Plasma neurofilament light chain levels in patients with MS switching from injectable therapies to fingolimod

Mult Scler. 2018 Jul;24(8):1046-1054. doi: 10.1177/1352458517715132. Epub 2017 Jun 19.

Abstract

Background: Neurofilament light chain (NFL) is a cerebrospinal fluid (CSF) marker of neuroaxonal damage in multiple sclerosis (MS).

Objective: To determine the correlation of NFL in CSF and serum/plasma, and in plasma after switching from injectable MS therapies to fingolimod.

Methods: A first cohort consisted of MS patients ( n = 39) and neurological disease controls ( n = 27) where CSF and plasma/serum had been collected for diagnostic purposes. A second cohort ( n = 243) consisted of patients from a post-marketing study of fingolimod. NFL was determined with Single Molecule Array (Simoa™) technology (detection threshold 1.95 pg/mL).

Results: Mean NFL pg/mL (standard deviation ( SD)) was 341 (267) and 1475 (2358) in CSF and 8.2 (3.58) and 17.0 (16.94) in serum from controls and MS, respectively. CSF/serum and plasma/serum levels were highly correlated ( n = 66, rho = 0.672, p < 0.0001 and n = 16, rho = 0.684, p = 0.009, respectively). In patients starting fingolimod ( n = 243), mean NFL pg/mL ( SD) in plasma was reduced between baseline (20.4 (10.7)) and at 12 months (13.5 (7.3), p < 3 × 10-6), and levels remained stable at 24 months (13.2 (6.2)).

Conclusion: NFL in serum and CSF are highly correlated and plasma NFL levels decrease after switching to highly effective MS therapy. Blood NFL measurement can be considered as a biomarker for MS therapy response.

Keywords: Multiple sclerosis; beta-interferon; drug response biomarkers; fingolimod; glatiramer acetate; neurofilament.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Female
  • Fingolimod Hydrochloride / therapeutic use*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Middle Aged
  • Multiple Sclerosis / blood*
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / pathology
  • Neurofilament Proteins / blood*
  • Young Adult

Substances

  • Biomarkers
  • Immunosuppressive Agents
  • Neurofilament Proteins
  • neurofilament protein L
  • Fingolimod Hydrochloride