BACKGROUND: B lymphocytes are implicated in the pathogenesis of multiple 
sclerosis. We aimed to assess efficacy and safety of two dose regimens of the 
humanised anti-CD20 monoclonal antibody ocrelizumab in patients with 
relapsing-remitting multiple sclerosis.
METHODS: We did a multicentre, randomised, parallel, double-blind, 
placebo-controlled study involving 79 centres in 20 countries. Patients aged 
18-55 years with relapsing-remitting multiple sclerosis were randomly assigned 
(1:1:1:1) via an interactive voice response system to receive either placebo, 
low-dose (600 mg) or high-dose (2000 mg) ocrelizumab in two doses on days 1 and 
15, or intramuscular interferon beta-1a (30 μg) once a week. The randomisation 
list was not disclosed to the study centres, monitors, project statisticians or 
to the project team at Roche. All groups were double blinded to group 
assignment, except the interferon beta-1a group who were rater masked. At week 
24, patients in the initial placebo, 600 mg ocrelizumab, and interferon beta-1a 
groups received ocrelizumab 600 mg; the 2000 mg group received 1000 mg. Our 
primary endpoint was the total number of gadolinium-enhancing lesions (GEL) and 
T1-weighted MRI at weeks 12, 16, 20, and 24. Analyses were done on an 
intention-to-treat basis. This trial is registered with ClinicalTrials.gov, 
number NCT00676715.
FINDINGS: 218 (99%) of the 220 randomised patients received at least one dose of 
ocrelizumab, 204 (93%) completed 24 weeks of the study and 196 (89%) completed 
48 weeks. In the intention-to-treat population of 218 patients, at week 24, the 
number of gadolinium-enhancing lesions was 89% (95% CI 68-97; p<0·0001) lower in 
the 600 mg ocrelizumab group than in the placebo group, and 96% (89-99; 
p<0·0001) lower in the 2000 mg group. In exploratory analyses, both 600 mg and 
2000 mg ocrelizumab groups were better than interferon beta-1a for GEL 
reduction. We noted serious adverse events in two of 54 (4%; 95% CI 3·0-4·4) 
patients in the placebo group, one of 55 (2%; 1·3-2·3) in the 600 mg ocrelizumab 
group, three of 55 (5%; 4·6-6·3) in the 2000 mg group, and two of 54 (4%; 
3·0-4·4) in the interferon beta-1a group.
INTERPRETATION: The similarly pronounced effects of B-cell depletion with both 
ocrelizumab doses on MRI and relapse-related outcomes support a role for B-cells 
in disease pathogenesis and warrant further assessment in large, long-term 
trials.
FUNDING: F Hoffmann-La Roche Ltd, Biogen Idec Inc.