sNfL is associated with disease activity, predicts clinical and imaging outcomes, and is reduced by disease-modifying treatments (DMTs) in RRMS patients. Integration of sNfL into clinical practice requires a standardized validated assay and establishing clinically-meaningful cutpoints.

sNfL was measured with a SIMOA NF-light® Advantage Kit (Quanterix) or laboratory method in serial samples from >1400 patients in 4 studies. In ADVANCE [peginterferon beta-1a, RRMS, n=859], sNfL was measured at baseline, every 3 months until year 2, then every 6 months until year 4; in CHAMPS [interferon beta 1a (IFNβ1a), clinically isolated syndrome, n=319], at baseline and week 48; in MSCRG (IFNβ1a, RRMS, n=164), at years 3 and 4; and in SENTINEL (natalizumab, RRMS, n=122), at baseline and week 96. Statistical analyses included Spearman correlation, ANOVA, chi-squared test, Kaplan-Meier analysis, and multivariate logistic regression.

Baseline sNfL levels were associated (p<0.0001) with number of enhancing lesions and accumulation of new T2 lesions over time. sNfL>16 pg/mL indicated high probability of disease activity over the following year (PPV=91%); combining multiple sNfL measurements (BL, Months 3 and 6) improved PPV from 91% to 94%. sNfL>16 pg/mL was associated long-term with worse outcomes: EDSS progression (12 years, p<0.05), T2 lesion volume (10 years, p<0.00001), and brain atrophy (5 years p<0.00001). sNfL levels were lowered by DMTs; natalizumab reduced sNfL <16 pg/mL in 96% of patients. Plans for introducing sNfL into clinical practice will also be presented. 

These findings support clinical relevance of sNfL levels and demonstrate feasibility of establishing relevant cut-points for disease severity stratification and treatment monitoring in RRMS patients.  Establishing a standardized, widely accessible assay and validating sNfL in real-world cohorts are essential next steps for implementation of sNfL into clinical practice.