Ocrelizumab in relapsing-remitting multiple sclerosis

A phase 2, randomised, placebo-controlled, multicentre trial

Ludwig Kappos, David Li, Peter Calabresi, Paul O'Connor, Amit Bar-Or, Frederik Barkhof, Ming Yin, David Leppert, Robert Glanzman, Jeroen Tinbergen, Stephen L. Hauser

Research output: Contribution to journalArticle

Abstract

B lymphocytes are implicated in the pathogenesis of multiple sclerosis. We aimed to assess efficacy and safety of two dose regimens of the humanised anti-CD20 monoclonal antibody ocrelizumab in patients with relapsing-remitting multiple sclerosis. We did a multicentre, randomised, parallel, double-blind, placebo-controlled study involving 79 centres in 20 countries. Patients aged 18-55 years with relapsing-remitting multiple sclerosis were randomly assigned (1:1:1:1) via an interactive voice response system to receive either placebo, low-dose (600 mg) or high-dose (2000 mg) ocrelizumab in two doses on days 1 and 15, or intramuscular interferon beta-1a (30 μg) once a week. The randomisation list was not disclosed to the study centres, monitors, project statisticians or to the project team at Roche. All groups were double blinded to group assignment, except the interferon beta-1a group who were rater masked. At week 24, patients in the initial placebo, 600 mg ocrelizumab, and interferon beta-1a groups received ocrelizumab 600 mg; the 2000 mg group received 1000 mg. Our primary endpoint was the total number of gadolinium-enhancing lesions (GEL) and T1-weighted MRI at weeks 12, 16, 20, and 24. Analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT00676715. 218 (99) of the 220 randomised patients received at least one dose of ocrelizumab, 204 (93) completed 24 weeks of the study and 196 (89) completed 48 weeks. In the intention-to-treat population of 218 patients, at week 24, the number of gadolinium-enhancing lesions was 89 (95 CI 68-97; p

Original languageEnglish (US)
Pages (from-to)1779-1787
Number of pages9
JournalThe Lancet
Volume378
Issue number9805
DOIs
StatePublished - Nov 19 2011

Fingerprint

ocrelizumab
Relapsing-Remitting Multiple Sclerosis
Multicenter Studies
Placebos
Gadolinium
Random Allocation
Multiple Sclerosis
B-Lymphocytes
Monoclonal Antibodies
Safety

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ocrelizumab in relapsing-remitting multiple sclerosis : A phase 2, randomised, placebo-controlled, multicentre trial. / Kappos, Ludwig; Li, David; Calabresi, Peter; O'Connor, Paul; Bar-Or, Amit; Barkhof, Frederik; Yin, Ming; Leppert, David; Glanzman, Robert; Tinbergen, Jeroen; Hauser, Stephen L.

In: The Lancet, Vol. 378, No. 9805, 19.11.2011, p. 1779-1787.

Research output: Contribution to journalArticle

Kappos, L, Li, D, Calabresi, P, O'Connor, P, Bar-Or, A, Barkhof, F, Yin, M, Leppert, D, Glanzman, R, Tinbergen, J & Hauser, SL 2011, 'Ocrelizumab in relapsing-remitting multiple sclerosis: A phase 2, randomised, placebo-controlled, multicentre trial', The Lancet, vol. 378, no. 9805, pp. 1779-1787. https://doi.org/10.1016/S0140-6736(11)61649-8
Kappos, Ludwig ; Li, David ; Calabresi, Peter ; O'Connor, Paul ; Bar-Or, Amit ; Barkhof, Frederik ; Yin, Ming ; Leppert, David ; Glanzman, Robert ; Tinbergen, Jeroen ; Hauser, Stephen L. / Ocrelizumab in relapsing-remitting multiple sclerosis : A phase 2, randomised, placebo-controlled, multicentre trial. In: The Lancet. 2011 ; Vol. 378, No. 9805. pp. 1779-1787.
@article{2d5216f6fc4a49a89391fb51a1398df3,
title = "Ocrelizumab in relapsing-remitting multiple sclerosis: A phase 2, randomised, placebo-controlled, multicentre trial",
abstract = "B lymphocytes are implicated in the pathogenesis of multiple sclerosis. We aimed to assess efficacy and safety of two dose regimens of the humanised anti-CD20 monoclonal antibody ocrelizumab in patients with relapsing-remitting multiple sclerosis. We did a multicentre, randomised, parallel, double-blind, placebo-controlled study involving 79 centres in 20 countries. Patients aged 18-55 years with relapsing-remitting multiple sclerosis were randomly assigned (1:1:1:1) via an interactive voice response system to receive either placebo, low-dose (600 mg) or high-dose (2000 mg) ocrelizumab in two doses on days 1 and 15, or intramuscular interferon beta-1a (30 μg) once a week. The randomisation list was not disclosed to the study centres, monitors, project statisticians or to the project team at Roche. All groups were double blinded to group assignment, except the interferon beta-1a group who were rater masked. At week 24, patients in the initial placebo, 600 mg ocrelizumab, and interferon beta-1a groups received ocrelizumab 600 mg; the 2000 mg group received 1000 mg. Our primary endpoint was the total number of gadolinium-enhancing lesions (GEL) and T1-weighted MRI at weeks 12, 16, 20, and 24. Analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT00676715. 218 (99) of the 220 randomised patients received at least one dose of ocrelizumab, 204 (93) completed 24 weeks of the study and 196 (89) completed 48 weeks. In the intention-to-treat population of 218 patients, at week 24, the number of gadolinium-enhancing lesions was 89 (95 CI 68-97; p",
author = "Ludwig Kappos and David Li and Peter Calabresi and Paul O'Connor and Amit Bar-Or and Frederik Barkhof and Ming Yin and David Leppert and Robert Glanzman and Jeroen Tinbergen and Hauser, {Stephen L.}",
year = "2011",
month = "11",
day = "19",
doi = "10.1016/S0140-6736(11)61649-8",
language = "English (US)",
volume = "378",
pages = "1779--1787",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Elsevier Limited",
number = "9805",

}

TY - JOUR

T1 - Ocrelizumab in relapsing-remitting multiple sclerosis

T2 - A phase 2, randomised, placebo-controlled, multicentre trial

AU - Kappos, Ludwig

AU - Li, David

AU - Calabresi, Peter

AU - O'Connor, Paul

AU - Bar-Or, Amit

AU - Barkhof, Frederik

AU - Yin, Ming

AU - Leppert, David

AU - Glanzman, Robert

AU - Tinbergen, Jeroen

AU - Hauser, Stephen L.

PY - 2011/11/19

Y1 - 2011/11/19

N2 - B lymphocytes are implicated in the pathogenesis of multiple sclerosis. We aimed to assess efficacy and safety of two dose regimens of the humanised anti-CD20 monoclonal antibody ocrelizumab in patients with relapsing-remitting multiple sclerosis. We did a multicentre, randomised, parallel, double-blind, placebo-controlled study involving 79 centres in 20 countries. Patients aged 18-55 years with relapsing-remitting multiple sclerosis were randomly assigned (1:1:1:1) via an interactive voice response system to receive either placebo, low-dose (600 mg) or high-dose (2000 mg) ocrelizumab in two doses on days 1 and 15, or intramuscular interferon beta-1a (30 μg) once a week. The randomisation list was not disclosed to the study centres, monitors, project statisticians or to the project team at Roche. All groups were double blinded to group assignment, except the interferon beta-1a group who were rater masked. At week 24, patients in the initial placebo, 600 mg ocrelizumab, and interferon beta-1a groups received ocrelizumab 600 mg; the 2000 mg group received 1000 mg. Our primary endpoint was the total number of gadolinium-enhancing lesions (GEL) and T1-weighted MRI at weeks 12, 16, 20, and 24. Analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT00676715. 218 (99) of the 220 randomised patients received at least one dose of ocrelizumab, 204 (93) completed 24 weeks of the study and 196 (89) completed 48 weeks. In the intention-to-treat population of 218 patients, at week 24, the number of gadolinium-enhancing lesions was 89 (95 CI 68-97; p

AB - B lymphocytes are implicated in the pathogenesis of multiple sclerosis. We aimed to assess efficacy and safety of two dose regimens of the humanised anti-CD20 monoclonal antibody ocrelizumab in patients with relapsing-remitting multiple sclerosis. We did a multicentre, randomised, parallel, double-blind, placebo-controlled study involving 79 centres in 20 countries. Patients aged 18-55 years with relapsing-remitting multiple sclerosis were randomly assigned (1:1:1:1) via an interactive voice response system to receive either placebo, low-dose (600 mg) or high-dose (2000 mg) ocrelizumab in two doses on days 1 and 15, or intramuscular interferon beta-1a (30 μg) once a week. The randomisation list was not disclosed to the study centres, monitors, project statisticians or to the project team at Roche. All groups were double blinded to group assignment, except the interferon beta-1a group who were rater masked. At week 24, patients in the initial placebo, 600 mg ocrelizumab, and interferon beta-1a groups received ocrelizumab 600 mg; the 2000 mg group received 1000 mg. Our primary endpoint was the total number of gadolinium-enhancing lesions (GEL) and T1-weighted MRI at weeks 12, 16, 20, and 24. Analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT00676715. 218 (99) of the 220 randomised patients received at least one dose of ocrelizumab, 204 (93) completed 24 weeks of the study and 196 (89) completed 48 weeks. In the intention-to-treat population of 218 patients, at week 24, the number of gadolinium-enhancing lesions was 89 (95 CI 68-97; p

UR - http://www.scopus.com/inward/record.url?scp=81555202418&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=81555202418&partnerID=8YFLogxK

U2 - 10.1016/S0140-6736(11)61649-8

DO - 10.1016/S0140-6736(11)61649-8

M3 - Article

VL - 378

SP - 1779

EP - 1787

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 9805

ER -