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<0.0001), corresponding to a 54·9% 
improvement with alemtuzumab. Based on Kaplan-Meier estimates, 59% of patients 
in the interferon beta 1a group were relapse-free at 2 years compared with 78% 
of patients in the alemtuzumab group (p<0·0001). 20 (11%) of patients in the 
interferon beta 1a group had sustained accumulation of disability compared with 
30 (8%) in the alemtuzumab group (hazard ratio 0·70 [95% CI 0·40-1·23]; p=0·22). 
338 (90%) of patients in the alemtuzumab group had infusion-associated 
reactions; 12 (3%) of which were regarded as serious. Infections, predominantly 
of mild or moderate severity, occurred in 253 (67%) patients treated with 
alemtuzumab versus 85 (45%) patients treated with interferon beta 1a. 62 (16%) 
patients treated with alemtuzumab had herpes infections (predominantly 
cutaneous) compared with three (2%) patients treated with interferon beta 1a. By 
24 months, 68 (18%) patients in the alemtuzumab group had thyroid-associated 
adverse events compared with 12 (6%) in the interferon beta 1a group, and three 
(1%) had immune thrombocytopenia compared with none in the interferon beta 1a 
group. Two patients in the alemtuzumab group developed thyroid papillary 
carcinoma.
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.