Per S Sorensen1, Steen Lisby, Richard Grove, Frederick Derosier, Steve Shackelford, Eva Havrdova, Jelena Drulovic, Massimo Filippi. 1. 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.
Abstract
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.
RCT Entities:
OBJECTIVES: We present the first study to explore safety and efficacy of the humanCD20 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.
Authors: H-Christian von Büdingen; Arumugam Palanichamy; Klaus Lehmann-Horn; Brady A Michel; Scott S Zamvil Journal: Eur Neurol Date: 2015-03-25 Impact factor: 1.710
Authors: Olaf Stüve; Clemens Warnke; Krystin Deason; Martin Stangel; Bernd C Kieseier; Hans-Peter Hartung; Hans-Christian von Büdingen; Diego Centonze; Thomas G Forsthuber; Volker Knappertz Journal: Acta Neuropathol Date: 2014-07-04 Impact factor: 17.088