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

Background Glatiramer acetate (GA) 40 mg x 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 x 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 x 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 x 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 x 3/weekly to GA 20 mg/daily on DTI measures over 34 months.