand the risk profile associated wi