Serum Neurofilament Light Chain in Multiple Sclerosis: Superiority of Age‐ and BMI ‐Corrected Z Scores/Percentiles Over Absolute Cutoff Values for Prediction of Treatment Response
Year: 2025
Type: article
Study design: Observational Study
Abstract: OBJECTIVE: Prognostication of disease course and prediction of treatment response in multiple sclerosis is an unmet need. We compared the performance of serum neurofilament light chain Z scores (age- and BMI-adjusted) with absolute concentrations for the prediction of response to disease-modifying therapy. METHODS: Observational cohort study including the first serum sample of participants after the start of fingolimod therapy. We estimated hazard ratios for future relapses comparing participants with high (upper quartile) versus lower neurofilament light chain levels, based on either absolute concentration or Z score cutoffs. We compared the prognostic/predictive performance of these two measures for the occurrence of new/enlarging T2w lesions in longitudinal MRI. RESULTS: We included 447 participants (median [IQR] age, 41.3 [32.1-49.2] years; 65.1% female); median follow-up 8.3 years [6.0-10.3]. Participants with a high neurofilament light chain Z score (Z ≥ 1.2/88.5 percentile) were more likely to experience future relapses (HR: 1.80, 95% CI 1.27-2.54, p < 0.001) compared to those below this threshold while this dichotomy could not be demonstrated with absolute concentration cutoffs (≥ vs. < 10.8 pg/mL; HR: 0.94, 95% CI 0.64-1.38, p = 0.75). Furthermore, patients with upper quartile Z scores were associated with a higher incidence of new/enlarging T2w lesions compared with those below this threshold (OR: 1.88, 95% CI 1.31-2.70, p < 0.001); again, absolute concentration cutoffs failed to identify this risk (OR: 1.20, 95% CI 0.82-1.77, p = 0.34). These findings were confirmed when patients having started alternative oral treatments were also included (n = 713). INTERPRETATION: Serum neurofilament light chain Z scores consistently outperformed absolute concentration cutoffs for prognostication of clinical/radiological disease activity and may facilitate individual prediction of treatment response.
Authors: Maximilian Einsiedler, Aleksandra Maleska Maceski, Sofia Sandgren, Johanna Oechtering, Sabine Schaedelin, Lisa Hofer, Amar Zadic, Juan Francisco Vilchez Gomez, Lester Melie‐Garcia, Alessandro Cagol, Riccardo Galbusera, Sebastian Finkener, Patrice Lalive, Marjolaine Uginet, Stefanie Müller, Caroline Pot, Amandine Mathias, Renaud Du Pasquier, Robert Hoepner, Andrew Chan, Giulio Disanto, Chiara Zecca, Marcus D’Souza, Lars G. Hemkens, Tobias Derfuss, Özgür Yaldizli, Patrick Roth, Claudio Gobbi, David Brassat, Björn Tackenberg, Henrik Zetterberg, Tjalf Ziemssen, Heinz Wiendl, Klaus Berger, Marco Hermesdorf, Fredrik Piehl, Ludwig Kappos, Cristina Granziera, Ahmed Abdelhak, David Leppert, Eline A. J. Willemse, Pascal Benkert, Jens Kuhle, Swiss Multiple Sclerosis Cohort Study (SMSC)
Institutions: University of Basel, University Hospital of Basel, Sahlgrenska University Hospital, Region Västra Götaland, University of Gothenburg, Kantonsspital Aarau, University of Geneva, University Hospital of Geneva, Kantonsspital St. Gallen, Centre Hospitalier Universitaire Vaudois, University of Lausanne, University of Bern, University Hospital of Bern, Università della Svizzera italiana, University of Zurich, University Hospital Zurich, Novartis (Switzerland), Pitié-Salpêtrière Hospital, Roche (Switzerland), Philipps University of Marburg, University of Wisconsin–Madison, UK Dementia Research Institute, National Hospital for Neurology and Neurosurgery, UCL Queen Square Institute of Neurology, University College London, University Hospital Carl Gustav Carus, Technische Universität Dresden, University of Freiburg, University Medical Center Freiburg, University of Münster, Karolinska Institutet, Stockholm Health Care Services, University of California, San Francisco
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,100
Funders: National Science Foundation, Bristol-Myers Squibb, Eli Lilly and Company, Merck, Novartis, Roche, Sanofi, Biogen, Teva Pharmaceutical Industries, Alexion Pharmaceuticals, Celgene, F. Hoffmann-La Roche, University of Wisconsin-Madison, Västra Götalandsregionen, CSL Behring, Universität Basel, European Committee for Treatment and Research in Multiple Sclerosis, University of Bern, Merck KGaA, Novocure, International Progressive MS Alliance, Inselspital, Universitätsspital Bern, Multiple Sclerosis Society, European Commission, National Research Foundation, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Karolinska Institutet, Westfälische Wilhelms-Universität Münster, Sahlgrenska Universitetssjukhuset, Göteborgs Universitet, Université de Genève, Université de Lausanne, Centre Hospitalier Universitaire Vaudois, Universität Zürich, Schweizerische Multiple Sklerose Gesellschaft, Universitätsspital Zürich, Servier, School of Medicine and Public Health, University of Wisconsin-Madison, University of California, San Francisco, Novartis Pharma, Sanofi Genzyme, Sahlgrenska Akademin
Awards: G197559811, G7329429427, G7699452004
OpenAlex ID: W4412947031