Abstract Details

Title Trajectories of Serum NfL and GFAP Levels in Newly Diagnosed Multiple Sclerosis Patients After Initiation of Immunomodulatory Treatments

Topic Multiple Sclerosis

Presentation(s) P6 - Poster Session 6 (11:45 AM-12:45 PM)

Poster/Presentation
Number 1-012

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.

Authors/Disclosures
Tomas Uher PRESENTER	Tomas Uher has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Tomas Uher has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol myers. Tomas Uher has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Tomas Uher has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. The institution of Tomas Uher has received research support from Novartis.
Václav Čapek, PhD	Dr. Capek has nothing to disclose.
Aleksandra Maceski	Aleksandra Maceski has nothing to disclose.
Pascal Benkert	Pascal Benkert has nothing to disclose.
Barbora Srpova, MD, PhD	Mrs. Srpova has nothing to disclose.
Manuela Vaneckova	Manuela Vaneckova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis . Manuela Vaneckova has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Manuela Vaneckova has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Manuela Vaneckova has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. The institution of Manuela Vaneckova has received research support from Czech Ministry of Health project—grants NU 22-04-00193 . Manuela Vaneckova has received research support from Czech Ministry of Health project - RVO VFN 64165 . Manuela Vaneckova has received personal compensation in the range of $500-$4,999 for serving as a principal investigator with Czech Ministry of Health project—grants NU 22-04-00193 .
Eva Havrdova, MD (Neurologicka Klinika 1 LF UK)	Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi.
Dana Horakova	Dana Horakova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dana Horakova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dana Horakova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dana Horakova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck.
Jens Kuhle, MD	Dr. Kuhle has nothing to disclose.

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