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

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

Author information

1
Institute for Systems Biology, Moscow, Russia.
2
Astrazeneca, Global Medicines Development, Gaithersburg, Maryland, USA.
3
MedImmune LLC, Clinical Pharmacology, Drug Metabolism, and Pharmacokinetics, Mountain View, California, USA.

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.

PMID:
27885827
PMCID:
PMC5192997
DOI:
10.1002/psp4.12129
[Indexed for MEDLINE]
Free PMC Article

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