Pharmacogenomics of long-acting β₂-agonists

Abstract

Introduction: Long-acting β₂-agonists are an effective class of drugs, when combined with inhaled corticosteroids, for reducing symptoms and exacerbations in patients with asthma that is not adequately controlled by inhaled corticosteroids alone. However, because this class of drugs has been associated with severe adverse events, including hospitalization and death in small numbers of patients, efforts to identify a pharmacogenetic profile for patients at risk has been diligently investigated.

Areas covered: The PubMed search engine of the National Library of Medicine was used to identify English-language and non-English language articles published from 1947 to March 2015 pertinent to asthma, pharmacogenomics, and long-acting β₂-agonists. Keywords and topics included: asthma, asthma control, long-acting β₂-agonists, salmeterol, formoterol, pharmacogenetics, and pharmacogenomics. This strategy was also used for the Cochrane Library Database and CINAHL. Reference types were randomized controlled trials, reviews, and editorials. Additional publications were culled from reference lists. The publications were reviewed by the authors and those most relevant were used to support the topics covered in this review.

Expert opinion: Children, who carry the ADRB2 Arg16Arg genotype, may be at greater risk than adults for severe adverse events. Rare ADRB2 variants appear to provide better clues for identifying the at-risk population of asthmatics.

Keywords:

• asthma
• children
• long-acting β2-agonists
• pharmacogenomic
• rare variants
• serious adverse events

Declaration of interest

The authors are supported by funding from Nemours Biomedical Research. K Blake is a co-investigator and J Lima is a principal investigator with the American Lung Association Airways Clinical Research Centers Network funded by the American Lung Association and AsthmaNet funded by the National Institutes of Health. These networks have ongoing trials in which sponsors of long-acting β₂-agonists are contributing funding or drugs. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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