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Clinical Trial
. 2017 Jan 19;376(3):221-234.
doi: 10.1056/NEJMoa1601277. Epub 2016 Dec 21.

Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis

Stephen L Hauser  1 , Amit Bar-Or  1 , Giancarlo Comi  1 , Gavin Giovannoni  1 , Hans-Peter Hartung  1 , Bernhard Hemmer  1 , Fred Lublin  1 , Xavier Montalban  1 , Kottil W Rammohan  1 , Krzysztof Selmaj  1 , Anthony Traboulsee  1 , Jerry S Wolinsky  1 , Douglas L Arnold  1 , Gaelle Klingelschmitt  1 , Donna Masterman  1 , Paulo Fontoura  1 , Shibeshih Belachew  1 , Peter Chin  1 , Nicole Mairon  1 , Hideki Garren  1 , Ludwig Kappos  1 ; OPERA I and OPERA II Clinical Investigators
Collaborators, Affiliations
Free article
Clinical Trial

Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis

Stephen L Hauser et al. N Engl J Med. .
Free article

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.).

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