Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial.

Abstract

OBJECTIVE:

To determine whether glatiramer acetate (GA) slows accumulation of disability in primary progressive multiple sclerosis.

METHODS:

A total of 943 patients with primary progressive multiple sclerosis were randomized to GA or placebo (PBO) in this 3-year, double-blind trial. The primary end point was an intention-to-treat analysis of time to 1- (entry expanded disability status scale, 3.0-5.0) or 0.5-point expanded disability status scale change (entry expanded disability status scale, 5.5-6.5) sustained for 3 months. The trial was stopped after an interim analysis by an independent data safety monitoring board indicated no discernible treatment effect on the primary outcome. Intention-to-treat analyses of disability and magnetic resonance imaging end points were performed.

RESULTS:

There was a nonsignificant delay in time to sustained accumulated disability in GA- versus PBO-treated patients (hazard ratio, 0.87 [95% confidence interval, 0.71-1.07]; p = 0.1753), with significant decreases in enhancing lesions in year 1 and smaller increases in T2 lesion volumes in years 2 and 3 versus PBO. Post hoc analysis showed that survival curves for GA-treated male patients diverged early from PBO-treated male subjects (hazard ratio, 0.71 [95% confidence interval, 0.53-0.95]; p = 0.0193).

INTERPRETATION:

The trial failed to demonstrate a treatment effect of GA on primary progressive multiple sclerosis. Both the unanticipated low event rate and premature discontinuation of study medication decreased the power to detect a treatment effect. Post hoc analysis suggests GA may have slowed clinical progression in male patients who showed more rapid progression when untreated.

• Authors: Jerry S Wolinsky, Ponnada A Narayana, Paul O'Connor, Patricia K Coyle, Corey Ford, Kenneth Johnson, Aaron Miller, Lillian Pardo, Shaul Kadosh, David Ladkani, PROMiSe Trial Study Group
• Journal: Annals of neurology (Ann Neurol) Vol. 61 Issue 1 Pg. 14-24 (Jan 2007) ISSN: 0364-5134 [Print] United States
• PMID: 17262850 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Immunosuppressive Agents
• Peptides
• Glatiramer Acetate

Topics

• Adult
• Disability Evaluation
• Double-Blind Method
• Female
• Follow-Up Studies
• Glatiramer Acetate
• Humans
• Immunosuppressive Agents (therapeutic use)
• International Cooperation
• Male
• Middle Aged
• Multiple Sclerosis, Chronic Progressive (drug therapy)
• Peptides (therapeutic use)
• Proportional Hazards Models
• Retrospective Studies
• Severity of Illness Index
• Sex Factors