Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: Results of a phase III multicenter, double-blind placebo-controlled trial

Copolymer 1 Multiple Sclerosis Study Group

Research output: Contribution to journalArticle

1662 Citations (Scopus)

Abstract

We studied copolymer 1 (Copaxone) in a multicenter (11–university) phase III trial of patients with relapsing–remitting multiple sclerosis (MS). Two hundred fifty–one patients were randomized to receive copolymer 1 (n = 125) or placebo (n = 126) at a dosage of 20 mg by daily subcutaneous injection for 2 years. The primary end point was a difference in the MS relapse rate. The final 2–year relapse rate was 1.19 ± 0.13 for patients receiving copolymer 1 and 1.68 ± 0.13 for those receiving placebo, a 29% reduction in favor of copolymer 1 (p = 0.007) (annualized rates = 0.59 for copolymer 1 and 0.84 for placebo). Trends in the proportion of relapse–free patients and median time to first relapse favored copolymer 1. Disability was measured by the Expanded Disability Status Scale (EDSS), using a two–neurologist (examining and treating) protocol. When the proportion of patients who improved, were unchanged, or worsened by ≥1 EDSS step from baseline to conclusion (2 years) was evaluated, significantly more patients receiving copolymer 1 were found to have improved and more receiving placebo worsened (p = 0.037). Patient withdrawals were 19 (15.2%) from the copolymer 1 group and 17 (13.5%) from the placebo group at approximately the same intervals. The treatment was well tolerated. The most common adverse experience was an injection–site reaction. Rarely, a transient self–limited systemic reaction followed the injection in 15.2% of those receiving copolymer 1 and 3.2% of those receiving placebo. This reaction was characterized by flushing or chest tightness with palpitations, anxiety, or dyspnea and commonly lasted for 30 seconds to 30 minutes. This rigorous study confirmed the findings of a previous pilot trial and demonstrated that copolymer 1 treatment can significantly and beneficially alter the course of relapsing–remitting MS in a well–tolerated fashion.

Original languageEnglish (US)
Pages (from-to)1268-1276
Number of pages9
JournalNeurology
Volume45
Issue number7
StatePublished - 1995
Externally publishedYes

Fingerprint

Relapsing-Remitting Multiple Sclerosis
Placebos
Recurrence
Multiple Sclerosis
Subcutaneous Injections
Controlled
Placebo
Relapse
Dyspnea
Thorax
Anxiety
Injections
Therapeutics

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology
  • Neuroscience(all)

Cite this

Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis : Results of a phase III multicenter, double-blind placebo-controlled trial. / Copolymer 1 Multiple Sclerosis Study Group.

In: Neurology, Vol. 45, No. 7, 1995, p. 1268-1276.

Research output: Contribution to journalArticle

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title = "Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: Results of a phase III multicenter, double-blind placebo-controlled trial",
abstract = "We studied copolymer 1 (Copaxone) in a multicenter (11–university) phase III trial of patients with relapsing–remitting multiple sclerosis (MS). Two hundred fifty–one patients were randomized to receive copolymer 1 (n = 125) or placebo (n = 126) at a dosage of 20 mg by daily subcutaneous injection for 2 years. The primary end point was a difference in the MS relapse rate. The final 2–year relapse rate was 1.19 ± 0.13 for patients receiving copolymer 1 and 1.68 ± 0.13 for those receiving placebo, a 29{\%} reduction in favor of copolymer 1 (p = 0.007) (annualized rates = 0.59 for copolymer 1 and 0.84 for placebo). Trends in the proportion of relapse–free patients and median time to first relapse favored copolymer 1. Disability was measured by the Expanded Disability Status Scale (EDSS), using a two–neurologist (examining and treating) protocol. When the proportion of patients who improved, were unchanged, or worsened by ≥1 EDSS step from baseline to conclusion (2 years) was evaluated, significantly more patients receiving copolymer 1 were found to have improved and more receiving placebo worsened (p = 0.037). Patient withdrawals were 19 (15.2{\%}) from the copolymer 1 group and 17 (13.5{\%}) from the placebo group at approximately the same intervals. The treatment was well tolerated. The most common adverse experience was an injection–site reaction. Rarely, a transient self–limited systemic reaction followed the injection in 15.2{\%} of those receiving copolymer 1 and 3.2{\%} of those receiving placebo. This reaction was characterized by flushing or chest tightness with palpitations, anxiety, or dyspnea and commonly lasted for 30 seconds to 30 minutes. This rigorous study confirmed the findings of a previous pilot trial and demonstrated that copolymer 1 treatment can significantly and beneficially alter the course of relapsing–remitting MS in a well–tolerated fashion.",
author = "{Copolymer 1 Multiple Sclerosis Study Group} and Johnson, {Kenneth P.} and Brooks, {B. R.} and Cohen, {J. A.} and Ford, {C. C.} and J. Goldstein and Lisak, {R. P.} and Myers, {L. W.} and Panitch, {H. S.} and Rose, {J. W.} and Schiffer, {R. B.} and T. Vollmer and Weiner, {L. P.} and Wolinsky, {J. S.} and Bird, {Shawn J.} and Kolson, {Dennis L.} and Francisco Gonzalez–scarano and Daniel Brennan and Dorothea Pfohl and Mandler, {Raul N.} and Rosenberg, {Gary A.} and Carol Jeffrey and Barger, {Geoffrey R.} and Balbir Gandhi and Moore, {Patricia M.} and Rogers, {Lisa R.} and Deena Lisak and Lissa Smith and Ellison, {George W.} and Baumhefner, {Robert W.} and Craig, {Sharon L.} and Jalbut, {Suhayl S.} and Eleanor Katz and Conway, {Kathleen L S} and Burns, {James B.} and Connie Shiba and Giang, {Daniel W.} and Petrie, {Mary D.} and Guarnaccia, {Joseph B.} and Susan Anderson and {Mc Keon}, Anne and Micheline McCarthy and Thomas, {Azreena B.} and Vriesendorp, {Francine J.} and Austin, {Sara G.} and Lindsey, {John W.} and Mazen Dimachkie and Emily Cerreta and Norman Kachuck and {Mc Carthy}, {Kathleen A.} and John Fleming",
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TY - JOUR

T1 - Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis

T2 - Results of a phase III multicenter, double-blind placebo-controlled trial

AU - Copolymer 1 Multiple Sclerosis Study Group

AU - Johnson, Kenneth P.

AU - Brooks, B. R.

AU - Cohen, J. A.

AU - Ford, C. C.

AU - Goldstein, J.

AU - Lisak, R. P.

AU - Myers, L. W.

AU - Panitch, H. S.

AU - Rose, J. W.

AU - Schiffer, R. B.

AU - Vollmer, T.

AU - Weiner, L. P.

AU - Wolinsky, J. S.

AU - Bird, Shawn J.

AU - Kolson, Dennis L.

AU - Gonzalez–scarano, Francisco

AU - Brennan, Daniel

AU - Pfohl, Dorothea

AU - Mandler, Raul N.

AU - Rosenberg, Gary A.

AU - Jeffrey, Carol

AU - Barger, Geoffrey R.

AU - Gandhi, Balbir

AU - Moore, Patricia M.

AU - Rogers, Lisa R.

AU - Lisak, Deena

AU - Smith, Lissa

AU - Ellison, George W.

AU - Baumhefner, Robert W.

AU - Craig, Sharon L.

AU - Jalbut, Suhayl S.

AU - Katz, Eleanor

AU - Conway, Kathleen L S

AU - Burns, James B.

AU - Shiba, Connie

AU - Giang, Daniel W.

AU - Petrie, Mary D.

AU - Guarnaccia, Joseph B.

AU - Anderson, Susan

AU - Mc Keon, Anne

AU - McCarthy, Micheline

AU - Thomas, Azreena B.

AU - Vriesendorp, Francine J.

AU - Austin, Sara G.

AU - Lindsey, John W.

AU - Dimachkie, Mazen

AU - Cerreta, Emily

AU - Kachuck, Norman

AU - Mc Carthy, Kathleen A.

AU - Fleming, John

PY - 1995

Y1 - 1995

N2 - We studied copolymer 1 (Copaxone) in a multicenter (11–university) phase III trial of patients with relapsing–remitting multiple sclerosis (MS). Two hundred fifty–one patients were randomized to receive copolymer 1 (n = 125) or placebo (n = 126) at a dosage of 20 mg by daily subcutaneous injection for 2 years. The primary end point was a difference in the MS relapse rate. The final 2–year relapse rate was 1.19 ± 0.13 for patients receiving copolymer 1 and 1.68 ± 0.13 for those receiving placebo, a 29% reduction in favor of copolymer 1 (p = 0.007) (annualized rates = 0.59 for copolymer 1 and 0.84 for placebo). Trends in the proportion of relapse–free patients and median time to first relapse favored copolymer 1. Disability was measured by the Expanded Disability Status Scale (EDSS), using a two–neurologist (examining and treating) protocol. When the proportion of patients who improved, were unchanged, or worsened by ≥1 EDSS step from baseline to conclusion (2 years) was evaluated, significantly more patients receiving copolymer 1 were found to have improved and more receiving placebo worsened (p = 0.037). Patient withdrawals were 19 (15.2%) from the copolymer 1 group and 17 (13.5%) from the placebo group at approximately the same intervals. The treatment was well tolerated. The most common adverse experience was an injection–site reaction. Rarely, a transient self–limited systemic reaction followed the injection in 15.2% of those receiving copolymer 1 and 3.2% of those receiving placebo. This reaction was characterized by flushing or chest tightness with palpitations, anxiety, or dyspnea and commonly lasted for 30 seconds to 30 minutes. This rigorous study confirmed the findings of a previous pilot trial and demonstrated that copolymer 1 treatment can significantly and beneficially alter the course of relapsing–remitting MS in a well–tolerated fashion.

AB - We studied copolymer 1 (Copaxone) in a multicenter (11–university) phase III trial of patients with relapsing–remitting multiple sclerosis (MS). Two hundred fifty–one patients were randomized to receive copolymer 1 (n = 125) or placebo (n = 126) at a dosage of 20 mg by daily subcutaneous injection for 2 years. The primary end point was a difference in the MS relapse rate. The final 2–year relapse rate was 1.19 ± 0.13 for patients receiving copolymer 1 and 1.68 ± 0.13 for those receiving placebo, a 29% reduction in favor of copolymer 1 (p = 0.007) (annualized rates = 0.59 for copolymer 1 and 0.84 for placebo). Trends in the proportion of relapse–free patients and median time to first relapse favored copolymer 1. Disability was measured by the Expanded Disability Status Scale (EDSS), using a two–neurologist (examining and treating) protocol. When the proportion of patients who improved, were unchanged, or worsened by ≥1 EDSS step from baseline to conclusion (2 years) was evaluated, significantly more patients receiving copolymer 1 were found to have improved and more receiving placebo worsened (p = 0.037). Patient withdrawals were 19 (15.2%) from the copolymer 1 group and 17 (13.5%) from the placebo group at approximately the same intervals. The treatment was well tolerated. The most common adverse experience was an injection–site reaction. Rarely, a transient self–limited systemic reaction followed the injection in 15.2% of those receiving copolymer 1 and 3.2% of those receiving placebo. This reaction was characterized by flushing or chest tightness with palpitations, anxiety, or dyspnea and commonly lasted for 30 seconds to 30 minutes. This rigorous study confirmed the findings of a previous pilot trial and demonstrated that copolymer 1 treatment can significantly and beneficially alter the course of relapsing–remitting MS in a well–tolerated fashion.

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