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Asthma prescribing according to Arg16Gly beta-2 genotype: a randomised trial in adolescents

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posted on 2023-06-09, 22:39 authored by Thomas RufflesThomas Ruffles, Christina J Jones, Colin Palmer, Steve Turner, Jonathan Grigg, Roger Tavendale, Fiona Hogarth, Petra Rauchhaus, Kristina Pilvinyte, Romanie Hannah, Helen Smith, Roberta Littleford, Brian Lipworth, Somnath MukhopadhyaySomnath Mukhopadhyay
Introduction The A allele of rs1042713 (Arg16 amino acid) in the beta-2 (ß2) adrenoreceptor is associated with poor response to long-acting ß2-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 ß2-adrenoceptor genotype directed therapy in younger and more severe childhood asthma warrants further exploration.

History

Publication status

  • Published

File Version

  • Accepted version

Journal

European Respiratory Journal

ISSN

0903-1936

Publisher

European Respiratory Society

Department affiliated with

  • Clinical and Experimental Medicine Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2021-01-08

First Open Access (FOA) Date

2022-01-22

First Compliant Deposit (FCD) Date

2021-01-06

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