[Pharmacokinetic variability of therapeutic antibodies]

Med Sci (Paris). 2019 Dec;35(12):1130-1136. doi: 10.1051/medsci/2019210. Epub 2020 Jan 6.
[Article in French]

Abstract

Therapeutic antibodies have been increasingly used for the treatment of various diseases, including cancers and chronic inflammatory diseases. The pharmacokinetic interindividual variability of mAbs is large and influences, at least in part, the clinical response to antibody treatment. This variability is explained by a number of individual sources of variability, which are reviewed here. Some of them are major because they are frequently reported to greatly influence the interindividual variability; notably, increased body size, the presence of anti-drug antibodies, and high antigen mass are associated with decreased antibody concentrations. Other individual sources of variability are of less critical importance. They include sex, age, co-treatments, or genetic polymorphisms of IgG Fc receptors (FcgRs). The interindividual variability of antibody pharmacokinetics should be soundly described in order to design optimal dosing strategy.

Title: Variabilité pharmacocinétique des anticorps thérapeutiques.

Abstract: Les anticorps thérapeutiques sont de plus en plus utilisés dans le traitement de différentes pathologies, dont les cancers et les maladies inflammatoires chroniques. La variabilité pharmacocinétique interindividuelle des anticorps est grande et influence la réponse clinique. Certaines caractéristiques de l’individu jouent un rôle majeur car elles modifient fortement cette pharmacocinétique, telles les dimensions corporelles, l’immunisation contre les anticorps thérapeutiques utilisés ou la masse antigénique. D’autres jouent un rôle mineur, comme l’âge, le sexe ou des polymorphismes génétiques. Cette variabilité doit être décrite avec soin pour déterminer le schéma posologique optimal.

Publication types

  • Review

MeSH terms

  • Age Factors
  • Antibodies, Monoclonal / pharmacokinetics*
  • Antibodies, Monoclonal / therapeutic use
  • Biomarkers, Pharmacological / analysis
  • Comorbidity
  • Dose-Response Relationship, Immunologic
  • Female
  • Humans
  • Individuality*
  • Male
  • Pharmacogenomic Testing
  • Polymorphism, Genetic / physiology
  • Precision Medicine / methods
  • Sex Factors

Substances

  • Antibodies, Monoclonal
  • Biomarkers, Pharmacological