Abstract Details

Title Baseline Serum Neurofilament Light Chain Levels Predict Conversion to McDonald 2005 Multiple Sclerosis (MS) Within 2 Years of a First Clinical Demyelinating Event in Patients with MS

Topic Multiple Sclerosis

Presentation(s) MS and CNS Inflammatory Disease Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 001

Objective Post hoc analysis to assess whether baseline serum neurofilament light chain (sNfL) concentration can predict conversion to McDonald 2005 multiple sclerosis (MS) in patients with a first clinical demyelinating event (FCDE) receiving subcutaneous interferon β-1a (scIFNβ-1a) once (qw) or three (tiw) times weekly, or placebo in the phase 3 trial REFLEX.

Background sNfL is a biomarker of neuronal damage, reflecting disease activity, drug response, and is predictive of future disability in established MS.

Design/Methods Patients randomized to scIFNβ-1a tiw (n=171), qw (n=175), or placebo (n=171) were followed-up over 2 years; converters to 'clinically definite MS' switched to open label scIFNβ-1a tiw. High and low baseline sNfL subgroups were defined by median sNfL concentration (26.1pg/ml at baseline). Hazard ratios (HR) to determine factors influencing risk of conversion to McDonald MS were calculated using a univariate Cox’s proportional hazard model. A stepwise multivariate Cox’s proportional hazard model was performed using factors selected from univariate analysis (threshold P<0.15).

Results

High sNfL levels at baseline correlated with the likelihood for conversion to McDonald MS (low vs high M0 sNfL, HR [95% confidence interval]: 0.58 [0.47–0.72], P<0.001). Other baseline factors that reduced risk of conversion to McDonald MS: classification of FCDE (mono- vs multifocal: 0.68 [0.55–0.83], P<0.001) and low numbers of MRI lesions (T2 lesions: 1.02 [1.02–1.03]; T1-gadolinium-enhancing lesions: 1.14 [1.11–1.17]; T1-hypointense lesions: 1.04 [1.02–1.05]; P<0.001). scIFNβ-1a tiw (vs placebo: 0.53 [0.41–0.69], P<0.001) or qw (0.71 [0.56–0.91], P=0.006) reduced risk of conversion to McDonald MS. Findings were confirmed by multivariate models for baseline sNfL subgroup (P=0.024), classification of FCDE (P<0.001), most baseline imaging findings (T2- and T1-gadolinium-enhancing lesions (P≤0.001) and on-study treatment (P<0.001).

Conclusions Among other factors, baseline sNfL concentration was identified as a predictor of conversion to McDonald MS in patients with a FCDE.

Authors/Disclosures
Jens Kuhle, MD PRESENTER	Dr. Kuhle has nothing to disclose.
David Leppert, MD (University Hospital Basel)	Dr. Leppert has received personal compensation for serving as an employee of GeNeuro. Dr. Leppert has received personal compensation for serving as an employee of GeNeuro. Dr. Leppert has received personal compensation for serving as an employee of Geneuro. Dr. Leppert has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Leppert has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Leppert has received personal compensation in the range of $0-$499 for serving as a Consultant for Orion. Dr. Leppert has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Leppert has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Quanterix. Dr. Leppert has stock in Novartis.
	No disclosure on file
Nicola De Stefano, MD (University of Siena)	Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck Healthcare KGaA. Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunic AG. Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis Pharma AG. Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck Serono S.p.A. Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche S.p.A.. The institution of Dr. De Stefano has received research support from Italian MS Society. The institution of Dr. De Stefano has received research support from Merck Healthcare KGaA.
Ludwig Kappos, MD, FAAN (RC2NB, University Hospital Basel)	Dr. Kappos has nothing to disclose.
Mark S. Freedman, MD, FAAN (University of Ottawa)	Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Actelion(Janssen/J&J). Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BiogenIdec. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS/Celgene. Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Inc. Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Actelion (Janssen/J&J). Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Atara Biotherapeutics. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer Healthcare. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for BiogenIdec. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Clene Nanomedicine. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GRI Bio. Dr. Freedman 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. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Magenta Therapeutics. Dr. Freedman 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. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Dr. Freedman has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sanofi Genzyme. Dr. Freedman has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. The institution of Dr. Freedman has received research support from Sanofi Genzyme.
Delphine Issard, MD (Merck-Serono S.A)	Dr. Issard has nothing to disclose.
Sanjeev Roy	Sanjeev Roy has received personal compensation for serving as an employee of Merck KgGA.

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