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.
RCT Entities:
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: M Mateo Paz Soldán; Martina Novotna; Nuhad Abou Zeid; Nilufer Kale; Melih Tutuncu; Daniel J Crusan; Elizabeth J Atkinson; Aksel Siva; B Mark Keegan; Istvan Pirko; Sean J Pittock; Claudia F Lucchinetti; Brian G Weinshenker; Moses Rodriguez; Orhun H Kantarci Journal: Neurology Date: 2014-11-14 Impact factor: 9.910
Authors: Stuart D Cook; Suhayl Dhib-Jalbut; Peter Dowling; Luca Durelli; Corey Ford; Gavin Giovannoni; June Halper; Colleen Harris; Joseph Herbert; David Li; John A Lincoln; Robert Lisak; Fred D Lublin; Claudia F Lucchinetti; Wayne Moore; Robert T Naismith; Carlos Oehninger; Jack Simon; Maria Pia Sormani Journal: Int J MS Care Date: 2012
Authors: Martin Duddy; Aiden Haghikia; Eleonora Cocco; Christian Eggers; Jelena Drulovic; Olga Carmona; Helene Zéphir; Ralf Gold Journal: J Neurol Date: 2011-03-25 Impact factor: 4.849