Specific genetic alterations in children and teens with asthma may identify those who will not benefit from treatment with the long-acting β2-adrenergic receptor agonist (LABA) salmeterol, a researcher reported.
For the study, 241 children and teens (age 12-18) with asthma taking inhaled corticosteroids were randomly assigned (1:1) to receive personalized care (prescribing by rs1042713 genotype) or standard care based on British Thoracic Society asthma treatment guidelines, according to Somnath Mukhopadhyay, MD, PhD, of Brighton & Sussex Medical School in England.
The children, recruited from general practitioners’ offices across the U.K., were followed for 12 months, and the primary outcome was change in quality of life (QoL), as measured by the Asthma Quality of Life Questionnaire (AQLQ). Secondary outcomes included asthma control, exacerbation frequency, and asthma-related healthcare utilization, Mukhopadhyay and colleagues stated in a presentation at the virtual European Respiratory Society (ERS) International Congress.
In the personalized medicine group, children found to have the rs1042713 genotype were treated with the leukotriene inhibitor montelukast as an add-on to inhaled steroids instead of salmeterol.
While the QoL significantly improved in the personalized medicine group versus the standard-of-care group (0.16, 95% CI 0.001-0.31, P=0.049), this difference was below the clinical threshold of 0.25.
However, in a sub-analysis involving children with two copies of the altered β2 receptor gene, a 0.42 improvement in AQLQ score was seen.
Findings from this first study to examine genetic differences in children and adolescents with asthma as a predictor of treatment response could lead to personalized medicine based on those differences, according to the auth0rs.
Mukhopadhyay told MedPage Today that in earlier work over the course of a decade, he and his colleagues identified specific alterations in the β2 receptor gene associated with poor response to the add-on asthma treatment salmeterol in children.
The research identified the A allele of rs1042713 (Arg16 amino acid) as a predictor of poor LABA response, leading the researchers to hypothesize that targeted treatment based on this genetic profile could improve asthma control in many children.
“Salmeterol works well as an add-on to inhaled steroid therapy in about 65% to 70% of children, but it doesn’t work in the rest,” Mukhopadhyay said. “We conducted this pragmatic study to determine if this personalized medicine approach would be beneficial.”
Mukhopadhyay said the results are promising “because they show, for the first time, that it could be beneficial to test for certain genetic differences in children with asthma” and to choose add-on medications based on these differences.
He added that the genetic testing costs about $15 and could be made available for use in the general practice setting if the interest is there.
He said the modest effect on QoL outcomes in the study could be due to the fact that asthma control in the cohort was generally good, with only a few children experiencing serious symptoms during the year-long follow-up.
“I think a larger trial is warranted, possibly in sicker children who are visiting hospitals frequently and missing a lot of school,” he said. “I would also like to study a younger age group, because there is evidence that younger children are more effected. We might see a bigger treatment effect in children who are 5- to 11-years old.”
Co-author Tom Ruffles, a PhD candidate at Brighton & Sussex Medical School, agreed.
“Further large trials are required with a focus on those children with poorer asthma control to help us determine the potential role for personalized care among children with asthma,” Ruffles said during an earlier press briefing.
ERS President Thierry Troosters, PT, PhD, of the University of Leuven in Belgium, said during the press briefing that, even though the study results were smaller than expected, “this is a major step forward in being able to identify a genetic parameter that may guide treatment in the future. Particularly when we are talking about children who may need treatment for a long time, this is a really important finding. I hope you [the authors] can follow-up on it.”
Disclosures
The study was funded by The Henry Smith Charity and Action Medical Research.
Mukhopadhyay and Ruffles disclosed no relevant relationships with industry.