Clinical validation of a novel in vitro diagnostic neurofilament light chain assay for the prognostication of disease activity in people with relapsing multiple sclerosis
Ziemssen, Tjalf (University Clinic Carl Gustav Carus, TU Dresden)
Freedman, Mark S. (University of Ottawa)
Bar-Or, Amit (University of Pennsylvania)
Montalban, Xavier (Universitat Autònoma de Barcelona. Departament de Medicina)
Teunissen, Charlotte E. (Vrije Universiteit Amsterdam)
Häring, Dieter A. (Novartis Pharma AG (Basel, Suïssa))
Kukkaro, Petra (Novartis Pharma AG (Basel, Suïssa))
Merschhemke, Martin (Novartis Pharma AG (Basel, Suïssa))
Kieseier, Bernd C. (Novartis Pharma AG (Basel, Suïssa))
Karnik-Henry, Meghana (Siemens Healthineers)
Gee, Matthew (Siemens Healthineers)
Lange, Sascha (Siemens Healthineers)
Merabet, Eddine (Siemens Healthineers)
Chitnis, Tanuja (Brigham and Women's Hospital (Boston, Estats Units d'Amèrica))
Bittner, Stefan (University Medical Center of the Johannes Gutenberg University Mainz (Alemanya))
Wiendl, Heinz (Universitätsklinikum Freiburg)
Hauser, Stephen L. (University of California San Francisco)

Fecha:	2025
Resumen:	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. 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. 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. 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.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Atellica ® IM NfL assay ; Blood biomarkers ; Disease activity ; Multiple sclerosis ; Neurofilament light chain ; new or enlarging T2 lesions ; Prognosis ; Threshold
Publicado en:	Multiple sclerosis, Vol. 31, Num. 13 (November 2025) , p. 1543-1556, ISSN 1477-0970

DOI: 10.1177/13524585251389797
PMID: 41159484

14 p, 1.4 MB

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