044 Durable clinical efficacy of alemtuzumab in patients with active rrms in the absence of continuous treatment: 7-year follow-up of CARE-MS I patients (Topaz Study)

Introduction In CARE-MS I (NCT00530348), alemtuzumab 12 mg/day (baseline: 5 days; 12 months later: 3 days) improved clinical/MRI outcomes versus SC IFNB-1a over 2 years (y) in treatment-naive relapsing-remitting MS (RRMS) patients. Efficacy was durable in a 4-y extension (NCT00930553; 95% enrolled, 92% completed), wherein patients could receive as-needed alemtuzumab retreatment for relapse/MRI activity or other disease-modifying therapies (DMTs) per investigator’s discretion. Patients completing the extension could enrol in the 5-y TOPAZ study (NCT02255656) for further evaluation. Here we examine efficacy/safety through Y7 in alemtuzumab-treated patients from CARE-MS I. Methods In TOPAZ, patients can receive alemtuzumab retreatment (≥12 months apart) or other DMTs (both per investigator’s discretion). MRI scans are performed annually. Assessments: annualised relapse rate (ARR); stable/improved Expanded Disability Status Scale (EDSS) from core study baseline; 6 month confirmed disability worsening (CDW); 6 month confirmed disability improvement (CDI); no evidence of disease activity (NEDA); adverse events (AEs). Results 299/321 patients (93%) completed TOPAZ Y1 (Y7 after initiating alemtuzumab). ARR remained low (Y7: 0.13); 60% were relapse-free in Y3–7. The percentage of patients with stable/improved EDSS remained high (Y7: 78%). Through Y7, 74% were free from 6 month CDW, 37% achieved 6 month CDI, and the majority achieved NEDA each year (Y7: 61%). 59% 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 (15%) and then declined. Conclusion Alemtuzumab efficacy was maintained for 7 years in treatment-naive patients, despite 59% receiving no additional treatment since the initial 2 courses. 37% of patients also showed disability improvement. The alemtuzumab safety profile remained consistent; overall AE incidence decreased over time. Alemtuzumab may provide a unique treatment approach for RRMS patients, offering durable efficacy in the absence of continuous treatment. Study support Sanofi and Bayer HealthCare Pharmaceuticals.