A Mathematical Modeling Approach to Understanding the Effect of Anti‐Interleukin Therapy on Eosinophils. (November 2016)

• Record Type: Journal Article
• Authors: Karelina, T; Voronova, V; Demin, O; Colice, G; Agoram, BM
• Is Part Of: CPT: pharmacometrics & systems pharmacology. Volume 5:Number 11(2016:Nov.)
• Page Start: 608
• Page End: 616
• Publication Date: 2016-11
• Subjects: Pharmacokinetics -- Periodicals; Pharmacology -- Periodicals; Pharmacokinetics; Periodicals; 615.05
• DOI: 10.1002/psp4.12129
• Languages: English
• ISSNs: 2163-8306

Abstract

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.