https://orcid.org/0000-0003-4895-9707
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.
Author Contributions
All authors made substantial contributions to conception of the article; took part in drafting the article or revising it critically for important intellectual content; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.
Disclosure
Mario Cazzola has participated as a faculty member, and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, Lallemand, Mundipharma, Novartis, Pfizer, Recipharm, Verona Pharma, and Zambon, and is or has been a consultant to ABC Farmaceutici, AstraZeneca, Chiesi Farmaceutici, Recipharm, Lallemand, Novartis, Ockham Biotech, Verona Pharma, and Zambon. His department was funded by Almirall, Boehringer Ingelheim, Novartis, and Zambon.
Paola Rogliani participated as a lecturer and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, Mundipharma, Novartis, and Recipharm. Her department was funded by Almirall, Boehringer Ingelheim, Chiesi Farmaceutici, Novartis, and Zambon.
Luigino Calzetta has participated as an advisor in scientific meetings under the sponsorship of Boehringer Ingelheim and Novartis, received non-financial support from AstraZeneca, a research grant partially funded by Chiesi Farmaceutici, Boehringer Ingelheim, Novartis, and Almirall, and is or has been a consultant to ABC Farmaceutici, Recipharm, Zambon, Verona Pharma, and Ockham Biotech.
Maria Gabriella Matera has participated as a lecturer and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, and Novartis, and has been a consultant to ABC Farmaceutici, and Chiesi Farmaceutici. Her department was funded by Novartis.
The authors have no other relevant affiliations or financial involvement with any organization or entity with financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.