Low serum neurofilament light chain values identify optimal responders to dimethyl fumarate in multiple sclerosis treatment

Paulette Esperanza Walo-Delgado,Jaime Masjuan-Vallejo,Luisa María Villar,Lucienne Costa-Frossard,Eulalia Rodríguez-Martín,Daniel Lourido,Mercedes Espiño,Silvia Medina,Noelia Villarrubia,Ernesto Roldán,Enric Monreal,Alfonso Muriel,José Ignacio Fernández-Velasco,Susana Sainz De La Maza

doi:10.1038/s41598-021-88624-7

Abstract

Serum neurofilament light chains (sNfL) are biomarkers of disease activity in multiple sclerosis (MS), but their value to predict response to treatment, and their association with patient immunological profile, need to be further explored. We studied 80 relapsing–remitting MS patients initiating dimethyl fumarate (DMF) treatment. sNfL levels were explored at baseline and at 3, 6 and 12 months by single molecule array. Blood lymphocyte subsets were measured at baseline and at 6 months by flow cytometry. Patients were followed a year and classified as NEDA (no evidence of disease activity) or ODA (ongoing disease activity). NEDA patients had lower sNfL levels at baseline (p = 0.0001), and after three (p = 0.004) and six (p = 0.03) months of DMF treatment. Consequently, low baseline sNfL values (≤ 12 pg/ml) increased the probability of NEDA (OR 5.8; CI 1.82–15.6; p = 0.002, after correcting by disease activity in the previous year), and associated with significant reductions of central memory CD4+ T lymphocytes, interferon-gamma+ CD8+ T lymphocytes, Natural Killer T cells, and memory B cells upon DMF treatment, being the highest differences in memory B cells (p < 0.0001). This shows that low baseline sNfL values identify MS patients with higher probability of optimal response to DMF and of a reduction in effector immune cells.

Highlights

Serum neurofilament light chains are biomarkers of disease activity in multiple sclerosis (MS), but their value to predict response to treatment, and their association with patient immunological profile, need to be further explored
After performing a multivariate analysis and adjusting results by presence of baseline Gd+ enhancing lesions, number of Gd+ enhancing lesions and of no evidence of disease activity (NEDA) status in the previous year, we found that Serum neurofilament light chains (sNfL) ≤ 12 pg/ml at baseline maintained its ability in predicting NEDA at 12 months
dimethyl fumarate (DMF) has been shown to be an effective drug in the treatment of relapsing remitting multiple sclerosis (RRMS) patients with intermediate disease activity[14]

Summary

Introduction

Serum neurofilament light chains (sNfL) are biomarkers of disease activity in multiple sclerosis (MS), but their value to predict response to treatment, and their association with patient immunological profile, need to be further explored. Low baseline sNfL values (≤ 12 pg/ml) increased the probability of NEDA (OR 5.8; CI 1.82–15.6; p = 0.002, after correcting by disease activity in the previous year), and associated with significant reductions of central memory CD4+ T lymphocytes, interferon-gamma+ CD8+ T lymphocytes, Natural Killer T cells, and memory B cells upon DMF treatment, being the highest differences in memory B cells (p < 0.0001). DMF demonstrated efficacy in ameliorating disease course in RRMS patients in two large 2-year double-blind, multinational, phase III trials, DEFINE1 and C ONFIRM2 and their dose-blind extension, ENDORSE3,4 Optimal responders to this drug show a shift from an inflammatory to a tolerogenic blood cell profile[5].

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