Introduction: In CARE-MS II (NCT00548405), alemtuzumab (12mg/day; baseline: 5 days; 12 months later: 3 days) significantly improved clinical/MRI outcomes vs SC IFNB-1a over 2 years (y) in RRMS patients with inadequate response to prior therapy. Efficacy was maintained in a 4-y extension study (NCT00930553), wherein patients could receive additional 3-day alemtuzumab courses (⩾12 months apart) as needed for disease activity or receive other disease-modifying therapy (DMT) per investigator discretion. Further follow-up was available in an additional 5-y extension, TOPAZ (NCT02255656).

Aims: To evaluate the efficacy and safety of alemtuzumab in CARE-MS II patients over 9y.

Methods: At investigator discretion, patients in TOPAZ can receive additional as-needed alemtuzumab (⩾12 months apart; no criteria) or receive other DMT (at any time).

Results: From core study baseline through Y9, 288/435 (66%) CARE-MS II alemtuzumab-treated patients remained on study; 41% received neither additional alemtuzumab nor another DMT through Y9. At Y9, annualised relapse rate was 0.13. From core study baseline through Y9, 68% of patients had stable/improved EDSS scores, and mean change in EDSS was +0.32. Over 9y, 60% of patients were free of 6-month confirmed disability worsening, and 49% achieved 6-month confirmed disability improvement. In Y9, 72% of patients were free of MRI disease activity, 88% were free of new gadolinium-enhancing lesions, and 73% were free of new/enlarging T2 hyperintense lesions. From core study baseline through Y9, median percent cumulative brain volume loss (BVL) was -1.22%; median annual BVL was ⩽0.19% each year over Y3-9. Alemtuzumab had a consistent safety profile over 9y, with the incidence of overall adverse events (AEs) and infections declining through Y9; of patients who received ⩾1 dose of alemtuzumab, cumulative thyroid AE incidence was 44% and immune thrombocytopenia (ITP) incidence was 4%. In Y9, 1 case of ITP (14 months after the 4th course of alemtuzumab) and no new cases of nephropathy were reported. Efficacy and safety in SC IFNB-1a-treated patients from the core study who switched to alemtuzumab in the extension were consistent with those treated with alemtuzumab both in the core and extension.

Conclusions: Efficacy of alemtuzumab on clinical, MRI, and BVL outcomes was maintained over 9y in CARE-MS II patients, with 66% remaining on study and 41% receiving no further treatment through Y9. Safety remained consistent and manageable over 9y.