A two-year study using cerebral gray matter volume to assess the response to fingolimod therapy in multiple sclerosis.

Background: Cerebral gray matter (GM) atrophy has clinical relevance in multiple sclerosis (MS). Fingolimod has known efficacy on clinical and conventional MRI findings in MS; the effect on GM is unknown.

Objective: To explore fingolimod's treatment effect on cerebral GM atrophy over two years in patients with relapsing forms of MS.

Methods: Patients starting fingolimod [n=24, age (mean±SD) 41.2±11.6years, Expanded Disability Status Scale (EDSS) score 1.1±1.4; 58% women] were compared to untreated patients [n=29, age 45.7±8.4years, EDSS 1.0±1.2; 93% women]. Baseline, one and two year MRI was applied to an SPM12 pipeline to assess brain parenchymal fraction (BPF) and cortical GM fraction (cGMF). T2 lesion volume (T2LV) and gadolinium-enhancing lesions were assessed. Change was modeled using a mixed effects linear regression with a random intercept and fixed effects for time, group, and the time-by-group interaction. The group slope difference was assessed using the interaction term.

Results: Over two years, cGMF remained stable in the fingolimod group (p>0.05), but decreased in the untreated group (p<0.001) (group difference p<0.001). BPF change did not differ between groups (all time-points p>0.05). T2LV increased over two years in the untreated group (p<0.001) but not in the fingolimod group (p≥0.44) (group difference p<0.001).

Conclusions: These results suggest a treatment effect of fingolimod on cerebral GM atrophy in the first two years. GM atrophy is more sensitive to such effects than whole brain atrophy. However, due to the non-randomized, retrospective design, heterogeneous between-group characteristics, and small sample size, these results require confirmation in future studies.