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)

Abstract

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-naïve (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