Serum neurofilament light chain in paediatric patients treated with natalizumab for highly active multiple sclerosis

Natalizumab (NTZ) effectively suppresses clinical and radiologic disease activity in paediatric patients with multiple sclerosis (MS), however, it is unclear whether serum neurofilament light chain (sNfL), a biomarker of neuronal injury, normalizes.

To evaluate sNfL response to NTZ in the paediatric setting.

sNfL was measured (single-molecule array) in 66 paediatric patients on NTZ for highly active MS in a single-centre between 2007 and 2023. sNfL levels were converted to age-adjusted z-scores for longitudinal assessment.

sNfL declined significantly on NTZ, however, not all patients achieved normalized levels. Percentage of patients with sNfL < 90th percentile of healthy aged-matched individuals increased from 6.8% initially to 50%, 65% and 75% within 12, 24 and 36 treatment-months, respectively. Higher on-treatment levels were associated with higher baseline levels (B = 0.791, p < 0.001) and John Cunningham virus (JCV) seropositivity (B = 0.286, p < 0.001). sNfL > 97th percentile at 12 treatment-months indicated greater likelihood of disease activity in following year.

NTZ treatment resulted in a significant reduction in sNfL levels, correlating with its clinical efficacy in paediatric MS. However, higher baseline sNfL concentrations were associated with a prolonged time to normalization. In addition, JCV seropositivity was linked to elevated NfL levels during treatment.