Multiple sclerosisWednesday, May 31, 2006, 08:30 - 10:00
Results of a randomised, double-blind, parallel-group study assessing safety and efficacy of 40 mg vs. 20 mg of glatiramer acetate on MRI-measured disease activity in relapsing-remitting multiple sclerosisM. Rovaris, J. Cohen, A. Goodman, G. Comi, M. Filippi on behalf of the 9006 Study Group
Objectives: Twenty mg GA (CopaxoneŽ) is an approved therapy for relapsing-remitting multiple sclerosis (RRMS). Its safety and efficacy are supported by three pivotal trials and over a decade of experience. We evaluated safety and efficacy of 40 mg of glatiramer acetate (GA) given subcutaneously every day for 9 months vs. those of the approved drug formulation (20 mg) in RRMS patients.
Design/Methods: Key eligibility criteria included clinically definite MS with a relapse in the prior year, EDSS score 0-5.0, no prior use of GA and at least one gadolinium (Gd)-enhancing lesion on a screening MRI. Subjects underwent MRI scans at baseline and at months 3, 7, 8 and 9. Neurological examinations were performed at baseline and at months 3, 6 and 9. Suspected on-trial relapses were confirmed at an unscheduled visit. The primary efficacy endpoint was the total number of Gd-enhancing lesions at months 7, 8 and 9. The difference between the two treatment arms was assessed using a Poisson regression model accounting for study site and baseline Gd-enhancing lesion counts.
Results: Of 229 screened subjects 90 were eligible. The two treatment groups were well-matched for age, disease duration, EDSS, pre-study annual relapse rate and number of Gd-enhancing lesions at baseline. A 38% greater reduction (relative risk = 0.62, 95% CI = 0.36-1.08, p=0.0898) in favour of 40 mg vs. 20 mg in the mean cumulative number of Gd-enhancing lesions at months 7, 8 and 9 was observed (mean per scan = 0.79 vs. 1.32 lesions for the 40 and 20 mg groups, respectively). This difference emerged as early as month 3 (mean number of lesions was 1.33 and 2.61 for the 40 and 20 mg groups; p=0.005). When compared to baseline, the risk of having enhancement in the 40 mg group at months 7, 8 and 9 was reduced by 75% (relative risk = 0.25, 95% CI = 0.15-0.40, p<0.0001) and by 65% in the 20 mg group (relative risk = 0.35, 95% CI = 0.24-0.53, p<0.0001). Mean relapse rate during the study period was 0.34 in the 40 mg and 0.57 in the 20 mg group. In the 20% of subjects who experienced a relapse during the trial, time to the first relapse was delayed from 80 days in the 20 mg group to 213 days in the 40 mg group (p=0.0367). GA 40 mg was well-tolerated with a safety profile similar to the 20 mg dose.
Conclusions: Over a nine-month period of observation, GA 40 mg is safe, well-tolerated and more effective than the currently approved 20 mg dose in reducing MRI activity and relapse rate in patients with RRMS.