Colin Dayan, MD, PhD
LONDON—Autoimmune adverse events over five years were generally mild or moderate in intensity in alemtuzumab-treated patients from the CARE-MS trials, according to data presented at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). “No patients withdrew from the extension studies due to autoimmune adverse events,” said Colin Dayan, MD, PhD, Clinical Professor, Cardiff University School of Medicine, Cardiff, United Kingdom, and his research colleagues. “Consistent with previous reports, most autoimmune adverse events were thyroid-related events.”
Alemtuzumab significantly improved clinical and MRI outcomes versus subcutaneous interferon beta-1a over two years in patients with relapsing-remitting multiple sclerosis (MS) who were treatment-naive in the CARE-MS I trial or had an inadequate response (ie, one or more relapses) to prior therapy at baseline in the CARE-MS II trial. Durable efficacy over five years was observed in an extension study in the absence of continuous treatment. The most frequent adverse events with alemtuzumab were infusion-associated reactions; other adverse events included autoimmune adverse events. According to researchers, patient education and the drug’s safety monitoring program enable timely detection and treatment of autoimmune adverse events in patients treated with alemtuzumab.
The goal of the present study was to evaluate the occurrence of autoimmune adverse events over five years in patients with relapsing-remitting MS treated with alemtuzumab.
Patients participating in the study received two courses of alemtuzumab 12 mg (Month 0: 5 days; Month 12: 3 days) in the CARE-MS core studies, with as-needed alemtuzumab for relapse or MRI activity in the extension. Patients were monitored for autoimmune adverse events. Safety measures included quarterly thyroid function testing, monthly complete blood counts with platelets and symptom monitoring for immune thrombocytopenia, and monthly serum creatinine and urinalysis.
Results were reported for pooled data from the CARE-MS I and II studies. A total of 811 patients received alemtuzumab 12 mg in the CARE-MS I and II core studies; 742 (91%) entered the extension, and 692 (93%) of those remained in the study at five years. Most autoimmune adverse events were mild or moderate in intensity. Serious autoimmune adverse events were uncommon (67 events; 1.8/100 patient-years over five years). None of the adverse events led to study withdrawal. The most common autoimmune adverse events were thyroid adverse events, the rate of which peaked in Year 3 (227 events; 31.3/100 patient-years) and subsequently declined in Years 4 (126 events; 17.6/100 patient-years) and 5 (95 events; 13.6/100 patient-years). Serious thyroid adverse event rates remained low. Over Years 0-5, 22 immune thrombocytopenia events were observed (cumulative rate: 0.59) with no fatalities. Two nephropathies were reported over Years 0-5 (cumulative rate: 0.05); serum creatinine remained normal in both cases.
This study was supported by Sanofi Genzyme and Bayer HealthCare Pharmaceuticals.
—Glenn S. Williams