Disability outcomes for alemtuzumab in RRMS patients who relapsed on prior therapy: CARE‐MS II.

OBJECTIVE/BACKGROUND: Alemtuzumab was significantly more effective than subcutaneous interferon beta-1a (SC IFNB-1a) in reducing relapses in 2 clinical trials with treatment-naı¨ve, relapsing-remitting multiple sclerosis (RRMS) patients (pts). Treatment options are limited for RRMS pts experiencing disease activity during therapy, and few controlled studies have been conducted to determine appropriate management. Alemtuzumab and IFNB-1a were compared on disability outcomes in RRMS pts who relapsed on prior therapy. METHODS:Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis II (CARE-MS II) was a 2-year rater-blinded trial with RRMS pts who had relapsed during prior therapy after at least 6 months of treatment. Alemtuzumab treatment was administered IV 12 mg/day (or 24 mg/day in an exploratory cohort) on 5 days at study start and 3 days 12 months later. IFNB-1a treatment was administered 44mcg SC 3-times weekly throughout the study. Entry criteria included 18-55 years old, MS symptom onset within 10 years, and Expanded Disability Status Scale (EDSS) score $\le 5$. EDSS was assessed at baseline and quarterly. The Multiple Sclerosis Functional Composite (MSFC) was assessed at baseline and every 6 months. EDSS and MSFC were assessed by blinded evaluators. Primary endpoints included relapse rate and time to 6-month sustained accumulation of disability (SAD) based on EDSS increase. Additional disability endpoints included changes in EDSS and MSFC. RESULTS: 840 pts from 180 sites in 23 countries were randomized. Baseline characteristics (mean) were: age 35 years; disease duration 3.9 years; EDSS 2.7; with 1.6 and 2.7 relapses in 1 and 2 years prior to study entry, respectively. The most common prior MS therapies were interferon-beta (78.6 %) or glatiramer acetate (32.5 %); less than 5 % of pts had received other prior MS therapy. Risk of 6-month SAD was reduced by 42 % ($p=0.0084$). Additional disability analyses will be reported. Adverse events included infusion-associated reactions and infections of predominantly mild to moderate severity; 16 % of alemtuzumab pts developed an autoimmune thyroid-related adverse event; 1 % developed immune thrombocytopenia. CONCLUSIONSAlemtuzumab more effectively reduced the accumulation of disability than IFNB-1a in a population of RRMS pts who relapsed on prior therapy. Additional analyses of changes in disability will explore the robustness of these results. The safety profile was consistent with previous studies.