BACKGROUND:Inhaled corticosteroids (ICSs) are considered the most effective anti-inflammatory therapy for asthma control and management; however, there is substantial treatment response variability. OBJECTIVE: We sought to identify genetic markers of ICS response by conducting the largest pharmacogenetic investigation to date in 2672 ICS-treated patients with asthma. METHODS: Genotyping and imputation was performed in fluticasone furoate (FF) or fluticasone propionate-treated patients with asthma from 3 phase IIB and 4 phase IIIA randomized, double-blind, placebo-controlled, parallel group, multicenter studies. The primary end point analyzed was change in trough FEV1 (ΔFEV1) from baseline to 8 to 12 weeks of treatment. RESULTS: More than 9.8 million common genetic variants (minor allele frequency ≥ 1%) were analyzed to test for association with ΔFEV1. No genetic variant met the prespecified threshold for statistical significance. CONCLUSIONS: This study provides no evidence to confirm previously reported associations between candidate genetic variants and ICS response (ΔFEV1) in patients with asthma. In addition, no variant satisfied the criterion for genome-wide significance in our study. Common genetic variants are therefore unlikely to prove useful as predictive biomarkers of ICS response in patients with asthma.
RCT Entities:
BACKGROUND: Inhaled corticosteroids (ICSs) are considered the most effective anti-inflammatory therapy for asthma control and management; however, there is substantial treatment response variability. OBJECTIVE: We sought to identify genetic markers of ICS response by conducting the largest pharmacogenetic investigation to date in 2672 ICS-treated patients with asthma. METHODS: Genotyping and imputation was performed in fluticasone furoate (FF) or fluticasone propionate-treated patients with asthma from 3 phase IIB and 4 phase IIIA randomized, double-blind, placebo-controlled, parallel group, multicenter studies. The primary end point analyzed was change in trough FEV1 (ΔFEV1) from baseline to 8 to 12 weeks of treatment. RESULTS: More than 9.8 million common genetic variants (minor allele frequency ≥ 1%) were analyzed to test for association with ΔFEV1. No genetic variant met the prespecified threshold for statistical significance. CONCLUSIONS: This study provides no evidence to confirm previously reported associations between candidate genetic variants and ICS response (ΔFEV1) in patients with asthma. In addition, no variant satisfied the criterion for genome-wide significance in our study. Common genetic variants are therefore unlikely to prove useful as predictive biomarkers of ICS response in patients with asthma.
Authors: Natalia Hernandez-Pacheco; Niloufar Farzan; Ben Francis; Leila Karimi; Katja Repnik; Susanne J Vijverberg; Patricia Soares; Maximilian Schieck; Mario Gorenjak; Erick Forno; Celeste Eng; Sam S Oh; Lina Pérez-Méndez; Vojko Berce; Roger Tavendale; Lesly-Anne Samedy; Scott Hunstman; Donglei Hu; Kelley Meade; Harold J Farber; Pedro C Avila; Denise Serebrisky; Shannon M Thyne; Emerita Brigino-Buenaventura; William Rodriguez-Cintron; Saunak Sen; Rajesh Kumar; Michael Lenoir; Jose R Rodriguez-Santana; Juan C Celedón; Somnath Mukhopadhyay; Uroš Potočnik; Munir Pirmohamed; Katia M Verhamme; Michael Kabesch; Colin N A Palmer; Daniel B Hawcutt; Carlos Flores; Anke H Maitland-van der Zee; Esteban G Burchard; Maria Pino-Yanes Journal: Clin Exp Allergy Date: 2019-02-15 Impact factor: 5.018
Authors: Mengyuan Kan; Avantika R Diwadkar; Haoyue Shuai; Jaehyun Joo; Alberta L Wang; Mei-Sing Ong; Joanne E Sordillo; Carlos Iribarren; Meng X Lu; Natalia Hernandez-Pacheco; Javier Perez-Garcia; Mario Gorenjak; Uroš Potočnik; Esteban G Burchard; Maria Pino-Yanes; Ann Chen Wu; Blanca E Himes Journal: J Allergy Clin Immunol Date: 2021-12-28 Impact factor: 14.290