OBJECTIVES: We present the first study to explore safety and efficacy of the 
human CD20 monoclonal antibody ofatumumab in relapsing-remitting multiple 
sclerosis (RRMS).
METHODS: In this randomized, double-blind, placebo-controlled study, patients 
received 2 ofatumumab infusions (100 mg, 300 mg, or 700 mg) or placebo 2 weeks 
apart. At week 24, patients received alternate treatment. Safety and efficacy 
were assessed.
RESULTS: Thirty-eight patients were randomized (ofatumumab/placebo, n = 26; 
placebo/ofatumumab, n = 12) and analyzed; 36 completed the study. Two patients 
in the 300-mg group withdrew from the study because of adverse events. No 
unexpected safety signals emerged. Infusion-related reactions were common on the 
first infusion day but not observed on the second infusion day. None of the 
patients developed human anti-human antibodies. Ofatumumab was associated with 
profound selective reduction of B cells as measured by CD19(+) expression. New 
brain MRI lesion activity was suppressed (>99%) in the first 24 weeks after 
ofatumumab administration (all doses), with statistically significant reductions 
(p < 0.001) favoring ofatumumab found in new T1 gadolinium-enhancing lesions, 
total enhancing T1 lesions, and new and/or enlarging T2 lesions.
CONCLUSIONS: Ofatumumab (up to 700 mg) given 2 weeks apart was not associated 
with any unexpected safety concerns and was well tolerated in patients with 
RRMS. MRI data suggest a clinically meaningful effect of ofatumumab for all 
doses studied. Results warrant further exploration of ofatumumab in RRMS.
CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in 
patients with RRMS, ofatumumab compared with placebo does not increase the 
number of serious adverse events and decreases the number of new MRI lesions.