Objective: Evaluate efficacy and safety of alemtuzumab in CARE-MS II patients over 9 years.

Background: In CARE-MS II (NCT00548405), alemtuzumab (12 mg/day; baseline: 5 days; 12 months later: 3 days) significantly improved clinical/MRI outcomes vs subcutaneous interferon beta-1a (SC IFNB-1a) over 2 years in RRMS patients. Efficacy was maintained in a 4-year extension (NCT00930553), wherein patients could receive additional 3-day alemtuzumab (≥12 months apart, as-needed) or other disease-modifying therapy (DMT) per investigator discretion. Further follow-up was available in an additional 5-year extension, TOPAZ (NCT02255656).

Design/Methods: Patients in TOPAZ can receive additional alemtuzumab (≥12 months apart; no criteria) or other DMT.

Results: From core study baseline through Y9, 288/435 (66%) CARE-MS II alemtuzumab-treated patients remained on study and 41% received neither additional alemtuzumab nor another DMT. Annualized relapse rate was 0.19 in Y3–9. From baseline to Y9, 68% of patients had stable/improved EDSS scores, mean change in EDSS was +0.32, 60% were free of 6-month confirmed disability worsening, and 49% achieved 6-month confirmed disability improvement. On average, 69% of patients were free of MRI disease activity, 89% were free of new gadolinium-enhancing lesions, and 69% were free of new/enlarging T2 hyperintense lesions per year from Y3–9. Median percent brain volume loss (BVL) was 1.22% cumulatively and ≤0.19% annually over Y3–9. Incidence of overall adverse events (AEs) and infections declined through Y9; cumulative thyroid AE incidence was 44% and immune thrombocytopenia incidence was 3.7% (1 new case in Y9). Efficacy and safety in core study SC IFNB-1a–treated patients 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 9 years in CARE-MS II patients. Safety in Y9 in this study was consistent with that of previous years.

Disclosure: Dr. Bass has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting fees/fees for non-CME services from commercial interests or their agents (Biogen, EMD Serono, Mallinckrodt, Novartis, Roche-Genentech, Sanofi, and TG Therapeutics).. Dr. Bass has received research support from Grant and research support (Biogen, EMD Serono, Mallinckrodt, Novartis, Roche-Genentech, Sanofi, and TG Therapeutics).. Dr. Alroughani has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bayer, Biogen, Biologix, Merck, Novartis, Roche, and Sanofi. Dr. Alroughani has received research support from Biogen, Merck, Novartis, Roche, and Sanofi.Dr. Broadley has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Honoraria for participation in advisory boards (Bayer Schering, Biogen, Merck Serono, Novartis, and Sanofi); conference travel sponsorship (Bayer Schering, Biogen, Merck Serono, Novartis, and Sanofi); speaker honoraria (Biogen and Genzyme).. Dr. Broadley has received research support from Unencumbered research grant (Biogen).. Dr. Comi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with honoraria for consultancy and/or speaking activities from Almirall, Biogen, Bayer, Chugai, Genzyme, Merck Serono, Novartis, Roche, Receptos, Sanofi, Serono Symposia International Foundation, and Teva.. Dr. Comi has received personal compensation in an editorial capacity for Clinical Investigation; European Journal of Neurology and Multiple Sclerosis; Neurological Sciences. Dr. Mao-Draayer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting fees and/or grant support (Acorda, Bayer, Biogen, Celgene, Chugai, EMD Serono, Genzyme, Novartis, Questcor, and Teva Neuroscience).. Dr. Mao-Draayer has received research support from Consulting fees and/or grant support (Acorda, Bayer, Biogen, Celgene, Chugai, EMD Serono, Genzyme, Novartis, Questcor, and Teva Neuroscience). Grant support (NIH NIAID Autoimmunity Center of Excellence: UM1-AIII0557; NIH NINDO R01-NS080821).. Dr. Hartung has received personal compensation from Bayer Healthcare, Biogen Idec, CSL Behring, GeNeuro, Genzyme, MedImmune, Merck Serono, Novartis, Opexa, Receptos, Roche, Sanofi, Teva, and Viela Bio.Dr. Havrdova has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Biogen, Celgene Corporation, Merck, Novartis, Roche, Sanofi, and Teva. Dr. Havrdova has received research support from Czech Ministry of Education, project PROGRES Q27/LF1.Dr. Kim has received personal compensation from Bayer Schering Pharma, Biogen, Eisai, HanAll BioPharma, MedImmune/Viela Bio, Merck Serono, Novartis, Sanofi Genzyme, Teva-Handok, UCB Dr. Kim has received personal compensation in an editorial capacity for Co-editor/associate editor from Journal of Clinical Neurology; Multiple Sclerosis Journal – Experimental, Translational and Clinical. Dr. Kim has received research support from Sanofi Genzyme, Teva-Handok, UCB.Dr. Nakamura has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Speaking fees (Biogen, Novartis, and Sanofi).. Dr. Nakamura has received royalty, license fees, or contractual rights payments from Royalty fees for licenses (Biogen).. Dr. Nakamura has received research support from Research support (Biogen, Novartis, and Sanofi).. Dr. Navas has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting and speaking fees (Bayer Schering, Genzyme, Merck Serono, Novartis, Roche, and Stendhal).. Dr. Navas has received research support from Research support (Merck Serono, Novartis, and Roche).. Dr. Rovira has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis, Sanofi-Genzyme, Icometrix, Bayer, Biogen, Neurodiem, Sanofi-Genzyme, Merck-Serono. Dr. Rovira has received compensation for serving on the Board of Directors of Icometrix. Biogen, Novartis, Roche, Merck, Genzyme and Celgene RocheDr. Vermersch has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Almirall, Biogen, Celgene, Merck Serono, Novartis, Roche, Sanofi, Servier, and Teva. Dr. Vermersch has received research support from Almirall, Biogen, Celgene, Merck Serono, Novartis, Roche, Sanofi, Servier, and Teva.Dr. Wray has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting, principal investigator, and/or speaking fees (Alkermes, Biogen, Celgene, EMD Serono, Genentech/Roche, Novartis, Sanofi Genzyme, and TG Therapeutics).. Dr. Wray has received research support from Consulting, principal investigator, and/or speaking fees (Alkermes, Biogen, Celgene, EMD Serono, Genentech/Roche, Novartis, Sanofi Genzyme, and TG Therapeutics).. Dr. Choudhry has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi. Dr. Daizadeh has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sanofi. Dr. Afsar has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi.. Dr. Singer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting and/or speaking fees from AbbVie, Acorda, Alexion, Bayer, Biogen, Celgene, EMD Serono, Genentech, Novartis, Roche, Sanofi Genzyme, Teva and TG Therapeutics. Dr. Singer has received research support from Barry Singer has received research grant support from AbbVie, Alkermes, Biogen, MedImmune, Novartis, Roche, and Sanofi Genzyme.