Biomarkers and Bioinformatics Late Breaking Abstracts

LB1221 - Applicability of sNFL in Multiple Sclerosis as additional measure in clinical practice and implications in NEDA-3 evaluation.   (ID 2092)

Speakers
  • A. Bertolotto
Authors
  • A. Bertolotto
  • S. Malucchi
  • F. Marnetto
  • S. Martire
  • P. Valentino
Presentation Number
LB1221
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Despite the increased availability of efficient therapeutic options, early and effective intervention is still mandatory for successful clinical management in Multiple Sclerosis (MS). Speaking of which, a composite measure of disease status termed "no evidence of disease activity" (NEDA) has been proposed as target for treatment in MS. However, this definition needs to be implemented with biological measures for a more personalized medicine. Serum Neurofilament light chain (sNfL) represents the most promising biomarker of disease activity and treatment efficacy in MS, reflecting axonal damage in the central nervous system. To date, sNFL correlation with clinical outcomes is well established in group analysis, yet, its implementation for individual patients is still to be addressed.

Objectives

The aim of the present real-life study is to investigate sNFL as additional measure of treatment efficacy in NEDA-3 patients.

Methods

We measured sNF-L by single molecule array (Simoa) assay (NF-light advantage kit, Quanterix) in 79 healthy participants and in 582 cross-sectionally enrolled RRMS patients, including 61 naive patients, and 521 patients treated with first- or second line therapies, demonstrating NEDA-3 status (no relapses, no disability progression, no MRI activity) during at least 12 months.

Results

1) We established clinically applicable cut-off values for each age decade testing healthy individuals, later used to interpret sNF-L levels in MS patients. 2) In MS patients, treatments notably lower sNF-L relative to untreated patients. 3) According to cut-off values, 53/521 (10%) NEDA-3 patients still demonstrate high NFL levels. These patients were distinguished in different categories: a) patients showing borderline sNFL values; b) patients with concomitant pathologies; c) patients experiencing chronic ongoing fatigability (not classifiable as disability progression); d) patients with a very active disease history; e) patients with conceivable inflammation not detectable by RMN or clinics. 4) The percentage of NEDA-3 patients with high NFL lowers with the extension of NEDA-3 status duration (down to 5% in patients with NEDA-3 status longer than 8 years).

Conclusions

The present cross-sectional study identified a subgroup of NEDA-3 patients showing high sNFL levels. High pathological sNFL levels, reflecting axonal damage, suggest the presence of chronic disease activity or subclinical transitory active inflammation not detectable by RMN or clinics in NEDA-3 patients. The establishment of simple applicable cut-off values allows sNFL applicability in everyday clinical practice. In particular, sNFL could represent an additional measure to be included in NEDA assessment for monitoring therapeutic response in individual MS patients.

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