title: GLACIER: An open-label, randomized, multicenter study to assess the safety and tolerability of glatiramer acetate 40 mg three-times weekly versus 20 mg daily in patients with relapsing-remitting multiple sclerosis.
abstract: BACKGROUND
  The efficacy and safety of glatiramer acetate (GA) 20 mg/mL once-daily subcutaneous injections (GA20) in relapsing-remitting multiple sclerosis (RRMS) is well-established. However, injection-related adverse events (IRAEs) may impede treatment adherence and tolerability. GA 40 mg/mL three-times weekly (GA40) also has a favorable efficacy and safety profile.
  
  
  OBJECTIVE
  To evaluate the safety, tolerability, and patient experience when converting from GA20 to GA40.
  GLACIER was an open-label, randomized, parallel-group trial conducted at 31 sites in the US between June 2013 and December 2013. Stable RRMS patients on GA20 were randomized in a 1:1 ratio to continue with GA20 or convert to GA40. The adjusted mean annualized rate of IRAEs was the primary endpoint for this study. Additionally, the severity of IRAEs, rate of injection-site reactions (ISRs), and patient-reported MS impact and treatment satisfaction were compared for the two treatment groups over the 4-month core study.
  
  
  RESULTS
  A total of 209 patients were randomized to convert to GA40 (n=108) or continue with GA20 (n=101). The adjusted mean annualized rate of IRAEs was reduced by 50% with GA40 (35.3 events per year; n=108) versus GA20 (70.4 events per year; n=101) (risk ratio (RR)=0.50; 95% confidence interval [CI]=0.34-0.74; p=0.0006). There was a 60% reduction in the rate of moderate/severe events (GA40 (n=108): 0.9 events per year versus GA20 (n=101): 2.2 events per year; RR=0.40; p=0.0021). Perception of treatment convenience improved for GA40-treated patients soon after converting and was sustained.
  
  
  CONCLUSIONS
  The GLACIER study demonstrates a favorable IRAE and convenience profile of GA40 for RRMS patients.
  
  
  BACKGROUND
  NCT01874145 available at clinicaltrial.gov.
authors.affiliation: University of Texas Health Science Center at Houston, Houston, TX, USA. Electronic address: Jerry.S.Wolinsky@uth.tmc.edu.
authors.forename: Jerry S
authors.initials: JS
authors.lastname: Wolinsky
authors.affiliation: Mecklenburg Neurological Associates, Charlotte, NC, USA.
authors.forename: T Erik
authors.initials: TE
authors.lastname: Borresen
authors.affiliation: Advanced Neurological Specialists, Great Falls, MT, USA.
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dietrich
authors.affiliation: Consultants in Neurology, Northbrook, IL, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wynn
authors.affiliation: Teva Pharmaceuticals, Netanya, Israel.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Sidi
authors.affiliation: Global Clinical Development, Teva Pharmaceuticals, Frazer, PA, USA.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Steinerman
authors.affiliation: Global Clinical Development, Teva Pharmaceuticals, Frazer, PA, USA; Heinrich-Heine Universität Düsseldorf, Düsseldorf, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Knappertz
authors.affiliation: Teva Pharmaceuticals, Cleveland, OH, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Kolodny
mesh_terms: D015331:Cohort Studies; D004185:Disability Evaluation; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D000068717:Glatiramer Acetate / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007279:Injections, Subcutaneous / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D017060:Patient Satisfaction; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014481:United States
chemical_list: D007166:Immunosuppressive Agents; D000068717:Glatiramer Acetate
keywords: Convenience; Dose regimen; Glatiramer acetate; Patient adherence; Relapsing-remitting multiple sclerosis; Safety