Author Of 2 Presentations
LB1219 - Normal serum NFL levels: a proposal of cut-off strategy definition for the clinical practice (ID 2090)
Abstract
Background
Serum Neurofilament light (sNFL) protein is the most promising marker of disease activity and treatment response in Multiple Sclerosis (MS). To implement sNFL in clinical practice, the definition of normal widely accepted values represents a crucial step still to be addressed. Clinically applicable cut-off values need to take into account age dependency; in addition, recent evidences suggest that physical parameters as body mass index (BMI) and blood volume (BV) might influence sNFL levels.
Objectives
The present study aims to address these crucial needs, describing sNFL levels in healthy population, their inter-individual variability in a short-term follow-up and defining reference cut-off values. The final objective is to define a strategy to allow implementation of sNFL in clinical practice.
Methods
We measured sNFL by single molecule array (Simoa) assay (NF-light advantage Kit, Quanterix) in 79 healthy individuals to define reference cut-off values. Age, BMI and BV were correlated with sNFL levels. In addition, sNFL were evaluated after a short-term follow-up time (median 67 days) to assess intra-individual variability: consecutive blood samples were tested in a subset of 27 participants (n=2-4 sample for each individual) and the coefficient of variation (CV) for NFL levels of each participant was evaluated.
sNFL were also tested in 23 naïve MS patients both at diagnostic time and immediately before treatment (median 76 days after) to evaluate the variability of sNFL in patients and the applicability of obtained cut-off values.
Results
1) Our data confirmed a strong correlation between sNFL levels and age. We found a negative correlation between sNFL levels and BV. 2) Short-term follow-up NFL assessments showed an overall intra-individual stability in sNFL levels in healthy population (median CV 15%). 3) We defined specific age decade-related cut-off values. 4) In naïve MS patients, sNFL levels were higher than control values; a high variability between diagnostic time and the beginning of treatment (median CV 39%) was shown. Cut-off values were applied in MS patients to discriminate high from normal sNFL levels: at diagnostic time, 57% of MS patients showed high sNFL levels, while at treatment start, 70% of patients demonstrated normal NFL values.
Conclusions
The present study suggests a strategy to define clinical applicable cut-offs to exploit sNFL as a personalised medicine tool in MS: specific cut-off values were calculated for each age decade. sNFL levels demonstrated an overall intra-individual stability in healthy participants in the short-term: this is relevant for a biomarker of disease activity and treatment response that, if successful, will be serially assessed during patients follow-up.
LB1220 - Real-life experience with sNFL in Multiple Sclerosis patients, as monitoring and treatment decision biomarker (ID 2091)
Abstract
Background
Neurofilament light chain (NFL) are the most promising biomarkers to investigate clinical activity and treatment efficacy in multiple sclerosis (MS), for which, to date, clinical examination and magnetic resonance imaging (MRI) are the only tools available for diagnosis and monitoring. NFL are released upon axonal damage in the cerebrospinal fluid and, in low concentration, in serum (sNFL). Whilst correlation between NFL and clinical outcomes is established, their implementation in clinical practice is still to be addressed.
Objectives
The aim of the present real-life cross-sectional study is to describe sNFL in a large cohort of MS patients as additional measure of disease activity and treatment efficacy.
Methods
We measured sNF-L by single molecule array (Simoa) assay (NF-light advantage kit, Quanterix) in 79 healthy participants and in 961 MS patients (n=1130 samples). sNFL were cross-sectionally evaluated in 830 relapsing remitting (RR), 53 primary progressive (PP) and 78 secondary progressive (SP) MS patients at different disease stages including diagnostic time, immediately before treatment, and during treatment with the main disease modifying treatments (DMTs): Interferon-beta, Glatiramer acetate, DimethylFumarate, Teriflunomide, Natalizumab, Alemtuzumab, Fingolimod, anti-CD20 . Clinical assessment was performed to evaluate correlations between sNFL, MRI and relapses.
Results
1) We established clinically applicable cut-off values for each age decade testing healthy individuals, later used to interpret sNFL levels in individual MS patients. 2) Progressive MS patients showed higher sNF-L levels and a greater prevalence of high sNFL levels (32% in PPMS and 26% in SPMS) relative to RRMS patients (16%), with respect to the previously determined cut-off values. 3) Patients experiencing MRI and/or clinical activity close to NFL dosage (+/-60 days) showed higher levels than stable patients; according to cut-off values, high NFL levels were observed in a substantial percentage of MRI active patients (72%) and clinically active patients (75%). 4) All DMTs notably lower sNF-L in RRMS patients treated for more than 12 months relative to untreated patients; though, 12% of treated patients still demonstrated high NFL levels.
Conclusions
This study provides a real-life picture of sNFL in a large cohort of MS patients. Cut-off values specific for age decade were applied to discriminate patients samples in different contexts, showing correlation with disease subtype, clinical activity and DMTs efficacy. Our study shows that clinically applicable cut-offs can enable the implementation of sNFL in everyday clinical practice in individual patients, demonstrating its potential as monitoring and treatment decision biomarker.