Information for Healthcare Professionals

Has the medication received US Food and Drug Administration (FDA) approval? If so, what are the indications and uses? Yes . On November 14, 2014, the FDA approved alemtuzumab for treatment of relapsing forms of multiple sclerosis (MS). Because of its safety profile, alemtuzumab should generally be reserved for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS. What were the findings in the pivotal and supportive trials of this medication? Two Phase III trials were performed comparing intravenous alemtuzumab with subcutaneous interferon beta-1a (Rebif) 44 mcg tiw. One of these was done in a treatment-naïve MS population, and the other was in MS patients who had breakthrough disease on another disease-modifying therapy (DMT) for MS. Both studies were published in The Lancet on November 24, 2012. CARE-MS I trial ( Cohen JA et al, 2012 ) Trial design: This 2-year randomized, rater-blinded trial compared alemtuzumab 12 mg with subcutaneous interferon beta-1a in 581 treatment-naïve MS patients. Patients were 18 to 50 years old, with an Expanded Disability Status Scale (EDSS) of 3.0 or less, who had at least two relapses within the past 2 years, at least one relapse within the past year, and an abnormal brain MRI consistent with MS. Given the very different side-effect profiles and route/frequency of administration of the two drugs, only the neurologic rater was blinded to the treatment assignment. Results: Relapse rate and 6-month sustained disability progression were the co-primary endpoints for the CARE-MS I study. Relapses were defined as new or worsening neurologic symptoms due to MS occurring in the absence of fever, lasting over 48 hours, occurring after 30 days of neurologic stability, and causing new findings on neurologic examination. A blinded relapse adjudication committee confirmed relapses. In CARE-MS I, there was a 54.9% relative reduction (p<0.001) in the relapse rate in the alemtuzumab arm (0.18) compared with the interferon arm (0.39). Sustained disability progression was defined as an increase in EDSS by 1 point (or 1.5 points if initial EDSS was zero) that persisted for 6 months. Eleven percent of patients on interferon beta-1a had sustained disability progression, while only 8% of patients on alemtuzumab had sustained progression; however, this difference was not statistically significant. The alemtuzumab group had fewer patients with new or enhancing lesions on MRI; this effect was greater in the second year of the study. Patients on alemtuzumab also had less brain volume loss on MRI, and both groups had a slight improvement in the EDSS disability score. Thirty-nine percent of the patients receiving alemtuzumab had freedom from clinical and radiographic disease activity, while only 27% of patients in the interferon arm did. CARE-MS II trial ( Coles AJ et al, 2012 ) Trial design: This 2-year randomized, rater-blinded trial compared alemtuzumab 12 mg with subcutaneous interferon beta-1a in 667 MS patients who experienced breakthrough disease after 6 months of being on another DMT (primarily interferon-beta or glatiramer acetate). Patients were between 18 and 55 years of age with an EDSS of 5.0 or lower who had at least two relapses within the past 2 years, at least one relapse within the past year, and an abnormal brain MRI consistent with MS. As above, only the neurologic rater was blinded to treatment assignment due to the very different side-effect profiles and route/frequency of administration of the drugs. Results: Relapse rate and 6-month sustained disability progression were coprimary endpoints for the CARE-MS II study. Relapses were defined as above and were confirmed by a blinded relapse adjudication committee. In CARE-MS II, there was a 49.4% relative reduction in the relapse rate in the alemtuzumab arm (annual rate of 0.26 vs 0.52, p<0.0001) compared with the interferon arm. Sustained disability progression was defined as an increase of EDSS by 1 point (or 1.5 points if initial EDSS was zero) that persisted for 6 months. The alemtuzumab group had a 42% reduction (p=0.0084) in sustained disability progression compared with the interferon group. The alemtuzumab group had fewer patients with new or enhancing lesions on MRI; this effect was greater in the second year of the study. Measurements of new MRI lesions, gadoliniumenhancing lesions, and brain volume also favored alemtuzumab. The alemtuzumab group had a mild improvement in EDSS, while the interferon group declined somewhat on this scale. More patients in the alemtuzumab arm (32% vs 14%) were free of clinical and radiographic disease activity.