Plasma neurofilament light chain to evaluate response during cladribine treatment in multiple sclerosis. 2025

Valerio Nicolella, and Marco Varelli, and Stefania Fasano, and Enrico Cantone, and Carmela Polito, and Rosa Sirica, and Evelina La Civita, and Mariano Fiorenza, and Federica Novarella, and Giuseppe Corsini, and Antonio Carotenuto, and Maria Petracca, and Roberta Lanzillo, and Vincenzo Brescia Morra, and Giuseppe Castaldo, and Daniela Terracciano, and Marcello Moccia
Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy.

BACKGROUND Cladribine treatment in year 1 and 2 provides high efficacy on multiple sclerosis(MS) outcomes over 4 years. Use of biomarkers of neuro-axonal damage, such as plasma neurofilament light chain (pNfL), might support prognostication and treatment decisions. OBJECTIVE To:1)investigate pNfL variations over time in people with MS(pwMS) treated with cladribine;2)compare pNfL levels during cladribine treatment to age- and sex-matched controls;3) assess pNfL prediction on clinical and radiological outcomes. METHODS This retrospective analysis of longitudinally-collected data included 258 pwMS treated with cladribine and 304 age and sex-matched controls. During follow-up,in pwMS,we collected evidence of disease activity (EDA3). RESULTS When compared with pNfL before or in the first 3 months of treatment,pNfL was lower between 3 and 12 months(Coeff = -182.05; 95 %CI = -303.73, -60.36; p = 0.004), between 12 and 24 months (Coeff = -149.98; 95 %CI = -272.41, -27.55; p = 0.017) and after 24 months from the first cladribine dosing (Coeff = -280.32; 95 %CI = -280.32,-29.86; p = 0.016). When compared with controls,pNfL was higher in pwMS before or in the first 3 months of cladribine treatment(Coeff = 7.43; 95 %CI = 2.45, 12.40; p = 0.004), but was similar between 3 and 12 months(Coeff = -1.04; 95 %CI = -3.36, 1.27; p- = 0.376), between 12 and 24 months(Coeff = 1.48; 95 %CI = -0.60, 3.55; p = 0.162) and after 24 months(Coeff = 2.23; 95 %CI = -0.47, 5.08; p = 0.103). We observed no significant associations between baseline pNfL and EDA(11 patients,4.26 %). CONCLUSIONS Cladribine significantly reduced pNfL levels, which stabilized at values comparable to matched healthy controls, confirming its strong efficacy with minimal disease activity during follow-up.

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