Safety and efficacy of ofatumumab in relapsing-remitting multiple sclerosis: a phase 2 study.
OBJECTIVE
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.


METHODS
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.
From the Danish Multiple Sclerosis Center (P.S.S.), Rigshospitalet, Copenhagen; Genmab (S.L.), Copenhagen, Denmark; GlaxoSmithKline (R.G.), Uxbridge, Middlesex, UK; GlaxoSmithKline (F.D.), Research Triangle Park; GlaxoSmithKline (S.S.), Raleigh, NC; Charles University (E.H.), Prague, Czech Republic; School of Medicine University of Belgrade (J.D.), Serbia; and San Raffaele Scientific Institute and Vita-Salute San Raffaele University (M.F.), Milan, Italy.
Per S
PS
Sorensen
Steen
S
Lisby
Richard
R
Grove
Frederick
F
Derosier
Steve
S
Shackelford
Eva
E
Havrdova
Jelena
J
Drulovic
Massimo
M
Filippi
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018941:Antigens, CD19 / Q000096:biosynthesis / Q000276:immunology; D018951:Antigens, CD20 / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D004311:Double-Blind Method; D019317:Evidence-Based Medicine / Q000379:methods / Q000639:trends; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D016896:Treatment Outcome; D055815:Young Adult
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018941:Antigens, CD19; D018951:Antigens, CD20; C527517:ofatumumab