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

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.