Comparative Longitudinal Analysis of Fingolimod Versus Glatitamer Acetate in Myelin Repair and Tissue Integrity: A 24-Months Follow-up Study.

Background: The relative effectiveness of disease modifying therapies (DMTs) on myelin repair, structural tissue integrity and axonal metabolic function in central nervous system (CNS) over time is still under study.

Objectives: To compare the effectiveness of fingolimod (FTY) and glatitamer acetate (GA)on myelin repair, tissue integrity and axonal metabolic function over a 24-months follow-up study.

Methods: Eighty five patients with relapsing remitting multiple sclerosis (RRMS) from two different prospective, open-label clinical trials were included and compared over a 24-month period. Mean Expanded Disability Status Scale (EDSS) score was 2.7 (0-6.5) and  1.8 (0-5.5) for FTY and GA respectively. Multi-modal advanced brain magnetic resonance imaging (MRI) including diffuse tensor imaging (DTI), magnetic transfer ration (MTR) and mutli-voxel H-MRS ( magnetic resonance spectroscopy) were obtained at baseline and annually for two years after.

Results: Compared to baseline, whole brain tissue (WBT) MTR was significantly decreased in GA group ( 0.793±1.1, P<0.0005) , showed increment trend in FTY group (-0.004±2.1, P=0.9) with a significant group difference (P=0.034). Tissue integrity, as reflected in fractional anisotropy demonstrated improvement trends, in both groups however it was not statistically significant. (FTY: -0.001 ± 0.002, P = .7; GA: -0.003 ± 0.002, P = .25). There was no significant group difference either (P=0.85).  Group differences did not reach significance for mean diffusivity (MD) (p=0.42).  At year 2,  mean tNAA/tCr did not change statistically among groups (P=0.43 )

Conclusions: This study demonstrates fingolimod promotes remyelination trends in whole brain tissue over time in the CNS. Further longitudinal studies on MTR and DTI in different brain regions and a focus on gray or white matter pathology are warranted to confirm these findings.