Effects of oral glatiramer acetate on clinical and MRI-monitored disease activity in patients with relapsing multiple sclerosis: A multicentre, double-blind, randomised, placebo-controlled study

Massimo Filippi, Jerry S. Wolinsky, Giancarlo Comi

Research output: Contribution to journalArticle

Abstract

Background: Parenterally administered glatiramer acetate reduces the frequency of relapses and the formation of active brain lesions seen with MRI in multiple sclerosis. This study assessed whether two doses of glatiramer acetate given orally could improve clinical and MRI measures of inflammation and neurodegeneration in a large cohort of patients with relapsing-remitting multiple sclerosis. Methods: 1912 patients with relapsing-remitting multiple sclerosis were screened and 1651 were randomised to receive 50 mg or 5 mg of glatiramer acetate or placebo by daily oral administration over 14 months. The intention-to-treat cohort consisted of 1644 patients who took at least one dose of study medication (50 mg glatiramer acetate [n=543], 5 mg glatiramer acetate [n=553], placebo [n=548]). After baseline investigation, clinical assessments were done every 2 months and MRI was obtained for all patients at baseline and at study exit. Additionally, MRI was undertaken every 2 months for a cohort of 486 patients. The primary outcome was the total number of confirmed relapses observed during the study period. Several prespecified clinical and MRI secondary and tertiary outcomes assessed treatment efficacy on inflammation and neurodegeneration due to multiple sclerosis. Findings: The cumulative number of confirmed relapses did not differ between the two active treatment groups and the placebo group. Relative to placebo, the rate ratio for the 50 mg glatiramer acetate treated group was 0·92 (95% CI 0·77-1·08, p=0·30) and for the 5 mg glatiramer acetate treated group was 0·98 (0·83-1·15, p=0·76). No drug effect was seen for any of the secondary and tertiary endpoints. The study drug was safe and well tolerated. Interpretation: 5 mg and 50 mg glatiramer acetate administered orally on a daily basis do not affect relapse rate or other clinical and MRI parameters of disease activity and burden in patients with relapsing-remitting multiple sclerosis. Treatment with oral formulations of glatiramer acetate at the doses tested cannot be recommended.

Original languageEnglish
Pages (from-to)213-220
Number of pages8
JournalThe Lancet Neurology
Volume5
Issue number3
DOIs
Publication statusPublished - Mar 2006

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Multiple Sclerosis
Placebos
Relapsing-Remitting Multiple Sclerosis
Recurrence
Inflammation
Glatiramer Acetate
Pharmaceutical Preparations
Oral Administration
Brain
Therapeutics

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

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title = "Effects of oral glatiramer acetate on clinical and MRI-monitored disease activity in patients with relapsing multiple sclerosis: A multicentre, double-blind, randomised, placebo-controlled study",
abstract = "Background: Parenterally administered glatiramer acetate reduces the frequency of relapses and the formation of active brain lesions seen with MRI in multiple sclerosis. This study assessed whether two doses of glatiramer acetate given orally could improve clinical and MRI measures of inflammation and neurodegeneration in a large cohort of patients with relapsing-remitting multiple sclerosis. Methods: 1912 patients with relapsing-remitting multiple sclerosis were screened and 1651 were randomised to receive 50 mg or 5 mg of glatiramer acetate or placebo by daily oral administration over 14 months. The intention-to-treat cohort consisted of 1644 patients who took at least one dose of study medication (50 mg glatiramer acetate [n=543], 5 mg glatiramer acetate [n=553], placebo [n=548]). After baseline investigation, clinical assessments were done every 2 months and MRI was obtained for all patients at baseline and at study exit. Additionally, MRI was undertaken every 2 months for a cohort of 486 patients. The primary outcome was the total number of confirmed relapses observed during the study period. Several prespecified clinical and MRI secondary and tertiary outcomes assessed treatment efficacy on inflammation and neurodegeneration due to multiple sclerosis. Findings: The cumulative number of confirmed relapses did not differ between the two active treatment groups and the placebo group. Relative to placebo, the rate ratio for the 50 mg glatiramer acetate treated group was 0·92 (95{\%} CI 0·77-1·08, p=0·30) and for the 5 mg glatiramer acetate treated group was 0·98 (0·83-1·15, p=0·76). No drug effect was seen for any of the secondary and tertiary endpoints. The study drug was safe and well tolerated. Interpretation: 5 mg and 50 mg glatiramer acetate administered orally on a daily basis do not affect relapse rate or other clinical and MRI parameters of disease activity and burden in patients with relapsing-remitting multiple sclerosis. Treatment with oral formulations of glatiramer acetate at the doses tested cannot be recommended.",
author = "Massimo Filippi and Wolinsky, {Jerry S.} and Giancarlo Comi",
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T1 - Effects of oral glatiramer acetate on clinical and MRI-monitored disease activity in patients with relapsing multiple sclerosis

T2 - A multicentre, double-blind, randomised, placebo-controlled study

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AU - Wolinsky, Jerry S.

AU - Comi, Giancarlo

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N2 - Background: Parenterally administered glatiramer acetate reduces the frequency of relapses and the formation of active brain lesions seen with MRI in multiple sclerosis. This study assessed whether two doses of glatiramer acetate given orally could improve clinical and MRI measures of inflammation and neurodegeneration in a large cohort of patients with relapsing-remitting multiple sclerosis. Methods: 1912 patients with relapsing-remitting multiple sclerosis were screened and 1651 were randomised to receive 50 mg or 5 mg of glatiramer acetate or placebo by daily oral administration over 14 months. The intention-to-treat cohort consisted of 1644 patients who took at least one dose of study medication (50 mg glatiramer acetate [n=543], 5 mg glatiramer acetate [n=553], placebo [n=548]). After baseline investigation, clinical assessments were done every 2 months and MRI was obtained for all patients at baseline and at study exit. Additionally, MRI was undertaken every 2 months for a cohort of 486 patients. The primary outcome was the total number of confirmed relapses observed during the study period. Several prespecified clinical and MRI secondary and tertiary outcomes assessed treatment efficacy on inflammation and neurodegeneration due to multiple sclerosis. Findings: The cumulative number of confirmed relapses did not differ between the two active treatment groups and the placebo group. Relative to placebo, the rate ratio for the 50 mg glatiramer acetate treated group was 0·92 (95% CI 0·77-1·08, p=0·30) and for the 5 mg glatiramer acetate treated group was 0·98 (0·83-1·15, p=0·76). No drug effect was seen for any of the secondary and tertiary endpoints. The study drug was safe and well tolerated. Interpretation: 5 mg and 50 mg glatiramer acetate administered orally on a daily basis do not affect relapse rate or other clinical and MRI parameters of disease activity and burden in patients with relapsing-remitting multiple sclerosis. Treatment with oral formulations of glatiramer acetate at the doses tested cannot be recommended.

AB - Background: Parenterally administered glatiramer acetate reduces the frequency of relapses and the formation of active brain lesions seen with MRI in multiple sclerosis. This study assessed whether two doses of glatiramer acetate given orally could improve clinical and MRI measures of inflammation and neurodegeneration in a large cohort of patients with relapsing-remitting multiple sclerosis. Methods: 1912 patients with relapsing-remitting multiple sclerosis were screened and 1651 were randomised to receive 50 mg or 5 mg of glatiramer acetate or placebo by daily oral administration over 14 months. The intention-to-treat cohort consisted of 1644 patients who took at least one dose of study medication (50 mg glatiramer acetate [n=543], 5 mg glatiramer acetate [n=553], placebo [n=548]). After baseline investigation, clinical assessments were done every 2 months and MRI was obtained for all patients at baseline and at study exit. Additionally, MRI was undertaken every 2 months for a cohort of 486 patients. The primary outcome was the total number of confirmed relapses observed during the study period. Several prespecified clinical and MRI secondary and tertiary outcomes assessed treatment efficacy on inflammation and neurodegeneration due to multiple sclerosis. Findings: The cumulative number of confirmed relapses did not differ between the two active treatment groups and the placebo group. Relative to placebo, the rate ratio for the 50 mg glatiramer acetate treated group was 0·92 (95% CI 0·77-1·08, p=0·30) and for the 5 mg glatiramer acetate treated group was 0·98 (0·83-1·15, p=0·76). No drug effect was seen for any of the secondary and tertiary endpoints. The study drug was safe and well tolerated. Interpretation: 5 mg and 50 mg glatiramer acetate administered orally on a daily basis do not affect relapse rate or other clinical and MRI parameters of disease activity and burden in patients with relapsing-remitting multiple sclerosis. Treatment with oral formulations of glatiramer acetate at the doses tested cannot be recommended.

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