TY - JOUR
T1 - Asthma prescribing according to Arg16Gly beta-2 genotype
T2 - a randomised trial in adolescents
AU - Ruffles, Tom
AU - Jones, Christina J.
AU - Palmer, Colin
AU - Turner, Steve
AU - Grigg, Jonathan
AU - Tavendale, Roger
AU - Hogarth, Fiona
AU - Rauchhaus, Petra
AU - Pilvinyte, Kristina
AU - Hannah, Romanie
AU - Smith, Helen
AU - Littleford, Roberta
AU - Lipworth, Brian
AU - Mukhopadhyay, Somnath
N1 - Funding Information:
Participants were principally recruited through primary care via the Clinical Research Network across England and Scotland as well as the patient databases BREATHE and PAGES. Informed consent and assent were obtained online or by telephone with follow-up written consent. The study followed the Children’s Research Network standard operating procedures, Health Research Agency guidelines and the Nuffield Council on Bioethics report [16] in obtaining informed consent. Participants aged 12–18 years consented independently, while parental consent was sought in addition for those aged ⩽15 years. The trial was sponsored by the University of Sussex (approval December 2014) and ethical approval was obtained from the East of Scotland Research Ethics Committee (15/ES/0007; approval March 2015). The trial was registered on the UK Clinical Research Network website with details made available to the public before the recruitment of the first participant. This trial is registered with ClinicalTrials.gov NCT02758873.
Funding Information:
Support statement: The study was funded by The Henry Smith Charity and Action Medical Research (grant number GN2203). The funders had no role in the design and conduct of the study; collection, management, analysis an interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Funding information for this article has been deposited with the Crossref Funder Registry.
Publisher Copyright:
Copyright © The authors 2021.
PY - 2021/8/1
Y1 - 2021/8/1
N2 - Introduction: The A allele of rs1042713 (Arg16 amino acid) in the β 2-adrenoreceptor is associated with poor response to long-acting β 2-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 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. 241 participants (mean±SD age 14.7±1.91 years) were randomised (1:1) to receive personalised care (genotype directed prescribing) or standard guideline care. Following a 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 β 2-adrenoceptor genotype directed therapy in younger and more severe childhood asthma warrants further exploration.
AB - Introduction: The A allele of rs1042713 (Arg16 amino acid) in the β 2-adrenoreceptor is associated with poor response to long-acting β 2-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 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. 241 participants (mean±SD age 14.7±1.91 years) were randomised (1:1) to receive personalised care (genotype directed prescribing) or standard guideline care. Following a 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 β 2-adrenoceptor genotype directed therapy in younger and more severe childhood asthma warrants further exploration.
KW - genotype
KW - beta-2 gene polymorphysms
KW - paediatric asthma
KW - asthma clinical trials
KW - Asthma Quality of Life
UR - http://www.scopus.com/inward/record.url?scp=85103226095&partnerID=8YFLogxK
U2 - 10.1183/13993003.04107-2020
DO - 10.1183/13993003.04107-2020
M3 - Article
C2 - 33479111
SN - 0903-1936
VL - 58
JO - European Respiratory Journal
JF - European Respiratory Journal
IS - 2
M1 - 2004107
ER -
