Sustained clinical benefits of glatiramer acetate in relapsing multiple sclerosis patients observed for 6 years

Abstract

In a randomized, placebo-controlled, double-blind study, glatiramer acetate (Copaxone) reduced the relapse rate and slowed accumulation of disability for patients with relapsing - remitting multiple sclerosis. Of the original 251 patients randomized to receive glatiramer acetate or placebo, 208 chose to continue in an open-label study with all patients receiving active drug. The majority of the original double-blind cohort continues to receive glatiramer acetate by daily subcutaneous injection and are evaluated at 6-month intervals and during suspected relapse. The data reported here are from approximately 6 years of organized evaluation, including the double-blind phase of up to 35 months and the open-label phase of over 36 months. Daily subcutaneous injections of 20 mg glatiramer acetate were well tolerated. The mean annual relapse rate of the patients who received glatiramer acetate since randomization and continued into the open-label study was 0.42 (95% confidence interval (CI), CI=0.34 - 0.51). The rate per year has continued to drop and for the sixth year is 0.23. Of the group who have received glatiramer acetate without interruption for 5 or more years, 69.3% were neurologically unchanged or have improved from baseline by at least one step on the Expanded Disability Status Scale (EDSS). Patients who left the open-label phase were surveyed by questionnaire. The majority responded, providing information about their current status and reasons for dropping out. This study demonstrates the sustained efficacy of glatiramer acetate in reducing the relapse rate and in slowing the accumulation of disability in patients with relapsing forms of multiple sclerosis. Multiple Sclerosis (2000) 6 255 - 266

Induction of Apoptosis of CD4+ T Cells by Immunomodulatory Therapy of Multiple Sclerosis with Glatiramer Acetate

“…In MS therapy, several clinical trials have demonstrated the efficacy of glatiramer acetate (GA; copolymer-1; Copaxone ® ) in reducing the relapse rate and the magnetic resonance imaging (MRI)-defined disease activity in patients with a relapsing-remitting (RR) course [5, 6, 7]. Current concepts propose that GA, initially developed to mimic a major component of the myelin sheath, myelin basic protein, leads to partial activation and tolerance induction of myelin-specific T cells, and/or an induction of GA-reactive T helper 2 (Th2)-type regulatory cells [8].…”

Amelioration of proteolipid protein 139–151-induced encephalomyelitis in SJL mice by modified amino acid copolymers and their mechanisms

“…Cop1 was originally designed to induce EAE, but instead was found to be effective in suppressing EAE (20)(21)(22)(23) and is in current use in the treatment of relapsing-remitting forms of MS (24)(25)(26). A recent clinical study demonstrated its sustained efficacy in MS patients over a period of 6 years (27). Nevertheless, Cop1 only has a modest effect on the course of the disease.…”

Escalating immunotherapy of multiple sclerosis

“…1. There are hints from the six years observation period of the Copaxone study in the U. S. indicating that starting treatment at an earlier time may be associated with a reduced risk for disease progression as measured by the EDSS [23]. Similar results were also extracted from data derived from the pivotal studies with interferon-beta preparations in RRMS.…”

“…Open label, follow-up examinations revealed a continuous treatment effect if compared to the natural disease course [23]. The 9-month results of a placebocontrolled study on the influence of Copaxone® on the subclinical disease activity as measured by cranial MRI were recently published [8].…”