Pharmacokinetic considerations in the treatment of multiple sclerosis with interferon-β

Expert Opin Drug Metab Toxicol. 2015;11(12):1803-19. doi: 10.1517/17425255.2015.1094055. Epub 2015 Sep 30.

Abstract

Introduction: Interferon-β (IFNβ) is well established as a disease-modifying treatment for patients with multiple sclerosis. Several preparations of the biopharmaceutical are available differing in protein structure, formulation, dose as well as frequency and route of administration. Recently, a pegylated form of IFNβ has been marketed.

Areas covered: Following a PubMed database search, we provide an overview of what is presently known about the pharmacokinetics (PK) of IFNβ including its absorption, distribution, metabolism and elimination. Also, we discuss the association with clinically relevant issues such as treatment efficacy, adverse events and anti-drug antibodies.

Expert opinion: IFNβ has a bioavailability of ∼ 30% after subcutaneous or intramuscular administration, shows peak serum concentrations within several hours, has a half-life of < 1 day and is eliminated by a renal and hepatic pathway. PK parameters do not substantially differ between the types of IFNβ and routes of administration; only pegylation of IFNβ results in substantially increased and prolonged PK. Although no clinical dose-effect relationship could be established, there is an association of IFNβ dose with magnetic resonance imaging outcome parameters. Furthermore, there is an association of IFNβ serum levels with the occurrence of adverse events and anti-drug antibodies.

Keywords: flu-like symptoms; interferon-β; multiple sclerosis; neutralizing anti-drug antibodies; pegylation; pharmacokinetics; treatment efficacy.

Publication types

  • Review

MeSH terms

  • Animals
  • Biological Availability
  • Dose-Response Relationship, Drug
  • Half-Life
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / adverse effects
  • Immunologic Factors / pharmacokinetics*
  • Interferon-beta / administration & dosage
  • Interferon-beta / adverse effects
  • Interferon-beta / pharmacokinetics*
  • Magnetic Resonance Imaging
  • Multiple Sclerosis / drug therapy*
  • Tissue Distribution

Substances

  • Immunologic Factors
  • Interferon-beta