Effect of switching from glatiramer acetate 20 mg/daily to glatiramer acetate 40 mg three times a week on gray and white matter pathology in subjects with relapsing multiple sclerosis: A longitudinal DTI study

J Neurol Sci. 2018 Apr 15;387:152-156. doi: 10.1016/j.jns.2018.02.023. Epub 2018 Feb 10.

Abstract

Background: Glatiramer acetate (GA) 40 mg × 3/weekly was approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). While the beneficial effect of GA 20 mg/daily in MS patients on non-conventional MRI measures has been demonstrated, the effect of GA 40 mg × 3/weekly at the microstructural tissue level has yet to be explored.

Objective: To investigate the effect of switching from GA 20 mg/daily to GA 40 mg × 3/weekly on the evolution of microstructural changes in the thalamus and normal appearing white matter (NAWM), using diffusion tensor imaging (DTI).

Methods: In this observational, longitudinal, cross-over, 34-month MRI study, we recruited 150 RRMS patients that underwent MRI 12-18 months before switching (pre-index), during the switch (index) and 12-18 months after switching (post-index) from GA 20 mg/daily to GA 40 mg × 3/weekly. Regional DTI metrics and tract-based spatial statistics (TBSS) analyses were performed. Mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) and fractional anisotropy (FA) were measured in thalamus and NAWM.

Results: Regional DTI measures, measures of whole brain, white and gray matter, and thalamus volumes, as well as lesion volume, showed no significant changes. However, the voxel-wise TBSS analysis showed increased FA both in the NAWM and thalamus, as well as increased MD and AD in NAWM, and decreased RD in NAWM (p < .05). Areas of increased FA and MD as well as decreased RD in the NAWM, and increased AD both in the NAWM and thalamus were detected between index to post-index (p < .05).

Conclusions: This study confirms a comparable effect of GA 40 mg × 3/weekly to GA 20 mg/daily on DTI measures over 34 months.

Trial registration: ClinicalTrials.gov NCT02308670.

Keywords: DTI; GM; Glatiramer acetate; MRI; Multiple sclerosis; Tract based spatial statistics; WM.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Analysis of Variance
  • Anisotropy
  • Cross-Over Studies
  • Diffusion Magnetic Resonance Imaging
  • Disability Evaluation
  • Dose-Response Relationship, Drug
  • Female
  • Glatiramer Acetate / therapeutic use*
  • Gray Matter / diagnostic imaging*
  • Gray Matter / drug effects*
  • Humans
  • Image Processing, Computer-Assisted
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / diagnostic imaging*
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • White Matter / diagnostic imaging*
  • White Matter / drug effects*
  • Young Adult

Substances

  • Glatiramer Acetate

Associated data

  • ClinicalTrials.gov/NCT02308670