IL-4 receptor alpha polymorphisms are predictors of a pharmacogenetic response to a novel IL-4/IL-13 antagonist.

摘要

Evidence from genomic research, in vitro cell signaling, and animal studies strongly implicates the IL-4/IL-13 pathways in the pathogenesis of allergic asthma.1"7 However, there are limited data on pharmacologic modulation of these pathways. We performed a descriptive pharmacogenetic analysis using data from an early phase II mechanistic trial of the drug pitrakinra, a novel IL-4/IL-13 dual antagonist, in patients with allergic asthma (Clinicaltrials.gov identifier NCT00535431).8 Pitrakinra is similar to the native IL-4 molecule, although specifically designed with 2 ammo acid changes (R121D/Y124D), rendering it an effective competitive antagonist of IL-4 receptor a (IL-4Ra).8 Pitrakinra reduces late-phase responses to inhaled antigen based on phase II clinical studies to date,8 and genomic DNA samples were obtained from 29 participants in this clinical trial.