Infusion-Associated Reactions in Patients Receiving Alemtuzumab after Switching from Subcutaneous Interferon Beta-1a

Background:  Alemtuzumab is a humanized anti-CD52 antibody approved for the treatment of relapsing forms of multiple sclerosis (MS). In the CARE-MS I (NCT00530348) and CARE-MS II (NCT00548405) studies, infusion-associated reactions (IARs) occurred in most patients but were predominantly non-serious and effectively managed.

Objectives:  To assess the incidence of IARs in patients who received alemtuzumab in an extension study (NCT00930553) after receiving subcutaneous interferon beta-1a (SC IFNB-1a) in either of the CARE-MS core studies.

Methods:  The phase 3 CARE-MS I and II studies compared SC IFNB-1a (44 μg 3 times per week) with alemtuzumab (12 mg/day on 5 consecutive days at baseline and on 3 consecutive days at month 12) in patients with active relapsing MS. In the extension study, patients previously receiving SC IFNB-1a were switched to alemtuzumab 12 mg/day on 5 consecutive days at start of the extension and on 3 days 12 months later. All patients received prophylactic intravenous methylprednisolone 1 g prior to infusion on the first 3 infusion days of each treatment course. IARs were defined as any adverse event with onset during infusion or up to 24 hours after the end of an infusion. Data were pooled from patients entering the extension from both CARE-MS core studies.

Results:  A total of 282 patients were treated with alemtuzumab in the extension study after receiving SC IFNB-1a in the core studies; 93.3% of patients received 2 alemtuzumab courses. The incidence of IARs declined from Year 1 (83.3%) to Year 2 (43.9%) of the extension study in patients who switched from SC IFNB-1a to alemtuzumab, as was observed during the first 2 years of alemtuzumab treatment in the core studies. IARs were most frequent on the first infusion day of each treatment course. The most frequently reported IARs were rash, headache, pyrexia, nausea, urticaria, and insomnia. Serious IARs were infrequent (Year 1: 0.7%; Year 2: 0.4%).

Conclusions:  Patients who switched from SC IFNB-1a to alemtuzumab in the CARE-MS extension study had similar incidence and severity of IARs as patients who received alemtuzumab in the core studies. These findings support the consistent profile of IARs associated with alemtuzumab infusion across clinical trials.

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