Randomized, double-blind, dose-comparison study of glatiramer acetate in relapsing-remitting MS.
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.
Cohen
J A
JA
Mellen Center for MS Treatment and Research, Cleveland Clinic Foundation, Cleveland, OH 44195, USA. cohenj@ccf.org
Rovaris
M
M
Goodman
A D
AD
Ladkani
D
D
Wynn
D
D
Filippi
M
M
D000328:Adult; D002490:Central Nervous System / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects; D055502:Secondary Prevention; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate