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Thyroid Autoimmune Adverse Events in Patients Treated with Alemtuzumab for Relapsing-remitting Multiple Sclerosis: Four-year Follow-up of the CARE-MS Studies (P2.199)

2014; Lippincott Williams & Wilkins; Volume: 82; Issue: 10_supplement Linguagem: Inglês

10.1212/wnl.82.10_supplement.p2.199

1526-632X

Cary Twyman, Pedro Oyuela, Jeffrey Palmer, David Margolin, Colin Dayan,

Liver Diseases and Immunity

OBJECTIVE: Summarize incidence and timing of thyroid autoimmune adverse events (AEs) in the ongoing CARE-MS extension study (as of July 15, 2013). BACKGROUND: Three clinical trials (CAMMS223, CARE-MS I, and CARE-MS II) in active relapsing-remitting multiple sclerosis (RRMS) patients demonstrated superior clinical efficacy for alemtuzumab versus subcutaneous interferon beta-1a (SC IFNB-1a); efficacy improvements were sustained in the first additional year of the CARE-MS extension phase. Alemtuzumab’s consistent safety profile includes an identified risk of autoimmune AEs, most frequently thyroid disorders. DESIGN/METHODS: In the 2-year core CARE-MS studies, RRMS patients who were treatment-naive (CARE-MS I) or who relapsed on prior therapy (CARE-MS II) received alemtuzumab 12 mg/day IV infusions on 5 consecutive days at baseline and 3 consecutive days 12 months later. In the extension, former alemtuzumab-treated patients were eligible for additional alemtuzumab (12 mg/day IV for 3 days) on evidence of disease activity. As part of a comprehensive monitoring program, thyroid function testing was performed at baseline and quarterly thereafter. RESULTS: Complete Year 4 data were available for 563 (77%) of prior alemtuzumab patients who entered Year 4 of extension (N=729). During Years 0-4, thyroid events were reported in 35% (285/811) of patients; most were Grade 1 or 2 in severity; 3.5% had serious thyroid events. All thyroid cases except 1 had first thyroid abnormality detected within 48 months from last dose. The proportion of patients with thyroid events peaked at Year 3 and subsequently declined (Y1: 5.7%; Y2: 10.7%; Y3: 20.7%; Y4: 9.4%). Thyroid events were not correlated with cumulative exposure; none resulted in study discontinuation. Most events were managed with first-line, conventional therapy; few patients underwent thyroidectomy. CONCLUSIONS: The incidence of thyroid AEs peaked at 36 months in alemtuzumab patients. Ongoing patient education and laboratory monitoring continue to enable timely detection and treatment of alemtuzumab-associated thyroid events. Study Supported by: Genzyme, a Sanofi company, and Bayer Healthcare Pharmaceuticals Disclosure: Dr. Twyman has received personal compensation for activities with Genzyme Corp., Sanofi-Aventis Pharmaceuticals Inc., Eli Lilly & Co., Opexa Therapeutics, Biogen Idec, Teva Neuroscience, Roche Diagnostics Corp., Novartis, Xenoport, Acorda Therapeutics, and Pfizer Inc. Dr. Twyman has received research support from Genzyme Corp. Dr. Oyuela has received personal compensation for activities with Genzyme Corporation as an employee. Mr. Palmer has received personal compensation for activities with Genzyme Corporation as an employee. Dr. Margolin has received personal compensation for activities with Genzyme Corp. as an employee. Dr. Dayan has received personal compensation for activities with Genzyme Corp. as a speaker and advisory board member.