In multiple sclerosis patients a single serum neurofilament light chain (sNFL) dosage is strongly associated with 12 months outcome: data from a real-life clinical setting.

Background: Neurofilament light chain (NFL) is a neuroaxonal cytoskeletal protein released into cerebrospinal fluid (CSF) and eventually into blood upon neuronal injury. Its detection in serum (sNFL) makes it a promising marker in multiple sclerosis (MS).
Objective: To evaluate the usefulness of a single dosage of sNFL in clinical practice.
Methods: 626 consecutive relapsing-remitting (RR) MS patients treated with disease modifying treatments (DMTs) for at least 12 months underwent a single sNFL dosage. 553 patients had NEDA-3 status (no relapses, no disability progression, no new/enlarging or contrast-enhancing lesions on brain magnetic resonance imaging) in the 12 months prior blood sampling. sNFL levels were measured by single molecule array (Simoa™). Association between sNFL levels and NEDA-3 status at 12, 24, and 36 months was evaluated with logistic regression models adjusted for sex, EDSS, disease duration, and type of DMTs.
Results: 469 out of the 553 NEDA-3 patients had normal sNFL level, whereas 42 had elevated level. The two groups did not differ regarding baseline characteristics. A very strong association between elevated sNFL levels and loss of NEDA-3 status within 12 months was found, with an odds ratio [OR] of 10.74 (95% CI 4.34-26.57); 15 and 10 patients with normal and elevated sNFL, respectively lost NEDA-3 (p < 0.001). The effect was not detected during the subsequent 13-24 and 25-36 months.
Conclusions: A single elevated sNFL is strongly associated with NEDA-3 loss within 1 year. Elevated sNFL in apparently stable patients suggests an ongoing disease activity below the detection threshold of standard parameters.
Competing Interests: Declarations. Conflicts of interest: Malucchi Simona received compensation for speaking and consulting from Biogen, Merck, Novartis, Roche. Valentino Paola received speaker honoraria from Roche, research support from Merck, grant support from Quanterix. Bava Cecilia Irene: nothing to discose. Martire Serena: nothing to disclose. Di Sapio Alessia received compensation for speaking and consulting by Biogen, Novartis, Roche, Sanofi, Alexion, Sandoz and reimbursement by Merck, Biogen, Genzyme and Roche for attending conferences. Lo Re Marianna received compensation for consulting by Novartis. Bertolotto Antonio served on the scientific advisory board of Almirall, Bayer, Biogen, Genzyme; received speaker honoraria from Biogen, Novartis, Sanofi, grant support from Almiral, Biogen, Associazione San Luigi Gonzaga ONLUS, Fondazione per la Ricerca Biomedica ONLUS, Mylan, Novartis and the Italian Multiple sclerosis Society. Ethical approval: The study was approved by the ethical committee of San Luigi Gonzaga University Hospital (approvals number 7262/2019 and 18,390/2019). All participants provided informed consent.
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