Increased Within-Network Functional Connectivity May Predict NEDA Status in Fingolimod-Treated MS Patients.

Only a few studies have evaluated the brain functional changes associated with disease-modifying therapies (DMTs) in multiple sclerosis (MS), though none used a composite measure of clinical and MRI outcomes to evaluate DMT-related brain functional connectivity (FC) measures predictive of short-term outcome. Therefore, we investigated the following: (1) baseline FC differences between patients who showed evidence of disease activity after a specific DMT and those who did not; (2) DMT-related effects on FC, and; (3) possible relationships between DMT-related FC changes and changes in performance. We used a previously analyzed dataset of 30 relapsing MS patients who underwent fingolimod treatment for 6 months and applied the "no evidence of disease activity" (NEDA-3) status as a clinical response indicator of treatment efficacy. Resting-state fMRI data were analyzed to obtain within- and between-network FC measures. After therapy, 14 patients achieved NEDA-3 status (hereinafter NEDA), while 16 did not (EDA). The two groups significantly differed at baseline, with the NEDA group having higher within-network FC in the anterior and posterior default mode, auditory, orbitofrontal, and right frontoparietal networks than the EDA. After therapy, NEDA showed significantly reduced within-network FC in the posterior default mode and left frontoparietal networks and increased between-network FC in the posterior default mode/orbitofrontal networks; they also showed PASAT improvement, which was correlated with greater within-network FC decrease in the posterior default mode network and with greater between-network FC increase. No significant longitudinal FC changes were found in the EDA. Taken together, these findings suggest that NEDA status after fingolimod is related to higher within-network FC at baseline and to a consistent functional reorganization after therapy.

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Copyright © 2021 Piervincenzi, Petsas, De Giglio, Carmellini, Giannì, Tommasin, Pozzilli and Pantano.

Déclaration de conflit d'intérêts

The dataset used in the present work comes from a previous study (9) that received financial support from Novartis Farma, Italy. NP received speaker fees from Biogen Idec and mission support from Merck Serono, Genzyme, and Novartis. LD received speaking honoraria from Genzyme and Novartis; travel grants from Biogen Idec, Merck Serono, and Teva; and consulting fees from Genzyme, Merck Serono, and Novartis. CPo received consulting and lecture fees from Sanofi-Aventis, Biogen Idec, Bayer Schering, Merck Serono, and Novartis. He also received research funding from Novartis, Sanofi-Aventis, Merck Serono, and Bayer Schering. PP received travel funding from Novartis, Genzyme, and Bracco and speaker honoraria from Biogen Idec. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.