This cross-sectional evaluation examined the relationship between (a) disability progression from baseline to year-three and (b) sNfL measured at year 3 within RADIEMS, a prospective longitudinal cohort study that enrolled participants soon after MS diagnosis (<5 years). Disability progression was defined by 3 strata EDSS increases from baseline to three-year follow-up (n=108). After generalized linear modeling adjusted sNfL for age, time since diagnosis, and interim inflammatory activity (relapse or MRI activity), non-parametric tests (using SPSS) evaluated differences in sNfL between patients with and without disability progression.

The cohort was 65.7% female, aged 37.4±7.7 years. EDSS worsened in 29 (26.9%) patients. Serum NfL adjusted for age and time since diagnosis was greater in patients with versus without EDSS worsening: median (IQR), 9.39 pg/ml (7.27-11.71) vs. 6.81 (4.88-9.15), p=.001, Cohen’s D=0.66. Additional adjustment for interim inflammatory activity still showed higher sNFL levels among patients with versus without EDSS worsening: 8.54 pg/ml (6.70-12.32) vs. 6.86 pg/ml (4.43-9.93), p=.013, Cohen’s D=0.49.  Magnitude of raw EDSS change from baseline also correlated with higher sNfL levels both adjusted for (r_s=0.278, p=0.004) and unadjusted for (r_s=0.341, p<0.001) interim inflammatory activity.

Serum NfL measurement early in RRMS disease course correlated with worsening EDSS even when controlling for clinical and radiologic activity. This suggests a role for sNfL in identifying patients with disability progression independent of activity in early MS, though further longitudinal study is needed to better assess the predictive value of sNfL over time.