Incidence of Infusion-Associated Reactions Decreases with Subsequent Courses of Alemtuzumab: 5-Year Data from the Care-MS Extension Study

Background: In patients with active RRMS who were treatment-naive (CARE-MS I; NCT00530348) or who had an inadequate response (≥1 relapse) to prior therapy at baseline (CARE-MS II; NCT00548405), infusion-associated reactions (IARs) were the most common adverse events (AEs) following treatment with alemtuzumab.

Objectives: To report on IARs during 5-year follow-up in the ongoing CARE-MS extension study (NCT00930553).

Methods: Patients received 2 annual courses of alemtuzumab 12 mg in the core CARE-MS studies and as-needed alemtuzumab retreatment for relapse or MRI lesion activity in the extension. Methylprednisolone was given on the first 3 days of each course. IARs were any AEs occurring between the start of infusion and within 24 hours after the end of infusion. IAR incidence was based on the number of treated patients in each treatment course. Effective IAR management included measures before (patient education and premedication), during (monitoring, symptomatic treatment, and infusion interruption/rate adjustment), and after infusion (monitoring for ≥2 hours and symptomatic treatment [antihistamines, antipyretics, and/or antiemetics]).

Results: Of 811 patients receiving alemtuzumab in the core studies, 742 entered the extension. Over 5 years, 63% received only 2 initial treatment courses; 26%, 9%, and 1% received 3, 4, and 5 courses. IARs were most common in Course 1 (85%; 687/811 patients) versus Courses 2 (69%; 543/791), 3 (65%; 173/268), 4 (63%; 49/78), and 5 (46%; 5/11). The number of IARs decreased on subsequent infusion days versus Day 1 infusion. The most common IARs were headache (≤36% per course), rash (≤36% per course), and pyrexia (≤18% per course). Serious IARs were reported in 2%, 1%, 1%, 0%, and 0% in Courses 1, 2, 3, 4, and 5. IARs were predominantly mild to moderate; none led to study withdrawal or death. There was one confirmed anaphylaxis event; it resolved with treatment. Few patients required infusion interruption or adjustment.

Conclusions: IARs were common with alemtuzumab, but decreased after Course 1 and were infrequently serious. Incidence peaked on Day 1 of each course. IARs were managed with pretreatment, patient education, appropriate symptomatic medication, monitoring, and adjustment of rate of infusion.

Study supported by Genzyme, a Sanofi company, and Bayer Healthcare Pharmaceuticals.