Effects of Fingolimod and Natalizumab on Brain T1-/T2-Weighted and Magnetization Transfer Ratios: a 2-Year Study

Fingolimod and natalizumab significantly reduce disease activity in relapsing-remitting multiple sclerosis (RRMS) and could promote tissue repair and neuroprotection. The ratio between conventional T1- and T2-weighted sequences (T1w/T2w-ratio) and magnetization transfer ratio (MTR) allow to quantify brain microstructural tissue abnormalities. Here, we compared fingolimod and natalizumab effects on brain T1w/T2w-ratio and MTR in RRMS over 2 years of treatment. RRMS patients starting fingolimod ( n = 25) or natalizumab ( n = 30) underwent 3T brain MRI scans at baseline (T0), month 6 (M6), month 12 (M12), and month 24 (M24). White matter (WM) lesions, normal-appearing (NA) WM, and gray matter (GM) T1w/T2w-ratio and MTR were estimated and compared between groups using linear mixed models. No baseline demographic, clinical, and MRI difference was found between groups. In natalizumab patients, lesion T1w/T2w-ratio and MTR significantly increased at M6 vs. T0 ( p ≤ 0.035) and decreased at subsequent timepoints ( p ≤ 0.037). In fingolimod patients, lesion T1w/T2w-ratio increased at M12 vs. T0 ( p = 0.010), while MTR gradually increased at subsequent timepoints vs. T0 ( p ≤ 0.027). Natalizumab stabilized NAWM and GM T1w/T2w-ratio and MTR. In fingolimod patients, NAWM T1w/T2w-ratio and MTR significantly increased at M24 vs. M12 ( p ≤ 0.001). A significant GM T1w/T2w-ratio decrease at M6 vs. T0 ( p = 0.014) and increase at M24 vs. M6 ( p = 0.008) occurred, whereas GM MTR was significantly higher at M24 vs. previous timepoints ( p ≤ 0.017) with significant between-group differences ( p ≤ 0.034). Natalizumab may promote an early recovery of lesional damage and prevent microstructural damage accumulation in NAWM and GM during the first 2 years of treatment. Fingolimod enhances tissue damage recovery being visible after 6 months in lesions and after 2 years in NAWM and GM.