A Mathematical Modeling Approach to Understanding the Effect of Anti-Interleukin Therapy on Eosinophils

CPT Pharmacometrics Syst Pharmacol. 2016 Nov;5(11):608-616. doi: 10.1002/psp4.12129.

Abstract

Emerging T-helper type 2 (Th2 ) cytokine-based asthma therapies, such as tralokinumab, lebrikizumab (anti-interleukin (IL)-13), and mepolizumab (anti-IL-5), have shown differences in their blood eosinophil (EOS) response. To better understand these effects, we developed a mathematical model of EOS dynamics. For the anti-IL-13 therapies, lebrikizumab and tralokinumab, the model predicted an increase of 30% and 10% in total and activated EOS in the blood, respectively, and a decrease in the total and activated EOS in the airways. The model predicted a rapid decrease in total and activated EOS levels in blood and airways for the anti-IL-5 therapy mepolizumab. All model-based predictions were consistent with published clinical observations. The modeling approach provided insights into EOS response after treatment with Th2 -targeted therapies, and supports the hypothesis that an increase in blood EOS after anti-IL-13 therapy is part of the pharmacological action of these therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Asthma / blood
  • Asthma / drug therapy*
  • Asthma / immunology
  • Eosinophils / drug effects*
  • Eosinophils / immunology
  • Humans
  • Interleukin-13 / antagonists & inhibitors*
  • Models, Biological*
  • Respiratory System / drug effects
  • Respiratory System / immunology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Interleukin-13
  • interleukin-13, human
  • tralokinumab
  • mepolizumab
  • lebrikizumab