Objective:

This study aimed to describe the dynamics of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels and explore their association with disease activity in multiple sclerosis (MS). 

Background:

The clinical relevance of sNfL and sGFAP concentrations after the initiation of disease-modifying treatments (DMT) remains unclear.

Design/Methods:

We measured sNfL and sGFAP concentrations in 106 patients at the time of diagnosis, followed by 4-6 time points within 12 months after DMT initiation (687 measurements) using the Simoa method. Hierarchical cluster analysis identified patient subgroups with distinct trajectories of sNfL and sGFAP Z scores, adjusted for age, BMI, and sex in the case of sGFAP. The models were additionally adjusted for sex, age, BMI, DMT type, and relapses.

Results:

The cohort was 75% female, with a median Expanded Disability Status Scale (EDSS) of 2.0 (range 0-4.5), a mean age of 33.6±8.2 years at baseline and a follow-up duration 4.8±1.0 years. Four distinct clusters of sNfL trajectories were identified. In cluster 1 (n=25), sNfL Z scores were initially high but decreased to normal (p<0.001). Cluster 2 (n=10) showed a decrease in high sNfL  Z scores (p<0.001), but the levels remained elevated. Cluster 3 (n=44) had stable, low sNfL Z scores (p>0.05), while cluster 4 (n=27) showed a mild increase in initially low sNfL Z scores (p<0.001). sGFAP  Z scores were stable in two clusters (n=53 and 14; p=0.10-0.91) but increased in one cluster (n=36) following treatment initiation (p=0.008). Higher sNfL Z scores at 12 months predicted a shorter time to relapse (HR=1.67; 95% CI: 1.02-2.74; p=0.045). The cluster with increasing sGFAP Z scores showed a trend toward a higher risk of EDSS worsening (p=0.065).

Conclusions:

While sNfL levels decreased in most newly diagnosed patients after DMT initiation, sGFAP levels remained unchanged or increased, for reasons that are still unknown and warrant further investigation.