Mechanisms of allergy and clinical immunologyIL-4 receptor polymorphisms predict reduction in asthma exacerbations during response to an anti–IL-4 receptor α antagonist
Section snippets
Clinical trial population
A pharmacogenetic analysis was performed in a phase 2b clinical trial of pitrakinra, an IL-4Rα antagonist. In this trial 534 participants with moderate-to-severe asthma from the intent-to-treat population were enrolled in a 12-week randomized, placebo-controlled, multicenter (sites in the United States and Europe), double-blind, dose-ranging study (1, 3, or 10 mg twice daily) to test the safety and efficacy of pitrakinra. Subjects were evaluated for the primary end point of incidence of asthma
Demographics
Demographic and baseline clinical characteristics, including lung function, total serum IgE levels, and fraction of exhaled nitric oxide (Feno) levels, of participants were similar for subjects in the overall intent-to-treat trial population (n = 534) and the genotyped non-Hispanic white subjects (n = 407) analyzed in this study (Table I).
Asthma exacerbations
In this pitrakinra 2b clinical trial the frequency of asthma exacerbations was 19.9% overall, and there were no significant differences in exacerbations in
Discussion
This is the first large pharmacogenetic analysis of the TH2-related IL-4/IL-13 inflammatory receptor in subjects with moderate-to-severe asthma. In this relatively short (12-week) trial, LABAs were tapered 4 weeks after initiation of blinded IL-4Rα antagonist or placebo treatment, and inhaled corticosteroids were tapered and withdrawn subsequently. Although there was no overall significant difference between active IL-4Rα therapy and placebo,15, 16 therapeutic efficacy was observed by IL4RA
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Supported by Aerovance, Bayer Healthcare, and the National Institute of Heart, Lung, and Blood grants HL065899, HL101487, and HL089992.
Disclosure of potential conflict of interest: R. E. Slager has received grants from the National Institutes of Health (NIH) and research support from Aerovance. B. A. Otulana and Y. P. Yen are employees of Aerovance. G. A. Hawkins has received research support from Aerovance. S. P. Peters has received research support from the NIH. S. E. Wenzel has consulted for Genentech, and has received research support from Aerovance, GlaxoSmithKline, and Sanofi-Aventis. D. A. Meyers and E. R. Bleecker have consulted for and received research support from Aerovance.