title: Phase III dose-comparison study of glatiramer acetate for multiple sclerosis.
abstract: OBJECTIVE
  To evaluate the safety, tolerability, and efficacy of glatiramer acetate (GA) 40 mg compared to a 20mg dose.
  
  
  METHODS
  Patients with multiple sclerosis (MS) with ≥ 1 documented relapse in 12 months prior to screening, or ≥ 2 documented relapses in 24 months prior to screening, and Expanded Disability Status Scale (EDSS) score 0 to 5.5 were enrolled. Patients were evaluated at screening, baseline, and at months 1, 2, 3, 6, 9, and 12. Primary endpoint was rate of confirmed relapses observed during 12-month study. Analysis was by intent-to-treat.
  
  
  RESULTS
  A total of 1,155 patients randomized to GA 20 mg (n = 586) or 40 mg (n = 569). The groups were well-matched at baseline on demographic, clinical, and magnetic resonance imaging (MRI) characteristics. The primary endpoint was similar in both groups (relative risk [RR] = 1.07; 95% confidence interval [CI], 0.88-1.31; p = 0.486) with mean annualized relapse rates (ARRs) of 0.33 for the 20 mg group, 0.35 for the 40 mg group, and 0.27 for patients from both groups who completed the entire 1-year treatment. A total of 77% of patients remained relapse-free in both groups. Both groups showed a reduction in mean number of gadolinium-enhancing and new T2 lesions over time with trend for faster reduction in the first trimester with the 40 mg dose compared with 20 mg dose. Both doses were well-tolerated with a safety profile similar to that observed in previous studies of 20 mg GA.
  
  
  CONCLUSIONS
  In relapsing-remitting MS patients, both the currently-approved GA 20 mg and 40 mg doses were safe and well-tolerated, with no gain in efficacy for the higher dose.
authors.affiliation: Institute of Experimental Neurology, Department of Neurology, University Vita-Salute, Scientific Institute San Raffaele, Milan, Italy. g.comi@hsr.it
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Cohen
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Arnold
authors.forename: Daniel
authors.initials: D
authors.lastname: Wynn
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000293:Adolescent; D000328:Adult; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D023381:Endpoint Determination; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D055502:Secondary Prevention; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate