Background and aims: In the 2-year (y) CARE-MS I trial (NCT00530348), alemtuzumab improved efficacy outcomes versus SC IFNB-1a in treatment-naiive RRMS patients. SC IFNB-1a-treated patients enrolling in 4-y extension (NCT00930553) switched to alemtuzumab (12 mg/day; baseline: 5 days; 12 months later: 3 days), and could receive as-needed additional alemtuzumab (12 mg/day; 3 days; ≥12 months apart) for disease activity or other disease-modifying therapy (DMT). Follow-up continues in TOPAZ (NCT02255656). We present 6-y alemtuzumab efficacy and safety in CARE-MS I SC IFNB-1a-treated patients. Methods: At investigator’s discretion, TOPAZ patients can receive as-needed additional alemtuzumab (≥12 months apart) or other DMTs (any time). Results: 117/139 (84%) extension patients completed TOPAZ Y2 (Y6 post-alemtuzumab); 67% received neither additional alemtuzumab nor another DMT through Y6. Annualised relapse rate at Y6 post-alemtuzumab was 0.19; 85%–92% were relapse-free annually with alemtuzumab. At Y6 postalemtuzumab versus core study baseline, 70% had stable/ improved EDSS scores, and mean EDSS score change was +0.26. Over 6 y, 69% were 6-month confirmed disability worsening-free and 28% had 6-month confirmed disability improvement; 62% were MRI disease activity-free in Y6. Median percent cumulative brain volume loss (BVL) from CARE-MS I baseline was –1.99% through study Y8 (Y0–2, SC IFNB-1a: –1.49%; Y1–6 post-alemtuzumab: –0.50%). Median yearly BVL was ≤–0.15% annually with alemtuzumab. Safety was consistent with CARE-MS I alemtuzumab-treated patients and will be discussed further. Conclusion: Alemtuzumab improved efficacy outcomes, with a consistent safety profile, in CARE-MS I SC IFNB1a-treated patients. Improvements were maintained through Y6, with 67% receiving no additional treatment. Disclosure: STUDY SUPPORT: Sanofi and Bayer HealthCare Pharmaceuticals.