Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis

OPERA I and OPERA II Clinical Investigators

Research output: Contribution to journalArticle

375 Citations (Scopus)

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.

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

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ocrelizumab
Multiple Sclerosis
Interferon beta-1a
B-Lymphocytes

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Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. / OPERA I and OPERA II Clinical Investigators.

In: New England Journal of Medicine, Vol. 376, No. 3, 19.01.2017, p. 221-234.

Research output: Contribution to journalArticle

OPERA I and OPERA II Clinical Investigators. / Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. In: New England Journal of Medicine. 2017 ; Vol. 376, No. 3. pp. 221-234.
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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.",
author = "{OPERA I and OPERA II Clinical Investigators} and Hauser, {S. L.} and A. Bar-Or and G. Comi and G. Giovannoni and Hartung, {H. P.} and B. Hemmer and F. Lublin and X. Montalban and Rammohan, {Kottil W} and K. Selmaj and A. Traboulsee and Wolinsky, {J. S.} and Arnold, {D. L.} and G. Klingelschmitt and D. Masterman and P. Fontoura and S. Belachew and P. Chin and N. Mairon and H. Garren and L. Kappos",
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TY - JOUR

T1 - Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis

AU - OPERA I and OPERA II Clinical Investigators

AU - Hauser, S. L.

AU - Bar-Or, A.

AU - Comi, G.

AU - Giovannoni, G.

AU - Hartung, H. P.

AU - Hemmer, B.

AU - Lublin, F.

AU - Montalban, X.

AU - Rammohan, Kottil W

AU - Selmaj, K.

AU - Traboulsee, A.

AU - Wolinsky, J. S.

AU - Arnold, D. L.

AU - Klingelschmitt, G.

AU - Masterman, D.

AU - Fontoura, P.

AU - Belachew, S.

AU - Chin, P.

AU - Mairon, N.

AU - Garren, H.

AU - Kappos, L.

PY - 2017/1/19

Y1 - 2017/1/19

N2 - 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.

AB - 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.

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