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.
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Einsiedler Maximilian, Maceski Aleksandra Maleska, Sandgren Sofia, Oechtering Johanna, Schaedelin Sabine, Hofer Lisa, Zadic Amar, Gomez Juan Francisco Vilchez, Melie-Garcia Lester, Cagol Alessandro, Galbusera Riccardo, Finkener Sebastian, Lalive Patrice, Uginet Marjolaine, Müller Stefanie, Pot Caroline, Mathias Amandine, Du Pasquier Renaud, Hoepner Robert, Chan Andrew, Disanto Giulio, Zecca Chiara, D'Souza Marcus, Hemkens Lars G, Derfuss Tobias, Yaldizli Özgür, Roth Patrick, Gobbi Claudio, Brassat David, Tackenberg Björn, Zetterberg Henrik, Ziemssen Tjalf, Wiendl Heinz, Berger Klaus, Hermesdorf Marco, Piehl Fredrik, Kappos Ludwig, Granziera Cristina, Abdelhak Ahmed, Leppert David, Willemse Eline A J, Benkert Pascal, Kuhle Jens, Swiss Multiple Sclerosis Cohort Study (SMSC)
Аннотация
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.