Alemtuzumab more effective than interferon β-1a at 5-year follow-up of CAMMS223 Clinical Trial

Objective: To report the long-term safety and efficacy results from CAMMS223 comparing alemtuzumab with interferon beta-1a in early, active relapsing-remitting multiple sclerosis (RRMS). What are the long-term effects of alemtuzumab treatment, received 36 to 48 months previously, on relapse and disability in early, active RRMS? This study provides evidence of the effectiveness of alemtuzumab in reducing the relapse rate and accumulation of disability compared with interferon beta-1a (IFN beta-1a) through extended follow-up (up to 60 months from baseline). Methods: Of 334 patients originally randomized, 198 participated in the extension phase (151 [68%] alemtuzumab and 47 [42%] IFN beta-1a). Disability, relapses, and safety were assessed as in the original study period. Efficacy outcomes were analyzed from baseline of the original trial period to 60 months. Safety data extended beyond 60 months. Results: Over 5 years, alemtuzumab lowered the risk of sustained accumulation of disability by 72% and the rate of relapse by 69% compared with IFN beta-1a (both p < 0.0001). The annualized relapse rate from baseline to month 60 was 0.11 for alemtuzumab and 0.35 for IFN beta-1a. Complete safety follow-up reflected 988 and 376 person-years for alemtuzumab and IFN beta-1a patients, respectively. Serious infections were seen in 7% of alemtuzumab patients and 3% of IFN beta-1a patients, and thyroid disorders were seen in 30% of alemtuzumab patients vs 4% of IFN beta-1a patients. Immune thrombocytopenia occurred in 3% of alemtuzumab patients and 0.9% of IFN beta-1a patients during the initial study period; no additional events were reported during the extension phase. One alemtuzumab patient developed Goodpasture disease 39 months after the second annual cycle of alemtuzumab. Conclusions: Through extended follow-up, alemtuzumab remained significantly more efficacious than IFN beta-1a, with a safety profile consistent with previous reports. Classification of Evidence: This study provides Class III evidence that alemtuzumab is more effective than interferon beta-1a in reducing relapses and disability in patients with RRMS in a long-term follow-up of a rater-blinded, randomized clinical trial with 59.5% of patients participating in the extended follow-up period. Neurology (R) 2012;78:1069-1078