Pharmacodynamic biomarkers of long-term interferon beta-1a therapy in REFLEX and REFLEXION

J Neuroimmunol. 2021 Nov 15:360:577715. doi: 10.1016/j.jneuroim.2021.577715. Epub 2021 Sep 9.

Abstract

This post-hoc analysis evaluated candidate biomarkers of long-term efficacy of subcutaneous interferon beta-1a (sc IFN β-1a) in REFLEX/REFLEXION studies of clinically isolated syndrome. Samples from 507 REFLEX and 287 REFLEXION study participants were analyzed. All investigated biomarkers were significantly upregulated 1.5-4-fold in response to sc IFN β-1a treatment versus baseline (p ≤ 0.008). The validity of MX1, 2'5'OAS, and IL-1RA as biomarkers of response to sc IFN β-1a was confirmed in this large patient cohort, with biomarkers consistently upregulated in a dose-dependent manner. Neopterin, TRAIL, and IP-10 were confirmed as biomarkers associated with long-term sc IFN β-1a treatment efficacy over 5 years.

Keywords: Biomarkers; Interferon beta; Multiple sclerosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / biosynthesis
  • 2',5'-Oligoadenylate Synthetase / blood
  • 2',5'-Oligoadenylate Synthetase / genetics
  • Biomarkers
  • Chemokine CXCL10 / biosynthesis
  • Chemokine CXCL10 / blood
  • Chemokine CXCL10 / genetics
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Follow-Up Studies
  • Humans
  • Injections, Subcutaneous
  • Interferon beta-1a / administration & dosage
  • Interferon beta-1a / pharmacokinetics
  • Interferon beta-1a / therapeutic use*
  • Interleukin 1 Receptor Antagonist Protein / biosynthesis
  • Interleukin 1 Receptor Antagonist Protein / blood
  • Interleukin 1 Receptor Antagonist Protein / genetics
  • Multicenter Studies as Topic
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / drug therapy*
  • Myxovirus Resistance Proteins / biosynthesis
  • Myxovirus Resistance Proteins / blood
  • Myxovirus Resistance Proteins / genetics
  • Neopterin / biosynthesis
  • Neopterin / blood
  • Neopterin / genetics
  • Randomized Controlled Trials as Topic / statistics & numerical data
  • TNF-Related Apoptosis-Inducing Ligand / biosynthesis
  • TNF-Related Apoptosis-Inducing Ligand / blood
  • TNF-Related Apoptosis-Inducing Ligand / genetics
  • Up-Regulation

Substances

  • Biomarkers
  • CXCL10 protein, human
  • Chemokine CXCL10
  • Interleukin 1 Receptor Antagonist Protein
  • MX1 protein, human
  • Myxovirus Resistance Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Neopterin
  • 2',5'-Oligoadenylate Synthetase
  • Interferon beta-1a