Dumitru Ciolac, Felix Luessi, Gabriel Gonzalez-Escamilla, Nabin Koirala, Christian Riedel, Vinzenz Fleischer, Stefan Bittner, Julia Krämer, Sven G. Meuth, Muthuraman Muthuraman, Sergiu Groppa
- Background
Efficient personalized therapy paradigms are needed to modify the disease course and halt gray (GM) and white matter (WM) damage in patients with multiple sclerosis (MS). Presently, promising disease-modifying drugs show impressive efficiency, however, tailored markers of therapy responses are required. Here, we aimed to detect in a real-world setting patients with a more favorable brain network response and immune cell dynamics upon dimethyl fumarate (DMF) treatment.
Methods
In a cohort of 78 MS patients we identified two thoroughly matched groups, based on age, disease duration, disability status and lesion volume, receiving DMF (n = 42) and NAT (n = 36) and followed them over 16 months. The rate of cortical atrophy and deep GM volumes were quantified. GM and WM network responses were characterized by brain modularization as a marker of regional and global structural alterations. In the DMF group, lymphocyte subsets were analyzed by flow cytometry and related toBackground
Efficient personalized therapy paradigms are needed to modify the disease course and halt gray (GM) and white matter (WM) damage in patients with multiple sclerosis (MS). Presently, promising disease-modifying drugs show impressive efficiency, however, tailored markers of therapy responses are required. Here, we aimed to detect in a real-world setting patients with a more favorable brain network response and immune cell dynamics upon dimethyl fumarate (DMF) treatment.
Methods
In a cohort of 78 MS patients we identified two thoroughly matched groups, based on age, disease duration, disability status and lesion volume, receiving DMF (n = 42) and NAT (n = 36) and followed them over 16 months. The rate of cortical atrophy and deep GM volumes were quantified. GM and WM network responses were characterized by brain modularization as a marker of regional and global structural alterations. In the DMF group, lymphocyte subsets were analyzed by flow cytometry and related to clinical and MRI parameters.
Results
Sixty percent (25 patients) of the DMF and 36% (13 patients) of the NAT group had disease activity during the study period. The rate of cortical atrophy was higher in the DMF group (−2.4%) compared to NAT (−2.1%, p < 0.05) group. GM and WM network dynamics presented increased modularization in both groups. When dividing the DMF-treated cohort into patients free of disease activity (n = 17, DMFR) and patients with disease activity (n = 25, DMFNR) these groups differed significantly in CD8+ cell depletion counts (DMFR: 197.7 ± 97.1/μl; DMFNR: 298.4 ± 190.6/μl, p = 0.03) and also in cortical atrophy (DMFR: −1.7%; DMFNR: −3.2%, p = 0.01). DMFR presented reduced longitudinal GM and WM modularization and less atrophy as markers of preserved structural global network integrity in comparison to DMFNR and even NAT patients.
Conclusions
NAT treatment contributes to a reduced rate of cortical atrophy compared to DMF therapy. However, patients under DMF treatment with a stronger CD8+ T cell depletion present a more favorable response in terms of cortical integrity and GM and WM network responses. Our findings may serve as basis for the development of personalized treatment paradigms.…
