Effects of glatiramer acetate on relapse rate and accumulated disability in multiple sclerosis: meta-analysis of three double-blind, randomized, placebo-controlled clinical trials.
Three randomized, double-blind, placebo-controlled trials have shown that glatiramer acetate (GA) is effective in reducing relapse rate in patients with relapsing-remitting (RR) multiple sclerosis (MS). Using raw data pooled from 540 patients, we performed a meta-analysis of these three trials, to investigate whether the extent of GA efficacy varies according to disease-related variables at study entry. Three regression models were developed to assess the efficacy of GA on the annualized relapse rate (primary outcome measure), on the total number of on-trial relapses and on the time to first relapse. We also explored the efficacy of GA on accumulated disability and the potential role of baseline clinical variables as predictors of relapse-rate variables and treatment efficacy. The mean adjusted annualized relapse rate on study was 1.14 in the pooled placebo-treated subjects and 0.82 in the pooled GA group (P = 0.004), indicating an average reduction in annualized relapse rate of 28%. About a one third reduction of the total number of on-trial relapses was also observed in patients receiving GA (P < 0.0001), who had a median time to the first relapse of 322 days versus a median time to the first relapse of 219 days seen in those receiving placebo (P = 0.01). A beneficial effect on accumulated disability was also found (risk ratio of 0.6; 95%; CI = 0.4-0.9; P = 0.02). The drug assignment (P = 0.004), baseline EDSS score (P = 0.02) and number of relapses during the two years prior to study entry (P = 0.002) were significant predictors of on-trial annualized relapse rate. No other demographic or clinical variable at baseline significantly influenced the treatment effect. This meta-analysis reaffirms the effectiveness of GA in reducing relapse rate and disability accumulation in RRMS, at a magnitude comparable to that of other available immunomodulating treatments. It also suggests that GA efficacy is not significantly influenced by the patients' clinical characteristics at the time of treatment initiation.
Martinelli Boneschi
Filippo
F
Department of Neuroscience, Scientific Institute, University H San Raffaele, Milan, Italy.
Rovaris
Marco
M
Johnson
Kenneth P
KP
Miller
Aaron
A
Wolinsky
Jerry S
JS
Ladkani
David
D
Shifroni
Galia
G
Comi
Giancarlo
G
Filippi
Massimo
M
D004185:Disability Evaluation; D004311:Double-Blind Method; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D010455:Peptides / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate