Common gene variant reduces effectiveness of pediatric asthma drug

Children with a variant in the SERPINE1 gene – which is found in 60% of the population – may be less responsive to mepolizumab, a drug used to treat asthma flares, according to a study published in the Journal of Allergy and Clinical Immunology.

The study revealed that this genetic variant produces more protein (PAI1) during a viral illness, which leads to more scarring of the airway and lower antiviral response. When combined with the asthma drug, more inflammatory pathways that damage the airway are stimulated, whereas these changes do not occur when the drug is given to patients without the SERPINE1 variant.

We know from previous studies that children with this genetic variant are more likely to have asthma exacerbations during a viral illness, and now we have greater understanding of how that happens.”

Rajesh Kumar, MD, Senior Author, Interim Division Head of Allergy and Clinical Immunology at Ann & Robert H. Lurie Children’s Hospital of Chicago and Professor of Pediatrics, Northwestern University Feinberg School of Medicine

“Our findings also may lead to future studies to help identify patients for whom treatment with mepolizumab may not be as effective and who may even have more of other types of inflammation that the drug does not block,” he said. “This is important to know in advance so the best therapeutic options could be considered earlier for these children. We are paving the way for precision medicine in pediatric asthma.”

For this study, Dr. Kumar and colleagues analyzed data and nasal samples from children with exacerbation-prone asthma, aged 6-17 years, that were included in previous studies.

Dr. Kumar cautioned that results show what is happening in the airway of patients with the SERPINE1 variant during a viral illness and in response to mepolizumab, as opposed to what would be seen clinically, since the study was not powered enough to reach a clinical conclusion. However, based on the function of these inflammatory pathways, he would expect that the presence of the genetic variant in a child with asthma, could translate to worse responses to mepolizumab in terms of asthma outcomes.

“Our study implies that during a viral illness, children with asthma who have the genetic variant may have more inflammation from the airway lining during viral illness compared to children without the variant, and this genetic difference creates distinct responses to mepolizumab,” said Dr. Kumar. “These insights bring us closer to being able to treat asthma according to each child’s individual genetic makeup. We are very excited about the enormous potential of precision medicine to improve asthma outcomes for children.”