Abatacept (Orencia®; Bristol-Myers Squibb) did not reduce the number of new gadolinium-enhancing Magnetic Resonance Imaging (MRI) lesions in patients with relapsing-remitting multiple sclerosis compared to a placebo after 24 weeks. Results from the Immune Tolerance Network’s ACCLAIM study, led by Samia Khoury, MD (Brigham and Women’s Hospital) were published today in the Multiple Sclerosis Journal.
Multiple sclerosis is understood to be an autoimmune disease driven by T cells, and abatacept is a CTLA4-Ig fusion protein approved for use in rheumatoid arthritis that interferes with the co-stimulatory signal necessary for T cell activation. Investigators hypothesized blocking T-cell activation could help reduce disease activity in patients with a relapsing form of multiple sclerosis.
The ACCLAIM study enrolled 65 adults with relapsing-remitting multiple sclerosis. The trial originally planned to enroll 123 participants, but was stopped at 65 due to slow enrollment. The study consisted of an initial Core Phase in which participants were randomized 2:1, abatacept to placebo, for 28 weeks. After week 28 participants entered an Extension Phase and were crossed-over to the opposite treatment for another 24 weeks. The primary endpoint compared the average number of new brain gadolinium-enhancing Magnetic Resonance Imaging (MRI) lesions between weeks 8 and 24 for the abatacept and placebo groups. Gadolinium enhancing lesions are inflammatory and are a validated indication of multiple sclerosis disease activity. Secondary endpoints assessed clinical measures including multiple sclerosis relapses and disability progression.
There was no statistically significant difference in the average number of new gadolinium-enhancing lesions between the abatacept group (range: 0-5) and placebo group (range: 0-16), and the trial therefore did not meet its primary endpoint. There also were no significant differences between the two groups for other secondary clinical endpoints. Overall, both groups experienced relatively low numbers of new lesions in both the Core and Extension Phases. Because enrollment was truncated at 65, the study was only powered to detect large differences between the abatacept and placebo arms. It remains possible that a treatment effect might have been detectable in a larger study of subjects with higher disease activity.
Clinical datasets from the ACCLAIM study are publicly available via TrialShare, the ITN’s Clinical Trials Research Portal.