Background: Serum neurofilament light chain (sNfL) has been identified as a useful biomarker for disease activity, prognosis, and treatment response in patients with multiple sclerosis (pwMS). However, its utility in Asian pwMS remains underexplored. This study investigates the predictive value of sNfL for disease activity and long-term disability as well as the applicability of Western-derived z-scores in Korean MS patients.

Methods: We analyzed 169 blood samples from 117 Korean pwMS across three referral hospitals. Baseline samples were obtained within one year of disease onset, with follow-up samples at least three months later. Age- and BMI-adjusted z-scores of baseline sNfL were analyzed for correlations with disease activity and prognosis, while delta z-scores -calculated as the difference between baseline and follow-up z-scores- were used to evaluate disease progression.

Results: Higher baseline sNfL level and z-scores were significantly associated with greater radiological disease activity, including T2 lesion burden and gadolinium-enhancing lesions. Patients with a baseline sNfL z-score >2.86 had a 2.34-fold higher relapse risk within two years. Additionally, a delta z-score <1, reflecting persistently elevated sNfL levels despite disease-modifying treatment, was strongly associated with an increased risk of reaching confirmed EDSS 3 (HR 15.56, 95 % CI 1.49-398.1).

Conclusions: These findings support sNfL as a useful biomarker for predicting disease activity and long-term outcomes in Korean pwMS. Elevated baseline sNfL levels reflect active disease and a higher risk of relapse, while persistently elevated sNfL following treatment initiation is associated with worse long-term disability outcomes.