Introduction: Over 2 years (y) in the CARE-MS II phase 3 trials (NCT00548405), 2 courses of alemtuzumab (12 mg/day; baseline: 5 consecutive days; 12 months later: 3 consecutive days) significantly improved clinical and MRI outcomes versus SC IFNB-1a in RRMS patients with inadequate response to prior therapy at baseline. In a 4-y extension (NCT00930553), patients could receive additional courses of alemtuzumab (12 mg/day on 3 consecutive days; ≥12 months apart) as needed for disease activity or receive other disease-modifying therapy (DMT) per investigator discretion; efficacy on clinical/MRI outcomes was maintained in the extension, with 50% receiving no additional alemtuzumab or other DMTs over 6 y after the initial 2 courses. Following the initial 4-y extension, patients could continue in TOPAZ (NCT02255656), an additional 5-y extension study, for further evaluation.

Aims: To evaluate the efficacy and safety of alemtuzumab over 8 y in CARE-MS II patients.

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

Results: Of the 435 patients who received alemtuzumab in CARE-MS II, 300 (69%) completed Y2 of TOPAZ (Y8 after initiating alemtuzumab). 44% received neither additional courses of alemtuzumab nor another DMT through Y8. Annualized relapse rate at Y8 was 0.18; 85% were relapse-free in Y8. 70% of patients had stable/improved EDSS scores from core study baseline through Y8; mean change in EDSS score from core study baseline to Y8 was 0.17. Through Y8, 64% of patients were free from 6-month confirmed disability worsening, and 47% achieved 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 percent cumulative brain volume loss (BVL) from baseline through Y8 was -1.06%; reduction in BVL was 0.19% or less annually in Y3-8. The safety profile in Y8 was consistent with the previous years. The incidence of AEs, infections, and thyroid AEs continued to decline through Y8; no new cases of immune thrombocytopenia or nephropathy were seen.

Conclusion: Efficacy of alemtuzumab on clinical, MRI, and BVL outcomes was maintained over 8 y in the absence of continuous treatment in CARE-MS II patients, with a consistent and manageable safety profile.