title: A Mathematical Modeling Approach to Understanding the Effect of Anti-Interleukin Therapy on Eosinophils.
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.
authors.affiliation: Institute for Systems Biology, Moscow, Russia.
authors.forename: T
authors.initials: T
authors.lastname: Karelina
authors.affiliation: Institute for Systems Biology, Moscow, Russia.
authors.forename: V
authors.initials: V
authors.lastname: Voronova
authors.affiliation: Institute for Systems Biology, Moscow, Russia.
authors.forename: O
authors.initials: O
authors.lastname: Demin
authors.affiliation: Astrazeneca, Global Medicines Development, Gaithersburg, Maryland, USA.
authors.forename: G
authors.initials: G
authors.lastname: Colice
authors.affiliation: MedImmune LLC, Clinical Pharmacology, Drug Metabolism, and Pharmacokinetics, Mountain View, California, USA.
authors.forename: B M
authors.initials: BM
authors.lastname: Agoram
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D001249:Asthma / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D018793:Interleukin-13 / Q000037:antagonists & inhibitors*; D008954:Models, Biological; D012137:Respiratory System / Q000187:drug effects / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C578095:IL13 protein, human; D018793:Interleukin-13; C434107:mepolizumab; C574065:tralokinumab; C561806:lebrikizumab