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A $25 genetic test could inform physicians on optimal controller therapy for children and adolescents with asthma.
Genotype-based asthma controller prescribing may provide a significant improvement on primary clinical care of young patients than standard care, according to new study findings.
In new data presented virtually during the European Respiratory Society (ERS) 2020 International Congress this week, a team of UK-based investigators found that genetic-based treatment guidance could greatly influence quality-of-life metrics among pediatric and adolescent patients with asthma.
Investigators, led by Somnath Mukhopadhyay, MD, PhD, Pediatrics Chair at the Brighton and Sussex Medical School in England, conducted a randomized, controlled trial with participants recruited through primary care research networks. They sought to compare the clinical benefit of treating patients based on differences in the A allele of rs1042713 (Arg16 amino acid)—a genotype associated with poor response to standard long-acting beta-2 agonist (LABA) therapy among young asthmatics.
Previous assessments, Mukhopadhyay and colleagues wrote, show the majority of children with asthma benefit from standard LABA therapy including salmeterol plus inhaled corticosteroid (ICS). But about 1 in 7 children carry the different genotype which could result in such treatment regimen actually exacerbating symptoms.
Investigators randomized 241 participants aged 12-18 years old 1:1 to either rs1042713 genotype-personalized therapy (n = 121) or standard therapy (n = 120). Personalized therapy included montelukast, while standard therapy included LABA plus ICS.
Follow-up ran for 12 months, with an investigated primary outcome of measured change in Asthma Quality of Life Questionnaire (AQLQ) scoring—which gauges symptoms and their effect on everyday life on a 1-7 numerical scale. The team also assessed patients for metrics in asthma control, exacerbation frequency, and healthcare utilization.
At 12 months, genotype-based treatment was associated with a 0.16-point improvement (95% CI, 0.00-0.31; P = .049) in AQLQ versus standard therapy . Among pediatric patients with 2 copies of the altered beta-2 receptor gene, however, quality of life score was 0.42 improved versus standard care (95% CI, 0.02-0.81; P =.041).
In a statement accompanying the findings, Mukhopadhyay called the results promising, showing a pathway to testing genetic differences in asthmatic children—an approximate cost of $25 USD per patient—prior to prescribing therapy.
“In this study, we saw only a modest effect, but this may be partly because the children’s asthma was generally very well controlled and only a few children experienced any serious symptoms during the 12-month period,” he said. “Larger trials, with a focus on those with poorer asthma control, may help us determine the true benefit for children of prescribing in this way.”
Investigators concluded by stating their study was the first to demonstrate genotype-based asthma controller therapy prescribing could significantly improve clinical outcomes in pediatric patients versus standard care—with those homozygous for Arg16 (A/A) benefitting the most.
“The potential role of rs1042713 genotype directed therapy in younger and more severe children’s asthma requires further exploration,” they wrote.
The study, “Effect of controller prescribing according to rs1042713 genotype on asthma related quality of life in young people (PACT): a randomized controlled trial,” was presented at ERS 2020.