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 Garren & 3 others Ludwig Kappos, OPERA I and OPERA II Clinical Investigators, Diego Centonze

Research output: Contribution to journalArticle

315 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. (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

Fingerprint

ocrelizumab
Multiple Sclerosis
Interferon beta-1a
B-Lymphocytes

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

Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. / Hauser, Stephen L; Bar-Or, Amit; Comi, Giancarlo; Giovannoni, Gavin; Hartung, Hans-Peter; Hemmer, Bernhard; Lublin, Fred; Montalban, Xavier; Rammohan, Kottil W; Selmaj, Krzysztof; Traboulsee, Anthony; Wolinsky, Jerry S; Arnold, Douglas L; Klingelschmitt, Gaelle; Masterman, Donna; Fontoura, Paulo; Belachew, Shibeshih; Chin, Peter; Mairon, Nicole; Garren, Hideki; Kappos, Ludwig; OPERA I and OPERA II Clinical Investigators ; Centonze, Diego.

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

Research output: Contribution to journalArticle

Hauser, SL, Bar-Or, A, Comi, G, Giovannoni, G, Hartung, H-P, Hemmer, B, Lublin, F, Montalban, X, Rammohan, KW, Selmaj, K, Traboulsee, A, Wolinsky, JS, Arnold, DL, Klingelschmitt, G, Masterman, D, Fontoura, P, Belachew, S, Chin, P, Mairon, N, Garren, H, Kappos, L, OPERA I and OPERA II Clinical Investigators & Centonze, D 2017, 'Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis', New England Journal of Medicine, vol. 376, no. 3, pp. 221-234. https://doi.org/10.1056/NEJMoa1601277
Hauser, Stephen L ; Bar-Or, Amit ; Comi, Giancarlo ; Giovannoni, Gavin ; Hartung, Hans-Peter ; Hemmer, Bernhard ; Lublin, Fred ; Montalban, Xavier ; Rammohan, Kottil W ; Selmaj, Krzysztof ; Traboulsee, Anthony ; Wolinsky, Jerry S ; Arnold, Douglas L ; Klingelschmitt, Gaelle ; Masterman, Donna ; Fontoura, Paulo ; Belachew, Shibeshih ; Chin, Peter ; Mairon, Nicole ; Garren, Hideki ; Kappos, Ludwig ; OPERA I and OPERA II Clinical Investigators ; Centonze, Diego. / Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. In: New England Journal of Medicine. 2017 ; Vol. 376, No. 3. pp. 221-234.
@article{8e00ba895879465dbb698cfaf88ef300,
title = "Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis",
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.).",
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",
author = "Hauser, {Stephen L} and Amit Bar-Or and Giancarlo Comi and Gavin Giovannoni and Hans-Peter Hartung and Bernhard Hemmer and Fred Lublin and Xavier Montalban and Rammohan, {Kottil W} and Krzysztof Selmaj and Anthony Traboulsee and Wolinsky, {Jerry S} and Arnold, {Douglas L} and Gaelle Klingelschmitt and Donna Masterman and Paulo Fontoura and Shibeshih Belachew and Peter Chin and Nicole Mairon and Hideki Garren and Ludwig Kappos and {OPERA I and OPERA II Clinical Investigators} and Diego Centonze",
year = "2017",
month = "1",
day = "19",
doi = "10.1056/NEJMoa1601277",
language = "English",
volume = "376",
pages = "221--234",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "3",

}

TY - JOUR

T1 - Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis

AU - Hauser, Stephen L

AU - Bar-Or, Amit

AU - Comi, Giancarlo

AU - Giovannoni, Gavin

AU - Hartung, Hans-Peter

AU - Hemmer, Bernhard

AU - Lublin, Fred

AU - Montalban, Xavier

AU - Rammohan, Kottil W

AU - Selmaj, Krzysztof

AU - Traboulsee, Anthony

AU - Wolinsky, Jerry S

AU - Arnold, Douglas L

AU - Klingelschmitt, Gaelle

AU - Masterman, Donna

AU - Fontoura, Paulo

AU - Belachew, Shibeshih

AU - Chin, Peter

AU - Mairon, Nicole

AU - Garren, Hideki

AU - Kappos, Ludwig

AU - OPERA I and OPERA II Clinical Investigators

AU - Centonze, Diego

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. (Funded by F. Hoffmann-La Roche; OPERA I and II ClinicalTrials.gov numbers, NCT01247324 and NCT01412333 , respectively.).

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. (Funded by F. Hoffmann-La Roche; OPERA I and II ClinicalTrials.gov numbers, NCT01247324 and NCT01412333 , respectively.).

KW - Adult

KW - Antibodies, Monoclonal, Humanized

KW - Antigens, CD20

KW - B-Lymphocytes

KW - Brain

KW - Disease Progression

KW - Female

KW - Humans

KW - Immunologic Factors

KW - Infusions, Intravenous

KW - Interferon-beta

KW - Magnetic Resonance Imaging

KW - Male

KW - Middle Aged

KW - Multiple Sclerosis, Relapsing-Remitting

KW - Recurrence

KW - Clinical Trial, Phase III

KW - Comparative Study

KW - Journal Article

KW - Multicenter Study

KW - Randomized Controlled Trial

KW - Research Support, Non-U.S. Gov't

U2 - 10.1056/NEJMoa1601277

DO - 10.1056/NEJMoa1601277

M3 - Article

VL - 376

SP - 221

EP - 234

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 3

ER -