Safety of Using Disease-Modifying Therapy Post-Alemtuzumab Treatment in Patients with Active Relapsing-Remitting Multiple Sclerosis in the Alemtuzumab Clinical Development Program (P6.185)

OBJECTIVE: To examine safety of disease-modifying therapy (DMT) use post-alemtuzumab in the clinical development program. BACKGROUND: Because alemtuzumab treatment is associated with long-term effects on the immune system, it is important to investigate how subsequent DMT use is tolerated in alemtuzumab-treated patients. DESIGN/METHODS: In phase 2 (CAMMS223 [NCT00050778]) and phase 3 (CARE-MS I [NCT00530348], CARE-MS II [NCT00548405]) studies, patients with active relapsing-remitting MS received 2 annual courses of alemtuzumab (up to 3 courses in CAMMS223) or SC IFNB-1a. In an extension study (NCT00930553), patients initially randomized to SC IFNB-1a could switch to alemtuzumab treatment, and those initially randomized to alemtuzumab could receive as-needed alemtuzumab retreatment for relapse or radiological activity. Use of other DMTs was permitted in the extension at the investigator’s discretion. RESULTS: As of October 4, 2014, DMT use post-alemtuzumab was reported in 119 (8.0[percnt]) of 1486 patients who received alemtuzumab in the core or extension studies. DMT use included glatiramer acetate (GA, n=52), IFNB-1a and -1b (n=37), dimethyl fumarate (n=21), fingolimod (n=17), rituximab (n=13), natalizumab (n=11), teriflunomide (n=5), and mitoxantrone (n=3). Total follow-up after DMT initiation was 307 person-years, most of which occurred with GA (150 person-years) and IFNB-1a and -1b (124 person-years). Proportions of patients with infections (64.7[percnt]), thyroid adverse events (16.8[percnt]), and malignancies (0.8[percnt]) were not increased in patients receiving DMT post-alemtuzumab versus all alemtuzumab-treated patients. Serious infections (7.6[percnt]) or serious thyroid adverse events (2.5[percnt]) were also not increased in patients who received DMT post-alemtuzumab. CONCLUSIONS: The safety profile thus far of DMT use post-alemtuzumab was generally consistent with that observed in all alemtuzumab-treated patients in phase 2 and 3 studies and the extension. Further real-world experience is needed for thorough safety assessment of DMT use post-alemtuzumab. STUDY SUPPORTED BY: Genzyme, a Sanofi company, and Bayer Healthcare Pharmaceuticals. Disclosure: Dr. Bass has received personal compensation for activities with Sanofi-Genzyme, Novartis, Teva Neuroscience, Biogen Idec, Ascend Therapeutics, Quest. Dr. Edwards has received research support from Actelion, Biogen, Eisai, Eli Lilly, Forum Pharmaceuticals, Genentech, Genzyme/Sanofi, Hoffmann-La Roche, Merz Pharmaceuticals, Novartis, Pfizer, and Vaccinex. Dr. Khatri has received personal compensation for activities with Novartis, Teva, Mallinckrodt Pharmaceuticals, Genzyme, Biogen, Acorda, Serono, Pfizer, Bayer, and Avanir. Dr. Selmaj has received personal compensation for activities with Biogen Idec, Novartis, TEVA Pharmaceuticals, Roche Diagnostics Corporation, Genzyme, Synthon, Receptos, and Bayer for serving on the Scientific Advisory Board. Dr. Margolin has received personal compensation for activities with Genzyme as an employee. Dr. Kasten has received personal compensation for activities with PROMETRIKA as an employee. Dr. Soelberg-Sorensen has received personal compensation for activities with Biogen Idec, Merck Serono, Novartis, Genmab, Teva, Elan, and GlaxoSmithKline, Inc.