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


CONCLUSIONS
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.
Wolinsky
Jerry S
JS
Department of Neurology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA. jerry.s.wolinsky@uth.tmc.edu
Narayana
Ponnada A
PA
O'Connor
Paul
P
Coyle
Patricia K
PK
Ford
Corey
C
Johnson
Kenneth
K
Miller
Aaron
A
Pardo
Lillian
L
Kadosh
Shaul
S
Ladkani
David
D
D000328:Adult; D004185:Disability Evaluation; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy*; D010455:Peptides / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012720:Severity of Illness Index; D012737:Sex Factors
D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate