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

Eur Respir J. 2021 Aug 19;58(2):2004107. doi: 10.1183/13993003.04107-2020. Print 2021 Aug.

Abstract

Introduction: The A allele of rs1042713 (Arg16 amino acid) in the 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 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 β2-adrenoceptor genotype directed therapy in younger and more severe childhood asthma warrants further exploration.

Trial registration: ClinicalTrials.gov NCT02758873.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adrenal Cortex Hormones / therapeutic use
  • Alleles
  • Anti-Asthmatic Agents* / therapeutic use
  • Asthma* / drug therapy
  • Asthma* / genetics
  • Child
  • Drug Therapy, Combination
  • England
  • Genotype
  • Humans

Substances

  • Adrenal Cortex Hormones
  • Anti-Asthmatic Agents

Associated data

  • ClinicalTrials.gov/NCT02758873