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 ϭ 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 ϭ 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.

Bayer HealthCare Pharmaceuticals.

Based on scientific literature and interviews with clinicians and patients, we developed a quality of life instrument for use with people with MS called the Functional Assessment of Multiple Sclerosis (FAMS). The initial item pool consisted of 88 questions: 28 from the general version of the Functional Assessment of Cancer Therapy quality of life instrument, plus 60 generated by patients, providers, and literature review. The validation samples comprised a mail survey cohort (N = 377) and a clinical cohort (N = 56). Both cohorts provides evidence for internal consistency of the derived subscales, test-retest reliability, content validity, concurrent validity, and construct validity. Principal components and Rasch measurement model analyses were applied sequentially to survey sample data, reducing test length to 44 questions, divided into six subscales: mobility, symptoms, emotional well-being (depression), general contentment, thinking/fatigue, and family/social well-being. Fifteen initially rejected questions were added back as miscellaneous (unscored) questions for their potential clinical and empirical value. The mobility subscale was strongly predictive of the Kurtzke Extended Disability Status Scale and the Scripps Neurologic Rating Scales. The other five subscales were not, indicating they measure aspects of patient quality of life not captured by the neurologic exam. The final 59-item English language instrument (FAMS version 2) is available for inclusion in clinical trials and clinical practice.

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