IL-4 receptor polymorphisms predict reduction in asthma exacerbations during response to an anti–IL-4 receptor α antagonist Rebecca E. Slager, PhD, MS,

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Presentation transcript:

IL-4 receptor polymorphisms predict reduction in asthma exacerbations during response to an anti–IL-4 receptor α antagonist Rebecca E. Slager, PhD, MS, Babatunde A. Otulana, MD, Gregory A. Hawkins, PhD, Yu Ping Yen, PhD, Stephen P. Peters, MD, PhD, Sally E. Wenzel, MD, Deborah A. Meyers, PhD, Eugene R. Bleecker, MD Journal of Allergy and Clinical Immunology Volume 130, Issue 2, Pages 516-522.e4 (August 2012) DOI: 10.1016/j.jaci.2012.03.030 Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Exacerbations by treatment assignment stratified by IL4RA SNP genotype. There was a significant dose-response trend for treatment response to exacerbations in subjects homozygous for the rs8832GG genotype (A) and the GG genotype in the correlated SNP rs1029489 (B). Journal of Allergy and Clinical Immunology 2012 130, 516-522.e4DOI: (10.1016/j.jaci.2012.03.030) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 IL4RA variants associated with exacerbations. Seven IL4RA SNPs were significantly associated with asthma exacerbations by genotype in participants randomized to 3- and 10-mg doses of pitrakinra. The dashed line indicates overall exacerbation frequency (19.7%) in genotyped non-Hispanic white subjects. Journal of Allergy and Clinical Immunology 2012 130, 516-522.e4DOI: (10.1016/j.jaci.2012.03.030) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Kaplan-Meier plot for time to exacerbation by treatment assignment for subjects with the rs8832GG genotype. On study day 28, LABAs were withdrawn, and inhaled corticosteroids were stepped down on study days 42 and 56 and stopped completely on day 70. There was a significant difference in time to exacerbation by survival time analysis for subjects with the rs8832GG genotype randomized to 10 mg of pitrakinra compared with placebo. P values are from log-rank tests. Journal of Allergy and Clinical Immunology 2012 130, 516-522.e4DOI: (10.1016/j.jaci.2012.03.030) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 IL4RA polymorphisms predict change in nighttime awakenings caused by asthma. There was a significant dose-response trend for change in nighttime awakenings by treatment assignment (placebo/1 mg/3 mg/10 mg) observed for subjects with the common rs8832GG genotype (A) and participants with the common rs3024622CC genotype (B). There was no significant trend for participants with the minor allele in these SNPs. CFB, Change from baseline. Journal of Allergy and Clinical Immunology 2012 130, 516-522.e4DOI: (10.1016/j.jaci.2012.03.030) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Map of IL4RA variants genotyped in this study and the linkage disequilibrium (r2) plot (generated in Haploview version 4.2) for genotyped non-Hispanic white subjects. Significant pharmacogenetic associations with asthma exacerbations are noted. Journal of Allergy and Clinical Immunology 2012 130, 516-522.e4DOI: (10.1016/j.jaci.2012.03.030) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions