Abstract Details

Title Effect of Interferon ß-1a Treatment on Serum Neurofilament Light Chain Levels in Patients with a First Clinical Demyelinating Event

Topic Multiple Sclerosis

Presentation(s) S5 - Multiple Sclerosis: Clinical Trials and Disease-modifying Therapy (1:36 PM-1:48 PM)

Poster/Presentation
Number 004

Objective Assess effect of subcutaneous interferon β-1a (scIFN β-1a) 44μg once (qw) or three (tiw) times weekly versus placebo on serum Neurofilament light chain (NfL; a promising marker of neuronal injury) in patients with first clinical demyelinating event (FCDE) during REFLEX. Explore the predictive value of NfL for conversion to McDonald 2005 multiple sclerosis (MS).

Background In REFLEX, patients with FCDE treated with scIFNβ-1a 44μg tiw/qw demonstrated delayed conversion to McDonald 2005 MS.

Design/Methods Patients were randomized to scIFNβ-1a tiw/qw, or placebo over 2-years; those who converted to clinically definite MS (CDMS) switched to open label scIFNβ-1a tiw (this analysis only included data collected to CDMS conversion). Serum NfL levels were analyzed at baseline (Month-0)/Month-6/-12/-24. Only patients with NfL data at Month-0 and at least one other time-point (Month-6/-12/-24) were included. Treatment effect on NfL levels was compared using ANCOVA on log-transformed NfL data (M0 log-NfL concentration as covariate), and data presented for Month-6/-12. Least Square Mean (LSM; 95% confidence interval [CI]) NfL concentrations are reported unless stated otherwise. Percentages of patients who converted to McDonald 2005 MS by Month-24 were calculated by Kaplan-Meier curve.

Results Month-0: median NfL concentration of 26.1 pg/ml was used to define low/high NfL subgroups; mean (standard deviation) NfL levels were: scIFNβ-1a tiw, 45.7(62.4)pg/ml; scIFNβ-1a qw 54.6(106.2)pg/ml; placebo, 59.3(90.8)pg/ml. Month-6: LSM (95%CI) NfL concentration was reduced versus placebo (19.3[17.7-21.2]pg/ml;n=147) with scIFNβ-1a tiw (15.7[14.4-17.2]pg/ml;p=0.002;n=142) and scIFNβ-1a qw (15.7[14.4-17.2]pg/ml;p=0.001;n=154). Month-12: LSM (95%CI) NfL concentration was reduced versus placebo (16.9[15.2-18.8];n=117) with scIFNβ-1a tiw (14.0[12.7-15.5];p=0.015;n=131) but not scIFNβ-1a qw (15.1[13.6-16.6];p=0.125;n=138). In each treatment group, proportionally fewer patients in low NfL subgroup converted to McDonald MS by Month-24 (tiw:49.1%[37.9%-60.3%];qw:69.4%[59.0%-79.8%];placebo:80.2%[71.5%-88.8%]) than the high NfL subgroup (tiw:75.2%[65.6%-84.8%];qw:80.6%[72.2%-89.0%];placebo:91.2%[84.7%-97.6%]).

Conclusions Treatment with scIFNβ-1a tiw/qw reduced NfL levels in patients with FCDE as early as 6 months post-baseline. High baseline NfL levels were associated with earlier conversion to McDonald MS.

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)	The institution of Dr. Kappos has received research support from Bayer. The institution of Dr. Kappos has received research support from Biogen. The institution of Dr. Kappos has received research support from Genentech. The institution of Dr. Kappos has received research support from Genzyme. The institution of Dr. Kappos has received research support from Janssen. The institution of Dr. Kappos has received research support from Merck Serono. The institution of Dr. Kappos has received research support from Minoryx. The institution of Dr. Kappos has received research support from Novartis. The institution of Dr. Kappos has received research support from Roche. The institution of Dr. Kappos has received research support from Sanofi. The institution of Dr. Kappos has received research support from Santhera. The institution of Dr. Kappos has received research support from Swiss MS Society, Swiss National Research Foundation, European Union, Roche Research Foundation, Innosuisse. The institution of Dr. Kappos has received research support from Shionogi. The institution of Dr. Kappos has received research support from Japan Tobacco. The institution of Dr. Kappos has received research support from Auriga Vision AG. The institution of Dr. Kappos has received research support from EMD Serono. The institution of Dr. Kappos has received research support from Glaxo Smith Kline. The institution of Dr. Kappos has received research support from Wellmera AG. The institution of Dr. Kappos has received research support from Eli Lilly (Suisse) SA. The institution of Dr. Kappos has received research support from Bristol Myers Squibb. The institution of Dr. Kappos has received research support from Celltrion Inc. Dr. Kappos has received intellectual property interests from a discovery or technology relating to health care.
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.
Sanjeev Roy	Sanjeev Roy has received personal compensation for serving as an employee of Merck KgGA.
Delphine Issard, MD (Merck-Serono S.A)	Dr. Issard has nothing to disclose.

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