Early neurofilament light chain levels are correlated with brain atrophy up to 4 years in dimethylfumarate treated patients with relapsing remitting multiple sclerosis

Introduction: Dimethyl fumarate (DMF) is widely used in the
treatment of relapsing multiple sclerosis (MS) and has shown a
significant reduction in neurofilament light chain (NFL), new and/
or enlarged white matter lesion and relapses. Relationship between
brain atrophy and levels of NfL during treatment with DMF have
not been examined.
Objectives/Aims: To study the relationship between levels of
NFL and brain atrophy in DMF-treated patients with relapsing
MS.
Methods: The study included 42 treatment naïve newly diagnosed
RRMS patients from the TREMEND trial, a prospective
open label phase IV trial (EudraCT 2014-000254-11) designed to
identify potential biomarkers in DMF-treated patients. At inclusion,
all patients had oligoclonal bands in the CSF and fulfilled
McDonald 2017 criteria. Plasma-NFL levels were measured using
SiMoA at baseline, month 6, 12 and 24. MRI data from baseline
and up to year 4 since DMF initiation were included in the analysis.
Annualized percent brain volume change (aPBVC) was determined
with icobrain using the available MRI data in different year
intervals: [0, 1], [1, 2], [1, 4], [2, 4]. Pearson and Spearman correlations
were determined between NFL levels and aPBVC.
Results: NFL at baseline was significantly correlated with aPBVC
measured during the first treatment year (Pearson-R: -0.41, p:0.04,
N=27) but not with atrophy measured beyond the first year. NFL
measured at 6 months was significantly correlated with aPBVC
measured using MRI data between year 1 and 4 (Spearman-R:
-0.55, p<0.01, N=26). Similarly, NFL measured at 1 year was
significantly correlated with aPBVC measured using MRI data
between year 1 and 4 since DMF start (Spearman-R: -0.39, p:0.04,
Pearson-R:-0.48, p<0.01, N=29). NFL measured at month 24 was
not correlated with any atrophy measures, possibly resulting from
the limited availability of MRI data collected after month 24.
Conclusion: In patients treated with DMF, early on-treatment
plasma NFL levels are associated with subsequent brain atrophy,
reflecting the relationship between active neurodegeneration and
subsequent brain volume loss. Our results suggest that NFL could
be used additional to MRI in the management of MS. High levels
of NFL, particularly in the first year of DMF treatment, are a risk
factor for the subsequent development of brain atrophy.