Pharmacogenomic Response of Inhaled Corticosteroids for the Treatment of Asthma: Considerations for Therapy

Abstract

There is a large interindividual variability in response to ICSs in asthma. About 70% of the variance in ICS response is likely due at least partially to genetically determined characteristics of target genes. In this article, we examine the effects on the ICS response of gene variations in the corticosteroid pathway, and in the pharmacokinetics of corticosteroids, and also those outside the corticosteroid pathway, which have the potential to influence corticosteroid activity. Although the available evidence indicates that responses to ICSs in asthma are influenced by different genetic variants, there are still deep uncertainties as to whether a real association between these genetic variants and corticosteroid response could also possibly exist because there are difficulties in reproducing pharmacogenetic findings. This explains at least partly the insufficient use of pharmacogenomic data when treating asthmatic patients, which creates a real limitation to the proper use of ICSs in an era of precision medicine that links the right patient to the right treatment. Knowing and dealing with the genetic factors that influence the therapeutic ICS response is a fundamental condition for prescribing the right dose of ICS to the right patient at the right time.

Keywords: asthma; gene polymorphisms; genome-wide association studies; inhaled corticosteroids; precision medicine.