title: Efficacy and safety of a three-times-weekly dosing regimen of glatiramer acetate in relapsing-remitting multiple sclerosis patients: 3-year results of the Glatiramer Acetate Low-Frequency Administration open-label extension study.
abstract: The 1-year placebo-controlled (PC) phase of the Glatiramer Acetate Low-Frequency Administration (GALA) study showed that glatiramer acetate 40 mg/mL three times weekly (GA40) significantly reduced annualized relapse rate (ARR) and magnetic resonance imaging (MRI) activity in patients with relapsing-remitting multiple sclerosis. Patients completing the PC phase were invited to an open-label (OL) extension.
  
  
  
  To evaluate the effects of early start (ES) and delayed start (DS) of GA40 over 3 years.
  
  
  
  A total of 97.2% of patients completing the PC phase received GA40 in the OL extension. ES ( n = 943) patients received GA40 throughout; DS ( n = 461) patients received placebo during the PC phase and GA40 during the OL phase. Relapse, MRI, disease progression, and safety were evaluated.
  
  
  
  A total of 1041 patients completed 3 years of follow-up. During the OL phase, ES and DS patients showed comparable ARRs (0.20-0.22) and similar numbers of gadolinium-enhancing T1 ( p = 0.49) and new or enlarging T2 lesions ( p = 0.51) at Year 3. ES patients showed significantly smaller changes in gray matter volume than DS patients from Months 12 to 36 (mean difference, 0.371%; p = 0.015), with similar trend in whole-brain volume ( p = 0.080). Adverse events were mild, consistent with the well-established glatiramer acetate (GA) safety profile.
  
  
  
  GA40 conferred treatment benefit over 3 years: sustained low ARR and lesion activity and favorable safety.
authors: The Sastry Foundation Advanced Imaging Laboratory & Multiple Sclerosis Center, Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA.
authors: Omar
authors: O
authors: Khan
authors: Department of Neurology, Bamberg Academic Hospital, University of Erlangen, Bamberg, Germany.
authors: Peter
authors: P
authors: Rieckmann
authors: Department of Neurology, Neurosurgery and Medical Genetic of the Pirogov's Russian National Research Medical University and MS Clinic at the Usupov's Hospital, Moscow, Russia.
authors: Alexey
authors: A
authors: Boyko
authors: Department of Neurology, Medical University of Łódź, Łódź, Poland.
authors: Krzysztof
authors: K
authors: Selmaj
authors: Teva Pharmaceutical Industries, Netanya, Israel.
authors: Natalia
authors: N
authors: Ashtamker
authors: Teva Pharmaceuticals, Frazer, PA, USA.
authors: Mat D
authors: MD
authors: Davis
authors: Teva Pharmaceuticals, Cleveland, OH, USA.
authors: Scott
authors: S
authors: Kolodny
authors: Department of Neurology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
authors: Robert
authors: R
authors: Zivadinov
mesh_terms: D000328:Adult; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D000068717:Glatiramer Acetate / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000503:physiopathology; D017063:Outcome Assessment, Health Care; D012008:Recurrence
chemical_list: D007166:Immunosuppressive Agents; D000068717:Glatiramer Acetate
keywords: Glatiramer acetate; annualized relapse rate; low-frequency regimen; relapsing–remitting multiple sclerosis; safety