jueves, 14 de noviembre de 2019

Dimethyl fumarate decreases neurofilament light chain in CSF and blood of treatment naïve relapsing MS patients. - PubMed - NCBI

2019 Oct 13. pii: jnnp-2019-321321. doi: 10.1136/jnnp-2019-321321. [Epub ahead of print]

Dimethyl fumarate decreases neurofilament light chain in CSF and blood of treatment naïve relapsing MS patients.

Sejbaek T1,2,3,4,5, Nielsen HH6,2,5, Penner N7, Plavina T7, Mendoza JP7, Martin NA2, Elkjaer ML6,2, Ravnborg MH6, Illes Z6,2,5.

Author information

1: Neurology, Odense Universitetshospital, Odense, Denmark Tobias.Sejbaek.Mathiesen@rsyd.dk.
2: Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
3: Neurology, Hospital of South West Jutland, Esbjerg, Denmark.
4: The Department of Regional Health Research, University of Southern Denmark, Odense, Denmark.
5: MS Alliance of Southern Denmark, Esbjerg, Denmark.
6: Neurology, Odense Universitetshospital, Odense, Denmark.
7: Value Based Medicine, Biogen Idec Inc, Cambridge, Massachusetts, USA.

Abstract

OBJECTIVES:

In a prospective phase IV trial of the first-line oral treatment dimethyl fumarate (DMF), we examined dynamics of neurofilament light (NFL) chain in serum, plasma and cerebrospinal fluid (CSF) samples collected over 12 months from relapsing-remitting multiple sclerosis (RRMS) patients. NFL changes were related to disease activity.

METHODS:

We examined NFL levels by single-molecule array in 88 CSF, 348 plasma and 131 sera from treatment-naïve RRMS patients (n=52), healthy controls (n=23) and a placebo group matched by age, sex and NFL (n=52). Plasma/sera were collected at baseline, and 1, 3, 6 and 12 months after DMF. CSF samples were collected at baseline and 12 months after DMF.

RESULTS:

NFL concentration in CSF, plasma and serum correlated highly (p<0.0001 for all), but plasma levels were only 76.9% of paired serum concentration. After 12 months of DMF treatment, NFL concentration decreased by 73%, 69% and 55% in the CSF, serum and plasma (p<0.0001, respectively). Significant reduction in blood was observed after 6 and 12 months treatment compared with baseline (p<0.01 and p<0.0001, respectively) and to placebo (p<0.0001). Patients with NFL above the 807.5 pg/mL cut-off in CSF had 5.0-times relative risk of disease activity (p<0.001).

CONCLUSIONS:

This study provides Class II evidence that first-line DMF reduces NFL in both blood and CSF after 6 months and normalises CSF levels in 73% of patients. High NFL concentration in CSF after a year reflected disease activity. NFL levels were higher in serum than in plasma, which should be considered when NFL is used as a biomarker.