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

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 1.95pg/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 12months (13.5 (7.3), p<3x10(-6)), and levels remained stable at 24months (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.