Mali Coray, PhD
,
Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland
Andrea Seitzinger, PhD
,
the healthcare business of Merck KGaA, Darmstadt, Germany
Sanjeev Roy, MD
,
Ares Trading S.A, Eysins, Switzerland
Mark S Freedman, MSc, MD
,
Department of Medicine and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada
Frederik Barkhof, MD, PhD
,
Department of Radiology and Nuclear Medicine, MS Center Amsterdam, Amsterdam, Netherlands, UCL Institute of Neurology, London, United Kingdom
Giancarlo Comi, MD
,
Casa di Cura Privata del Policlinico, Università Vita-Salute San Raffaele, Milan, Italy
Nicola De Stefano, MD, PhD
,
Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
Ludwig Kappos, PhD
,
Research Center for Clinical Neuroimmunology and Neuroscience, Basel, Switzerland, Research Center for Clinical Neuroimmunology and Neuroscience, University Hospital Basel, University of Basel, Basel, Switzerland
Jens Kuhle, MD, PhD
,
Neurology Departments of Head, Spine and Neuromedicine, Biomedical Engineering and Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland, Research Center for Clinical Neuroimmunology and Neuroscience, Basel, Switzerland
Matthias Mehling, PhD
,
Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland, Research Center for Clinical Neuroimmunology and Neuroscience, Basel, Switzerland, Neurology Departments of Head, Spine and Neuromedicine, Biomedical Engineering and Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland
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.
Objectives: 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).
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.
