Results from the double-blind, randomized, placebo-controlled phase II ACCLAIM study indicate that abatacept has no effect on reducing the number of new gadolinium-enhancing lesions on MRI in patients with relapsing-remitting multiple sclerosis, according to Samia J. Khoury, MD, of Brigham and Women’s Hospital, Boston, and her colleagues from the Immune Tolerance Network.
In the ACCLAIM (A Cooperative Clinical Study of Abatacept in Multiple Sclerosis) study, 42 patients who received abatacept (Orencia) developed a mean of 0.43 new gadolinium-enhancing lesions by week 24, compared with 1.66 for 20 placebo-treated patients (P = .87). None of the secondary MRI endpoints (lesion volume change and percent brain volume change) and clinical endpoints (changes in Multiple Sclerosis Functional Composite score, Expanded Disability Status Scale [EDSS], and annualized relapse rate) at 24 weeks differed significantly between the groups. The rate of patients who met criteria for no evidence of disease activity or its components (no EDSS progression, no clinical exacerbations, and no new gadolinium-enhancing MRI lesion) from week 8 and before week 28 did not differ between the groups.
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During a 28-week extension phase in which the groups switched treatments, patients who switched from abatacept to placebo had a greater number of gadolinium-enhancing lesions than did those who switched from placebo to abatacept (1.25 vs. 0.60, respectively), but the difference was not statistically significant.
Abatacept, which is approved for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis, is a CTLA4 immunoglobulin fusion protein that inhibits the activation of T lymphocytes by targeting the adaptive arm of the immune system by blocking the CD28-B7 costimulatory pathway. It was thought to have potential to reduce immune-mediated disease activity in relapsing-remitting multiple sclerosis because T lymphocytes have been implicated in its pathogenesis.
The investigators closed enrollment for the trial early because of slow accrual. The 65 total patients who enrolled in the trial were about half of the number designated in the trial design (n = 123) in order to demonstrate a treatment effect of 50% reduction of new gadolinium-enhancing MRI lesions.
The number of participants “was too small to demonstrate efficacy at the 50% level,” the investigators wrote, and “low numbers of new gadolinium-enhancing MRI lesions in the study population reduced the chances of demonstrating a treatment effect for abatacept.”
A prior phase II trial of abatacept that was stopped early due to safety events yielded inconclusive results because of an imbalance in the baseline disease activity of participants.
Read the full report online in Multiple Sclerosis Journal (Mult Scler J. 2016 Aug 1. doi: 10.1177/1352458516662727).