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Randomized, double-blind, dose-comparison study of glatiramer acetate in relapsing–remitting MS

From the Mellen Center for MS Treatment and Research (J.A.C.), Cleveland Clinic Foundation, Cleveland, OH; Neuroimaging Research Unit (M.R., M.F.), Department of Neurology, San Raffaele Scientific Institute, Milan, Italy; Department of Neurology (A.D.G.), University of Rochester, Rochester, NY; Teva Pharmaceuticals (D.L.), Petach Tiqva, Israel; and Consultants in Neurology (D.W.), Northbrook, IL.

Address correspondence and reprint requests to Dr. Jeffrey A. Cohen, Mellen Center U-10, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail: cohenj{at}ccf.org

Objective: To evaluate the safety, tolerability, and efficacy of glatiramer acetate (GA) 40 mg daily vs the approved 20-mg formulation in relapsing–remitting multiple sclerosis.

Methods: Eligibility criteria included clinically definite multiple sclerosis, Expanded Disability Status Scale score 0 to 5.0, no previous use of GA, at least one relapse in the previous year, and 1 to 15 gadolinium-enhancing (GdE) lesions on a screening MRI. MRI was repeated at months 3, 7, 8, and 9, and neurologic examinations were performed at baseline and months 3, 6, and 9.

Results: Of 229 subjects screened, 90 were randomly assigned to GA 20 mg (n = 44) or 40 mg (n = 46). The groups were well matched at baseline for demographic, clinical, and MRI characteristics. The primary efficacy endpoint, total number of GdE lesions at months 7, 8, and 9, showed a trend favoring the 40-mg group (38% relative reduction, p = 0.0898). A difference between the two dose groups emerged as early as month 3 (52% reduction; p = 0.0051). There was a trend favoring the 40-mg group for relapse rate with benefit on proportion of relapse-free subjects (p = 0.0183) and time to first relapse (p = 0.0367). GA 40 mg was well tolerated, with an overall safety profile similar to that of 20 mg. Some features of injection site reactions and immediate postinjection reactions were more common and severe with the higher dose.

Conclusions: Glatiramer acetate (GA) 40 mg was safe and well tolerated. The overall efficacy results suggested that a 40-mg dose of GA may be more effective than the currently approved 20-mg daily dose in reducing MRI activity and clinical relapses.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the March 20 issue to find the title link for this article.

Disclosure: This study was funded by Teva Pharmaceuticals, of which Dr. Ladkani is an employee. The other authors have served as paid consultants or speakers for Teva Pharmaceuticals (less than $10,000 per year) and have received research support to their institutions, but none has a personal financial investment, ownership, equity, or other financial holdings. Preliminary results were presented at the annual meetings of the American Academy of Neurology in April 2006 in San Diego, CA, and the European Committee for Treatment and Research in Multiple Sclerosis in September 2006 in Madrid, Spain.

Received June 7, 2006. Accepted in final form November 28, 2006.