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) (P6.369)

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. Study Supported by: Sanofi and Bayer HealthCare Pharmaceuticals. Disclosure: Dr. Singer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Acorda, Bayer, Biogen, EMD Serono, Genentech, Novartis, Sanofi Genzyme, and Teva. Dr. Singer has received research support from Acorda, Alkermes, Biogen, MedImmune, Novartis, Roche, and Sanofi Genzyme. Dr. Alroughani has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bayer, Biogen, Merck, Novartis, Roche, Sanofi-Genzyme. Dr. Alroughani has received research support from Biogen, Novartis, Sanofi-Genzyme. Dr. Brassat has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bayer, Biogen, MedDay, Merck Serono, Novartis, Sanofi-Genzyme, Roche, Teva. Dr. Broadley has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bayer-Schering, Biogen, Merck Serono, Novartis, and Sanofi. Dr. Broadley has received research support from Biogen. Dr. Hartung has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen Idec, GeNeuro, Sanofi Genzyme, Merck, Novartis Pharmaceuticals, Octapharma, Opexa Therapeutics, Teva Pharmaceuticals, MedImmune, Bayer HealthCare, Forward Pharma, and Roche. Dr. Havrdova has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Biogen, Merck Serono, Novartis, Receptos, Roche, Sanofi, and Teva; supported by Ministry of Education of Czech Republic (PROGRES Q27/LF1). Dr. Kim has nothing to disclose. Dr. Oreja-Guevara has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion, Biogen, Merck Serono, Novartis, Roche, Sanofi, and Teva. Dr. Pozzilli has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Biogen, Merck, Novartis, Sanofi, and Teva. Dr. Pozzilli has received research support from Actelion, Biogen, Merck, Novartis, Sanofi, and Teva. Dr. Selmaj has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Celgene, Novartis, Merck, Roche. Dr. Vermersch has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Almirall, Biogen, Celgene, Merck, Novartis, Roche, Sanofi, Servier, and Teva. Dr. Vermersch has received research support from Almirall, Biogen, Celgene, Merck, 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 Acorda, Bayer, Biogen, EMD Serono, Genzyme, Novartis, Questcor, Receptos, Genentech/Roche, Teva. Dr. Margolin has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi. Dr. Chung 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 Employee of Sanofi. Dr. Chirieac has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi. Dr. Coles has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sanofi.