TY - JOUR T1 - Asthma prescribing according to Arg16Gly beta-2 genotype: a randomised trial in adolescents JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.04107-2020 VL - 58 IS - 2 SP - 2004107 AU - Tom Ruffles AU - Christina J. Jones AU - Colin Palmer AU - Steve Turner AU - Jonathan Grigg AU - Roger Tavendale AU - Fiona Hogarth AU - Petra Rauchhaus AU - Kristina Pilvinyte AU - Romanie Hannah AU - Helen Smith AU - Roberta Littleford AU - Brian Lipworth AU - Somnath Mukhopadhyay Y1 - 2021/08/01 UR - http://erj.ersjournals.com/content/58/2/2004107.abstract N2 - 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.Personalised prescribing in adolescents with asthma demonstrated that β2-adrenoreceptor genotype directed treatment results in a small but significant improvement in PAQLQ. β2-adrenoreceptor genotype guided treatment requires further investigation. https://bit.ly/3oDvP1N ER -