Clinical validation of a novel in vitro diagnostic neurofilament light chain assay for the prognostication of disease activity in people with relapsing multiple sclerosis.

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.