• Stephen L Hauser, Amit Bar-Or, Giancarlo Comi, Gavin Giovannoni, Hans-Peter Hartung, Bernhard Hemmer, Fred Lublin, Xavier Montalban, Kottil W Rammohan, Krzysztof Selmaj, Anthony Traboulsee, Jerry S Wolinsky, Douglas L Arnold, Gaelle Klingelschmitt, Donna Masterman, Paulo Fontoura, Shibeshih Belachew, Peter Chin, Nicole Mairon, Hideki Garren, Ludwig Kappos, and OPERA I and OPERA II Clinical Investigators.
• From the University of California, San Francisco (S.L.H.), and Genentech, South San Francisco (D.M., P.C., H.G.) - both in California; McGill University (A.B.-O., D.L.A.) and NeuroRx Research (D.L.A.), Montreal, and University of British Columbia, Vancouver, BC (A.T.) - both in Canada; University Vita-Salute San Raffaele, Milan (G.C.); Barts and the London School of Medicine and Dentistry, London (G.G.); Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (H.-P.H.), and the Technical University of Munich and Munich Cluster for Systems Neurology, Munich (B.H.) - both in Germany; Icahn School of Medicine at Mount Sinai, New York (F.L.); Hospital Vall d'Hebron University, Barcelona (X.M.); University of Miami, Miami (K.W.R.); Medical University of Lodz and Center for Neurology, Lodz, Poland (K.S.); McGovern Medical School, University of Texas Health Science Center at Houston, Houston (J.S.W.); and F. Hoffmann-La Roche (G.K., P.F., S.B., N.M.) and University Hospital Basel, University of Basel (L.K.), Basel, Switzerland.
• N. Engl. J. Med. 2017 Jan 19; 376 (3): 221-234.

BackgroundB cells influence the pathogenesis of multiple sclerosis. Ocrelizumab is a humanized monoclonal antibody that selectively depletes CD20+ B cells.MethodsIn two identical phase 3 trials, we randomly assigned 821 and 835 patients with relapsing multiple sclerosis to receive intravenous ocrelizumab at a dose of 600 mg every 24 weeks or subcutaneous interferon beta-1a at a dose of 44 μg three times weekly for 96 weeks. The primary end point was the annualized relapse rate.ResultsThe annualized relapse rate was lower with ocrelizumab than with interferon beta-1a in trial 1 (0.16 vs. 0.29; 46% lower rate with ocrelizumab; P<0.001) and in trial 2 (0.16 vs. 0.29; 47% lower rate; P<0.001). In prespecified pooled analyses, the percentage of patients with disability progression confirmed at 12 weeks was significantly lower with ocrelizumab than with interferon beta-1a (9.1% vs. 13.6%; hazard ratio, 0.60; 95% confidence interval [CI], 0.45 to 0.81; P<0.001), as was the percentage of patients with disability progression confirmed at 24 weeks (6.9% vs. 10.5%; hazard ratio, 0.60; 95% CI, 0.43 to 0.84; P=0.003). The mean number of gadolinium-enhancing lesions per T1-weighted magnetic resonance scan was 0.02 with ocrelizumab versus 0.29 with interferon beta-1a in trial 1 (94% lower number of lesions with ocrelizumab, P<0.001) and 0.02 versus 0.42 in trial 2 (95% lower number of lesions, P<0.001). The change in the Multiple Sclerosis Functional Composite score (a composite measure of walking speed, upper-limb movements, and cognition; for this z score, negative values indicate worsening and positive values indicate improvement) significantly favored ocrelizumab over interferon beta-1a in trial 2 (0.28 vs. 0.17, P=0.004) but not in trial 1 (0.21 vs. 0.17, P=0.33). Infusion-related reactions occurred in 34.3% of the patients treated with ocrelizumab. Serious infection occurred in 1.3% of the patients treated with ocrelizumab and in 2.9% of those treated with interferon beta-1a. Neoplasms occurred in 0.5% of the patients treated with ocrelizumab and in 0.2% of those treated with interferon beta-1a.ConclusionsAmong patients with relapsing multiple sclerosis, ocrelizumab was associated with lower rates of disease activity and progression than interferon beta-1a over a period of 96 weeks. Larger and longer studies of the safety of ocrelizumab are required. (Funded by F. Hoffmann-La Roche; OPERA I and II ClinicalTrials.gov numbers, NCT01247324 and NCT01412333 , respectively.).

31 keywords...

hide…