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

Introduction: 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. Objectives: 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.