Adverse event profile of alemtuzumab in active relapsing remitting multiple sclerosis patients who participated in the CARE‐MS studies: three‐year follow‐up

BACKGROUND:Two phase 3, head-to-head trials comparing alemtuzumab with subcutaneous interferon β-1a (SC IFNB-1a) in relapsing-remitting multiple sclerosis (RRMS) patients who were treatment-naïve (CARE-MS I, NCT00530348) or had disease activity during treatment with disease-modifying therapy (CARE-MS II, NCT00548405) demonstrated durable improvements in relapse rate and disability for alemtuzumab through 3 years. OBJECTIVE:Examine alemtuzumab’s safety in CARE-MS patients who continued in the ongoing extension. METHODS:In the CARE-MS studies, patients were randomized to alemtuzumab (12 mg/day intravenously [IV] on 5 consecutive days at study start and on 3 consecutive days 12 months later) or IFNB-1a (44 mcg SC 3 times weekly). In the extension, former alemtuzumab patients were eligible for additional alemtuzumab (12 mg/day alemtuzumab IV for 3 days) on evidence of clinical or MRI disease activity. Safety ascertainment included clinical and laboratory monitoring. RESULTS:929 patients who received alemtuzumab during the core CARE-MS studies were followed up. Most of the former alemtuzumab 12 mg-treated patients did not receive re-treatment during Year 3 (CARE-MS I, 82%; CARE-MS II, 80%). Nature and severity of AEs in Year 3 were similar to those in Years 1–2; most were mild to moderate and responded to standard treatment. Of patients who received alemtuzumab re-treatment in Year 3, 66% experienced infusion-associated reactions (IARs). 50.3% of extension patients who received alemtuzumab previously experienced infections (vs. 67% and 77% in each core study). The most common infections were nasopharyngitis, upper respiratory, urinary tract, and sinusitis. Most infections were mild to moderate and responded to standard treatment. As previously reported, 1 death occurred in Year 3 (from sepsis). Autoimmune disorders with onset during Year 3 included thyroid disease (19.4%), immune thrombocytopenia (0.4%), and nephropathy (0.1%) (cumulative incidences over 3 years: 29.9%, 1.3% and 0.3%, respectively). CONCLUSIONS:The safety profile of alemtuzumab in the third year of follow-up was consistent with the core CARE-MS studies (IARs being common but manageable, a low incidence of serious infections). The incidence of secondary autoimmunity increased in comparison to Year 2, consistent with what had been observed in prior studies. Patient education and monitoring were important for early detection and treatment of autoimmune disorders