Abstract Details

Title Exploratory Analysis of Serum GDF-15 Levels in Patients Receiving Subcutaneous Interferon ß-1a in the REFLEX Trial

Topic Multiple Sclerosis

Presentation(s) P2 - Poster Session 2 (11:45 AM-12:45 PM)

Poster/Presentation
Number 12-007

Objective To investigate if serum levels of growth differentiation factor 15 (GDF-15) predict disease stability in patients with clinically isolated syndrome (CIS) treated with subcutaneous interferon beta-1a (sc IFNβ-1a).

Background sc IFNβ-1a is a well-established disease-modifying therapy for relapsing multiple sclerosis (MS), with an estimated cumulative exposure of 1,831,698 patient-years (to 30 April 2021). Serum levels of GDF-15, a cytokine with anti-inflammatory effects, are increased in patients with stable MS. However, no information is available concerning GDF-15 in patients treated with sc IFNβ-1a.

Design/Methods In the REFLEX study (NCT00404352), 480 CIS patients were randomized to treatment with sc IFNβ-1a 44mcg once-weekly (ow, n=162), 44mcg three-times-weekly (tiw, n=157), or placebo (n=161), for up to 24 months. Time from randomization to clinically definite MS (CDMS), defined by either a second demyelinating event or a sustained increase (≥1.5 points) in the EDSS score, was the primary endpoint. In this post hoc exploratory analysis, serum concentrations of GDF-15 were measured by ELISA at baseline and for up to 24 months, including the subgroup of CDMS non-converters vs converters. All analyses are descriptive.

Results Whilst median serum GDF-15 levels showed little change between baseline and Month 24 for sc IFNβ-1a 44mcg ow and placebo, they increased in the 44mcg tiw group following treatment start (baseline, 323pg/mL [n=157]; Month 6, 391pg/mL [n=135]; Month 24, 391pg/mL [n=114]). This increase was apparent irrespective of baseline GDF-15 levels. Under treatment with sc IFNβ-1a 44mcg tiw, CDMS non-converters had persistently higher levels of serum GDF-15 vs CDMS converters.

Conclusions In CIS patients, GDF-15 levels increased during treatment with sc IFNβ-1a 44mcg tiw. The more pronounced increase of GDF-15 levels in CDMS non-converters treated with sc IFNβ-1a 44mcg tiw indicates that levels of this anti-inflammatory cytokine may serve as a biomarker of treatment response and stable disease under such therapy in early MS.

Authors/Disclosures
Elisabetta Verdun Di Cantogno, MD (Merck Serono Int, SA) PRESENTER	Dr. Verdun Di Cantogno has received personal compensation for serving as an employee of EMD Serono Research & Development Institute, Inc., Billerica, MA, USA. Dr. Verdun Di Cantogno has stock in EMD Serono Research & Development Institute, Inc., Billerica, MA, USA.
Mali C. Coray (University of Basel)	Ms. Coray has received research support from Swiss National Science Foundation (SNSF).
	No disclosure on file
Sanjeev Roy	Sanjeev Roy has received personal compensation for serving as an employee of Merck KgGA.
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.
Frederik Barkhof, MD, PhD (Image Analysis Center)	Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Frederik Barkhof has received personal compensation in the range of $0-$499 for serving as a Consultant for Biogen. Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Combinostics. Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving as a Consultant for IXICO. Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EISAI.
Giancarlo Comi, MD (University Vita-Salute)	Dr. Comi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Janssen. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Aspen Healthcare. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Sanofi. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Rewind.
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.
Jens Kuhle, MD	Dr. Kuhle has nothing to disclose.
Matthias Mehling, MD (Neurology Clinic University Hospital Basel/Switzerland)	The institution of Dr. Mehling has received research support from Swiss National Science Foundation. The institution of Dr. Mehling has received research support from Roche. The institution of Dr. Mehling has received research support from Merck.

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