Objective: Evaluate efficacy/safety of alemtuzumab over 8 years (y) in CARE-MS II patients.

Background: In CARE-MS II (NCT00548405), alemtuzumab (12 mg/day; baseline: 5 days; 12 months later: 3 days) significantly improved clinical/MRI outcomes versus SC IFNB-1a over 2 y in relapsing-remitting MS (RRMS) patients with inadequate response to prior therapy. Efficacy was maintained in a 4-y extension (NCT00930553), in which patients could receive additional, as-needed alemtuzumab (12 mg/day on 3 days; ≥12 months apart) for disease activity or other disease-modifying therapy (DMT) per investigator discretion. Following the initial 4-y extension, patients could continue in TOPAZ (NCT02255656), an additional 5-y extension.

Design/Methods: Patients in TOPAZ can receive additional alemtuzumab (≥12 months apart) or other DMT (at any time), both per investigator’s discretion.

Results: 300/435 patients (69%) completed Y2 of TOPAZ (Y8 after initiating alemtuzumab). 44% received neither additional alemtuzumab nor another DMT through Y8. At Y8, annualized relapse rate was 0.18; 85% were relapse-free. From core study baseline to Y8, 70% of patients had stable/improved EDSS scores; mean EDSS score change was +0.17. Through Y8, 64% of patients were free of 6-month confirmed disability worsening; 47% attained 6-month confirmed disability improvement. In Y8, 58% of patients achieved no evidence of disease activity, 70% were free of MRI disease activity, 89% were free of new Gd-enhancing lesions, and 70% were free of new/enlarging T2 hyperintense lesions. Median cumulative brain volume loss (BVL) from baseline through Y8 was −1.06%; annual BVL was ≤0.19% in Y3–8. Incidence of overall adverse events (AEs) and infections decreased through Y8. Thyroid AE incidence peaked at 17% in Y3, declining thereafter.

Conclusions: Efficacy of alemtuzumab on clinical, MRI, and BVL outcomes was maintained over 8 y without continuous treatment in CARE-MS II patients, with a consistent and manageable safety profile.