Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis

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 GarrenLudwig Kappos, OPERA I and OPERA II Clinical Investigators, Diego Centonze

Research output: Contribution to journalArticle

Abstract

BACKGROUND: B cells influence the pathogenesis of multiple sclerosis. Ocrelizumab is a humanized monoclonal antibody that selectively depletes CD20+ B cells.

METHODS: In 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.

RESULTS: The 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.

CONCLUSIONS: Among 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.).

Original languageEnglish
Pages (from-to)221-234
Number of pages14
JournalNew England Journal of Medicine
Volume376
Issue number3
DOIs
Publication statusPublished - Jan 19 2017

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Keywords

  • Adult
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD20
  • B-Lymphocytes
  • Brain
  • Disease Progression
  • Female
  • Humans
  • Immunologic Factors
  • Infusions, Intravenous
  • Interferon-beta
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting
  • Recurrence
  • Clinical Trial, Phase III
  • Comparative Study
  • Journal Article
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

Cite this

Hauser, S. L., Bar-Or, A., Comi, G., Giovannoni, G., Hartung, H-P., Hemmer, B., Lublin, F., Montalban, X., Rammohan, K. W., Selmaj, K., Traboulsee, A., Wolinsky, J. S., Arnold, D. L., Klingelschmitt, G., Masterman, D., Fontoura, P., Belachew, S., Chin, P., Mairon, N., ... Centonze, D. (2017). Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. New England Journal of Medicine, 376(3), 221-234. https://doi.org/10.1056/NEJMoa1601277