Glatiramer acetate (Copaxone): comparison of continuous versus delayed therapy in a six-year organized multiple sclerosis trial.
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The aim of this study was to assess the long-term safety and efficacy of glatiramer acetate (GA) for patients with multiple sclerosis (MS) who received active treatment versus those on placebo for approximately 30 months (24-35 months) before receiving GA during a six-year organized, prospective open label study. Entry required two relapses in the previous two years and an Expanded Disability Status Scale (EDSS) score of 0-5. Patients (251) were equally randomized to daily subcutaneous GA, 20 mg, or to placebo. After approximately 30 months, 208 patients continued in an open label study: 101 continued on GA and 107 switched from placebo to active drug. Groups were well matched at randomization and entry to the open label study. Patients always on GA showed a steady decline in relapses: a mean of 1.5 per year at entry, a mean of 0.42 over the entire six years (95% CI = 0.34-0.51), a 72% reduction (P = 0.0001). They averaged a relapse every four + years (yearly rate 0.23 in year six) and 26/101 remain relapse free. Patients did less well if on placebo for 30 months, but relapses then declined, and by year six the rates were similar. Of patients always on GA, 69% showed neurological improvement of > or = 1 EDSS steps or remained stable compared with 57% if GA treatment was delayed. Of relapse-free patients always on GA over six years, only three of 26 (11%) were worse by > or = 1 EDSS steps, whereas nine of 21 (43%) in the placebo/active group were worse (P < 0.03). Disability, measured every six months, showed that the group of patients always on GA was relatively stable over the six years, while the group who received placebo for the first two-and-a-half years did significantly less well. Daily injections of GA were well tolerated. This longest ever organized MS treatment trial shows that delaying therapy with GA increases the risk of neurologic disability, reinforcing the rationale for using GA as a first-line treatment early in the course of relapsing-remitting MS.