Durable Clinical Outcomes With Alemtuzumab in Patients With Active RRMS in the Absence of Continuous Treatment: 7-Year Follow-up of CARE-MS II Patients (TOPAZ Study)

Abstract

Objective: Evaluate efficacy/safety of alemtuzumab over 7 years (y) in relapsing-remitting MS (RRMS) patients from CARE-MS II.

Background: In CARE-MS II (NCT00548405), alemtuzumab (12mg/day, baseline: 5 days; 12 months later: 3 days) significantly improved clinical/MRI outcomes versus SC IFNB-1a over 2 y in patients with inadequate response to prior therapy. Durable efficacy was observed in a 4-y extension (NCT00930553; 93% enrolled, 86% completed), in which patients could receive alemtuzumab retreatment as-needed for relapse/MRI activity or receive other disease-modifying therapies (DMTs) per investigator’s discretion. Patients completing the extension could enroll in TOPAZ (n=336), a 5-y study (NCT02255656), for further evaluation.

Design/Methods: In TOPAZ, patients can receive alemtuzumab retreatment (≥12 months apart) or other DMTs at any time (both per investigator’s discretion). MRI scans are performed annually. Assessments: annualized relapse rate (ARR); 6-month confirmed disability worsening (CDW); 6-month confirmed disability improvement (CDI); no evidence of disease activity (NEDA); AEs.

Results: 317 patients (94%) completed TOPAZ Y1 (Y7 after initiating alemtuzumab). ARR remained low (Y7: 0.14); 51% were relapse-free in Y3–7. The percentage of patients with stable/improved EDSS scores versus baseline remained high (Y7: 73%). At Y7, 69% were 6-month CDW-free, and 44% achieved 6-month CDI. The majority of patients achieved NEDA each year (Y7: 60%). 47% received no additional treatment (alemtuzumab or other DMT) after the initial 2 courses. Overall AE incidence, infusion-associated reactions, and infections decreased over time. Thyroid AE incidence peaked in Y3 (17%) and then declined.

Conclusions: Alemtuzumab efficacy was maintained for 7 y in CARE-MS II patients, despite 47% receiving no additional treatment since the initial 2 courses. 44% of patients also showed improvement in disability. Alemtuzumab safety profile remained consistent; overall AE incidence decreased over time. Alemtuzumab may provide a unique treatment approach for patients, offering durable efficacy in the absence of continuous treatment.