Abstract Details

Title Neurofilament-Light Chain Levels Are Predictive of On-going Disease Activity in Radiologically Isolated Syndrome

Topic Multiple Sclerosis

Presentation(s) S37 - MS Biomarkers (1:22 PM-1:33 PM)

Poster/Presentation
Number 003

Background EDA (new MRI lesions and/or a clinical event) is a characteristic feature of multiple sclerosis (MS), associated with an increased risk of relapse. In addition to younger age, male sex and spinal cord lesion(s), elevated cerebrospinal fluid (CSF) NfL and presence of immunoglobulin G oligoclonal bands (OCB) were recently identified as predictive of CC in RIS subjects.

Objective To evaluate the predictive value of neurofilament-light chain (sNfL) on the risk of evidence of disease activity (EDA) and of clinical conversion (CC) in patients with radiologically isolated syndrome (RIS).

Design/Methods We measured sNfL and CSF NfL levels by single molecule array (Simoa, Quanterix) in RIS patients as defined by 2009 RIS criteria. We analysed the influence of age, sex, 2005 dissemination in space (DIS) criteria, spinal cord lesion, gadolinium-enhanced lesion, OCB, sNfL and CSF NfL on the risk of EDA and of CC using Kaplan-Meier analysis and Cox regression models.

Results

62 RIS patients were included from 4 MS centres. Mean follow-up time was 45 months. CSF NfL and sNfL levels at inclusion were highly correlated (Spearman, r=0.783). Kaplan-Meier analysis revealed that presence of OCB, CSF NfL>400pg/mL, sNfL>6.5pg/mL and presence of 4/4 2005 DIS criteria were predictive of disease activity (log rank, p=0.017, p=0.022, p=0.025 and p=0.45, respectively). Especially, patients with 4/4 2005 DIS criteria and/or sNfL>6.5pg/mL had an 86% risk of EDA compared to 54% without these characteristics. Only CSF NfL levels predicted CC during follow-up (log rank, p=0.033). Multivariate Cox regression model revealed that OCB, MRI criteria and sNfL>6.5pg/mL were independent factors of EDA (HR=1.87, p=0.047; HR=2.21, p=0.025 and HR=2.19, p=0.019, respectively), but not of CC.

Conclusions

Elevated sNfL, OCB and 2005 MRI criteria are predictive of EDA in RIS. If replicated in larger datasets, these biomarkers may inform on treatment decisions in this highly relevant population.

On behalf of RISC and SFSEP.

Authors/Disclosures
Eric Thouvenot, MD, PhD (CHU De Nimes - Hopital Caremeau) PRESENTER	Dr. Thouvenot has received personal compensation in the range of $0-$499 for serving as a Consultant for Biogen. Dr. Thouvenot has received personal compensation in the range of $0-$499 for serving as a Consultant for Merck. Dr. Thouvenot has received personal compensation in the range of $0-$499 for serving as a Consultant for Teva. Dr. Thouvenot has received personal compensation in the range of $0-$499 for serving as a Consultant for Novartis. Dr. Thouvenot has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Thouvenot has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Thouvenot has received research support from Biogen. The institution of Dr. Thouvenot has received research support from Novartis. The institution of Dr. Thouvenot has received research support from Roche.
	No disclosure on file
Ugur Uygunoglu (Cerrahpasa)	Ugur Uygunoglu has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Turkey . The institution of Ugur Uygunoglu has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Ugur Uygunoglu has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen Idec/Gen Pharma of Turkey. The institution of Ugur Uygunoglu has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck-Serono of Turkey. The institution of Ugur Uygunoglu has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanovel of Turkey. The institution of Ugur Uygunoglu has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Genveon of Turkey.
Sophie Pittion (Hopital Central/ Service Du Pr Vespignani)	Sophie Pittion has nothing to disclose.
Giovanni Castelnovo	No disclosure on file
	No disclosure on file
Mikael Cohen (Hopital Pasteur)	Mikael Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen, Roche, Merck, Ad scientiam, Novartis, Alexion, BMS.
Darin T. Okuda, MD, FAAN (UT Southwestern Medical Center)	Dr. Okuda has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Okuda has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Cortechs AI. Dr. Okuda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Okuda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Okuda has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Okuda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Moderna. Dr. Okuda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for RVL Pharmaceuticals, Inc.. Dr. Okuda has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Okuda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer. Dr. Okuda has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Zenas BioPharma. Dr. Okuda has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. The institution of Dr. Okuda has received research support from Novartis. The institution of Dr. Okuda has received research support from EMD Serono. Dr. Okuda has received intellectual property interests from a discovery or technology relating to health care.
Orhun H. Kantarci, MD	Dr. Kantarci has nothing to disclose.
Daniel Pelletier, MD (Keck School of Medicine of USC)	Dr. Pelletier has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Pelletier has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi Genzyme. Dr. Pelletier has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Pelletier has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Polpharma Biologics.
	No disclosure on file
	No disclosure on file
Aksel Siva, MD (Istanbul University Cerrahpasa School of Medicine)	Dr. Siva has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Siva has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Siva has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Siva has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen - TR. Dr. Siva has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Siva has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ali Raif Pharmaceuticals, Turkiye. Dr. Siva has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanovel Pharmaceuticals, Turkiye. Dr. Siva has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Siva has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abdi Ibrahim Ilac - TR. Dr. Siva has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck Serono . The institution of Dr. Siva has received research support from Turkish MS Society. The institution of Dr. Siva has received research support from The Scientific and Technological Research Council Of Turkey - Health Sciences Research Grants.
Christine Lebrun Frenay, MD, FAAN (CRCSEP Neurologie)	Dr. Lebrun Frenay has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Revue Neurologique.

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