To evaluate the prognostic value of serum neurofilament light chain (sNfL) for future disease activity according to body mass index (BMI) and age in people with relapsing multiple sclerosis (pwRMS).

In the Phase 3 ASCLEPIOS I/II trials (ofatumumab versus teriflunomide [pwRMS aged 18–55]), sNfL levels were prognostic for on-study lesion formation and brain volume loss in the overall and recently diagnosed treatment-naive populations. Age and BMI may affect sNfL levels.

A baseline sNfL cut-off was predefined by the median sNfL value across ASCLEPIOS I/II and participants were stratified into high (≥median [9.3 pg/mL]) and low (<9.3 pg/mL) groups, irrespective of treatment received. The prognostic value of high versus low baseline sNfL for the annualized rate of new/enlarging T2 (neT2) lesions was assessed in baseline BMI [<24.5 versus ≥24.5 kg/m²] and age [<38 versus ≥38 years] subgroups. Negative binomial regression model adjusting for sNfL group, and sNfL group by BMI/age subgroup interaction, were used to estimate the lesion rate ratio (RR) for high versus low sNfL levels in each BMI/age subgroup.

Of the 1,882 participants randomized in ASCLEPIOS I/II, 1,678 (89.2%) had baseline sNfL and neT2 data available. In both BMI subgroups (<24.5 and ≥24.5 kg/m²), participants with high versus low sNfL had a higher mean annualized rate of neT2 lesions (BMI <24.5: 4.04 versus 2.10, RR: 1.92; BMI ≥24.5: 4.14 versus 1.66, RR: 2.49; p<0.001 for both). In both age subgroups (<38 and ≥38 years), participants with high versus low sNfL had a higher mean annualized rate of neT2 lesions (<38: 5.68 versus 2.91, RR: 1.95; ≥38: 2.50 versus 0.94, RR: 2.66; p<0.001 for both).

Baseline sNfL levels were prognostic of future lesion formation irrespective of baseline BMI and age, supporting the use of sNfL as a prognostic biomarker for RMS disease activity.