Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial.
Publication/Presentation Date
11-24-2012
Abstract
BACKGROUND: The anti-CD52 monoclonal antibody alemtuzumab reduced disease activity in a phase 2 trial of previously untreated patients with relapsing-remitting multiple sclerosis. We aimed to assess efficacy and safety of first-line alemtuzumab compared with interferon beta 1a in a phase 3 trial.
METHODS: In our 2 year, rater-masked, randomised controlled phase 3 trial, we enrolled adults aged 18-50 years with previously untreated relapsing-remitting multiple sclerosis. Eligible participants were randomly allocated in a 2:1 ratio by an interactive voice response system, stratified by site, to receive intravenous alemtuzumab 12 mg per day or subcutaneous interferon beta 1a 44 μg. Interferon beta 1a was given three-times per week and alemtuzumab was given once per day for 5 days at baseline and once per day for 3 days at 12 months. Coprimary endpoints were relapse rate and time to 6 month sustained accumulation of disability in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00530348.
FINDINGS: 187 (96%) of 195 patients randomly allocated interferon beta 1a and 376 (97%) of 386 patients randomly allocated alemtuzumab were included in the primary analyses. 75 (40%) patients in the interferon beta 1a group relapsed (122 events) compared with 82 (22%) patients in the alemtuzumab group (119 events; rate ratio 0·45 [95% CI 0·32-0·63]; p
INTERPRETATION: Alemtuzumab's consistent safety profile and benefit in terms of reductions of relapse support its use for patients with previously untreated relapsing-remitting multiple sclerosis; however, benefit in terms of disability endpoints noted in previous trials was not observed here.
FUNDING: Genzyme (Sanofi) and Bayer Schering Pharma.
Volume
380
Issue
9856
First Page
1819
Last Page
1828
ISSN
1474-547X
Published In/Presented At
Cohen, J. A., Coles, A. J., Arnold, D. L., Confavreux, C., Fox, E. J., Hartung, H. P., Havrdova, E., Selmaj, K. W., Weiner, H. L., Fisher, E., Brinar, V. V., Giovannoni, G., Stojanovic, M., Ertik, B. I., Lake, S. L., Margolin, D. H., Panzara, M. A., Compston, D. A., & CARE-MS I investigators (2012). Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet (London, England), 380(9856), 1819–1828. https://doi.org/10.1016/S0140-6736(12)61769-3
Disciplines
Medicine and Health Sciences
PubMedID
23122652
Department(s)
Department of Medicine
Document Type
Article