Abstract
Introduction The A allele of rs1042713 (Arg16 amino acid) in the beta-2 (β2) adrenoreceptor is associated with poor response to long-acting β2-agonist (LABA) in young people with asthma. Our aim was to assess whether the prescribing of second line controller with LABA or a leukotriene receptor antagonist (LTRA) according to Arg16Gly genotype would result in improvements in pediatric asthma-related quality of life questionnaire (PAQLQ).
Methods We performed a pragmatic randomised controlled trial (RCT) via a primary care clinical research network covering England and Scotland. We enrolled participants aged 12–18 years with asthma taking inhaled corticosteroids. A total of 241 participants (mean (sd) age 14.7 years (1.91)) were randomised (1:1) to receive personalised care (genotype directed prescribing) or standard guideline care. Following 4-week run-in participants were followed for 12-months. The primary outcome measure was change in PAQLQ. Asthma control, asthma exacerbation frequency and healthcare utilisation were secondary outcomes.
Results Genotype directed prescribing resulted in an improvement in PAQLQ compared to standard care 0.16, (95%CI 0.00–0.31; p=0.049), although this improvement was below the pre-determined clinical threshold of 0.25. The AA genotype was associated with a larger improvement in PAQLQ with personalised versus standard care 0.42, (95%CI 0.02–0.81; p=0.041).
Conclusion This is the first RCT demonstrating that genotype driven asthma prescribing is associated with a significant improvement in a clinical outcome compared to standard care. Adolescents with the AA homozygous genotype benefited most. The potential role of such β2-adrenoceptor genotype directed therapy in younger and more severe childhood asthma warrants further exploration.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. Ruffles has nothing to disclose.
Conflict of interest: Dr. Jones reports and The research was funded by children's charity Action Medical Research.
Conflict of interest: Dr. Palmer has nothing to disclose.
Conflict of interest: Dr. Turner reports and The research was funded by children's charity Action Medical Research.
Conflict of interest: Dr. Grigg reports personal fees from AstraZeneca, personal fees from GSK, personal fees from Medimmune, personal fees from BV Pharma, during the conduct of the study;.
Conflict of interest: Dr. Tavendale has nothing to disclose.
Conflict of interest: Dr. Hogarth reports grants from University of Sussex, during the conduct of the study;.
Conflict of interest: Ms. Rauchhaus has nothing to disclose.
Conflict of interest: Ms Pilvinyte has nothing to disclose.
Conflict of interest: Dr. Hannah has nothing to disclose.
Conflict of interest: Dr. SMITH has nothing to disclose.
Conflict of interest: Dr. Littleford reports grants from The Henry Smith Charity, grants from Action Medical Research, during the conduct of the study.
Conflict of interest: Dr. Lipworth reports other from GSK, grants, personal fees and non-financial support from AstraZeneca, grants, personal fees and non-financial support from Chiesi, personal fees from Novartis, grants, personal fees and non-financial support from Boerhinger Inhgelheim, personal fees from Dr Reddys, personal fees from Sandoz, personal fees from Cipla, personal fees from Glenmark, grants, personal fees and non-financial support from Teva, during the conduct of the study; personal fees from Lupin, grants and personal fees from Sanofi Regeneron, personal fees from Vectura, outside the submitted work; and Son of BJL is employee of AstraZeneca.
Conflict of interest: Dr. Mukhopadhyay has nothing to disclose.
- Received November 6, 2020.
- Accepted January 1, 2021.
- ©The authors 2021. For reproduction rights and permissions contact permissions{at}ersnet.org
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