Costimulatory blockade with abatacept (CTLA4-Ig) in relapsing-remitting multiple sclerosis: Results from the ACCLAIM trial

Background: Abatacept (CTLA4‐Ig) is a T cell costimulationblocking agent approved for rheumatoid arthritis. A phase I study of CTLA4‐Ig previously showed feasibility of this approach in subjects with relapsing‐remitting multiple sclerosis (RRMS). Objectives: ACCLAIM (A Cooperative Clinical Study of Abatacept in Multiple Sclerosis) was a phase II, randomized, double‐ blind, placebo‐controlled, multi‐center trial of safety and efficacy of abatacept in participants with RRMS. Methods: Sixty‐five participants were enrolled in the study at 19 clinical sites, representing approximately half of the original enrollment target. Participants were randomized 2:1 in favor of abatacept, and received monthly intravenous infusions of either abatacept or placebo for 24 weeks in blinded fashion. The primary endpoint was the mean number of new inflammatory gadolinium‐enhanced lesions obtained on MRI scans performed every 4 weeks, averaged over the interval from week 8 to week 24. A cross‐over design was employed whereby subjects were switched to the opposite treatment arm at 28 weeks to determine the duration of treatment effect. Inclusion criteria required a diagnosis of definite RRMS according to the McDonald criteria, and active disease defined as either a documented clinical exacerbation or at least one gadoliniumenhanced lesion on MRI in the year prior to enrollment. Results: Low clinical and MRI disease activity were present in both the abatacept and the placebo groups at baseline and during the study. A greater range of gadolinium‐enhanced MRI lesions was noted in the placebo group at baseline. The data were analyzed using a Wilcoxon rank sum test stratified on the presence or absence of gadolinium‐enhanced lesions in the year prior to enrollment. The 24 week results are reported here. No statistically significant difference was observed in the adjusted mean number of new inflammatory MRI brain lesions averaged from week 8 to week 24 between the abatacept group (mean 0.43, SD 0.94, median 0.2, range 0‐5) and the placebo group (mean 1.66, SD 3.63, median 0.3, range 0‐16), p = 0.87. No statistically significant differences were observed in other MRI parameters of MS disease activity, or in clinical assessment of disease activity. Abatacept was well tolerated in this study population. Conclusions: This phase II study did not demonstrate efficacy of abatacept in reducing inflammatory lesions on MRI, nor clinical measures of disease activity in RRMS.