No evidence of large genetic effects on steroid response in asthma patients.

Abstract

Inhaled corticosteroids (ICSs) are considered the most effective anti-inflammatory therapy for asthma control and management; however, there is substantial treatment response variability. We sought to identify genetic markers of ICS response by conducting the largest pharmacogenetic investigation to date in 2672 ICS-treated patients with asthma. 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. 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. 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.