Immunological effects of dimethyl fumarate treatment in blood and CSF of patients with primary progressive MS

J Talbot,H Højsgaard Chow,R Holm Hansen,M Rode Von Essen,F Sellebjerg

doi:10.1016/j.jneuroim.2021.577756

Abstract

Dimethyl fumarate is an efficient therapy used widely in patients with relapsing-remitting multiple sclerosis (RRMS). However, lacking effect of treatment has recently been reported in patients with primary progressive MS (PPMS) (Højsgaard Chow et al., 2021). In order to further analyze the immunological treatment response we investigated the systemic and intrathecal immunological effects of dimethyl fumarate (DMF) treatment in 50 patients with PPMS who participated in a 48-week randomized controlled trial with dimethyl fumarate vs placebo. We found substantial systemic immunomodulatory effects of DMF treatment comparable with those observed in patients with RRMS. However, intrathecal effects were limited and restricted to CD4+ T cells presumably resulting in higher concentrations of intrathecal IL-7.

Highlights

Immunosuppressive and immunomodulatory treatment strategies have largely failed in patients with primary progressive multiple scle rosis (PPMS), especially in the later stages of the disease (Sorensen et al, 2020)
Patients treated with dimethyl fumarate (DMF) had lower numbers of CD4+ and CD8+ T cells in blood compared with patients treated with placebo, and there were substantial effects on both effector and regu latory T cell subsets
Therapeutic effects of DMF treatment in cerebrospinal fluid (CSF) were restricted to reduced numbers of CD4+ T cells and increased concen trations of IL-7

Summary

Introduction

Immunosuppressive and immunomodulatory treatment strategies have largely failed in patients with primary progressive multiple scle rosis (PPMS), especially in the later stages of the disease (Sorensen et al, 2020). It is well established that DMF ameliorates clinical and radiological disease activity and disability worsening in patients with relapsingremitting MS (RRMS) (Fox et al, 2012; Gold et al, 2012; Kappos et al, 2008). Patients diagnosed with RRMS treated with DMF show reduced concentrations of CSF NFL and depletion of several immune cell subsets linked to disease activity (Gold et al, 2012; Høglund et al, 2018; Kappos et al, 2008; Sejbaek et al, 2019). We examined immunological effects of DMF on immune cell subsets in CSF and blood. We explored how CSF cytokine and chemokine concentrations respond to DMF treatment in patients with PPMS and analyzed associations be tween effects on cytokine and CSF cells

Methods

Results

Conclusion