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

Mult Scler. 2017 May;23(6):818-829. doi: 10.1177/1352458516664033. Epub 2016 Aug 8.

Abstract

Background: 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.

Objective: To evaluate the effects of early start (ES) and delayed start (DS) of GA40 over 3 years.

Methods: 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.

Results: 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.

Conclusion: GA40 conferred treatment benefit over 3 years: sustained low ARR and lesion activity and favorable safety.

Trial registration: ClinicalTrials.gov NCT01067521.

Keywords: Glatiramer acetate; annualized relapse rate; low-frequency regimen; relapsing–remitting multiple sclerosis; safety.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Disease Progression
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Glatiramer Acetate* / administration & dosage
  • Glatiramer Acetate* / adverse effects
  • Glatiramer Acetate* / pharmacology
  • Humans
  • Immunosuppressive Agents* / administration & dosage
  • Immunosuppressive Agents* / adverse effects
  • Immunosuppressive Agents* / pharmacology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / diagnostic imaging*
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / physiopathology
  • Outcome Assessment, Health Care*
  • Recurrence

Substances

  • Immunosuppressive Agents
  • Glatiramer Acetate

Associated data

  • ClinicalTrials.gov/NCT01067521