BACKGROUND: Neurofilament light chain (NfL) is a promising marker for predicting disease activity in relapsing multiple sclerosis (RMS). To date, however, there has been no commercially available NfL assay validated in MS and intended for routine clinical use.

OBJECTIVE: To identify and validate a single threshold for NfL in blood that differentiates RMS patients, aged 18-55 years, at a higher versus lower risk of disease activity over 2 years, using the Atellica® IM NfL assay.

METHODS: The optimal NfL threshold for this assay/use case was identified and independently validated using ASCLEPIOS I and II data, respectively. The primary endpoint (annualized number of new/enlarging T2 (neT2) lesions) was analyzed using negative binomial models. Threshold optimization used maximum likelihood methodology. Generalizability analyses used data from ASCLEPIOS II, FREEDOMS, and TRANSFORMS.

RESULTS: NfL concentration of 12.9 pg/mL was validated as the optimal cutoff for prognosticating disease activity as measured by neT2 lesion over 2 years. This threshold prognosticated individual patient risk for persistent disease activity (>3 neT2 lesions/year over 2 years) and showed prognostic value across relevant subgroups and clinical scenarios. Findings for relapses were similar.

CONCLUSION: The CE-marked Atellica® IM NfL assay is now validated for prognostic use in RMS patients.