In vivo Effects of Disease-modifying Therapies on Immunological Subsets in Patients with Relapsing-Remitting Multiple Sclerosis.

Background: Disease-modifying therapies (DMTs) are aimed at controlling Multiple Sclerosis disease by modulating or suppressing the immune system. However, there is limited data on changes in immune cell subsets induced by these treatments.

Objective: To assess differences in myeloid, T-, and B-cell subsets in the peripheral blood of relapsing- remitting MS (RR-MS) patients treated with different DMTs.

Methods: This longitudinal study enrolled all RR-MS patients treated with cladribine (CLAD), dimethyl fumarate (DMF), and natalizumab (NTZ) between July 2022 and September 2022. All patients underwent blood sample collection with flow cytometry at baseline (T0; before starting treatment) and 24 ± 3 months after treatment initiation (T1).

Results: Forty-three RR-MS patients (83.7% women; mean age 34.7 ± 11.1 years; median EDSS: 2.0, IQR: 1.0-2.8) were enrolled. Among them, 24 (55.8%) were treated with DMF, 10 (23.3%) with NTZ, and 9 (20.9%) with CLAD. At T1, patients assigned to CLAD showed a reduction in B-cell memory-switched (p = .029), B-cell memory-unswitched (p = .08), and B-cell naïve resting (p = .029). Additionally, the T and NK cell compartments showed a reduction in the percentage of CD3/CD4/ CD127/CD45RA/CD161+ (p = .057). In the NTZ group, a significant decrease in the percentage of CD3/CD4/CD127/CD45RA/CD161+ (p = .029) was observed. A reduced percentage of mature naïve B cells (p = .057) and B memory-unswitched (p = .059) was observed in the DMF group. No significant differences were found in the myeloid subsets.

Conclusion: DMTs induced significant modifications in B- and T-cell compartments. Characterizing these immunologic changes could deepen our understanding of the mechanisms of action of different therapies.