Clinical trials use precision medicine to test treatments for severe asthma

Asthma severity can be affected by multiple inflammatory pathways, which make it challenging to treat with a “one size fits all” approach. This is why researchers started pursuing precision medicine for asthma – distinguishing disease types based on specific biological signs (called biomarkers) and matching treatments to the patient’s asthma type.

“With a trial that uses precision medicine as a way to direct subjects to the potentially most optimal treatment for their type of profile, we are attempting to apply to asthma an approach that proved successful with cancer studies. This is called a platform trial where multiple interventions are examined in subjects who participate in the trial. This is particularly important since asthma that is severe and associated with risk of exacerbations is variable in the types of inflammation present and needs additional precise options for treatment,” said Rajesh Kumar, MD, Interim Division Head of Allergy and Immunology at Ann & Robert H. Lurie Children’s Hospital of Chicago and Professor of Pediatrics at Northwestern University Feinberg School of Medicine. “This is an exciting first for asthma research.”

Dr. Kumar is the Lurie Children’s site Principal Investigator for the Precision Interventions for Severe and/or Exacerbation-Prone Asthma (PrecISE) Network, a groundbreaking collaborative of asthma researchers from across the United States. He also is on the Steering Committee, the Publications Committee and the New Approaches Committee of the PrecISE Network.

“In the PrecISE study we looked at six different treatments overall, but in adolescents we limited these to only two treatments with the best safety profile in children – a nutritional supplement called MCT (medium-chain triglycerides) or an immune modulating mixture of bacterial breakdown products (called broncho-vaxom). In the subjects who were included at Lurie Children’s, we evaluated two immunomodulatory treatments against a placebo. The treatment that was chosen first was based on biomarkers relevant to asthma,” said Dr. Kumar. “Subjects had the option to continue to the next treatment period sequentially to test the second drug, in order to see if the biomarker predicted treatment response.”

A number of biomarkers were included, but key biomarkers that were expected to increase the chances of response were used to increase the likelihood that a participant would be scheduled and randomized to test each treatment.

Nitric oxide, which is a gas produced as part of the allergic inflammation in the airways, was the biomarker that increased the likelihood that an adolescent would be placed on MCT.

Adolescents with high levels of eosinophils –a type of white blood cells that are involved in the immune response and contribute to inflammation in allergic asthma –were more likely to be first included in the arm of the study testing bronco-vaxom.

The study completed the clinical phase and is now undergoing data analysis.

“We hope that this study will promote further precision medicine studies that transform asthma care,” said Dr. Kumar. “Ultimately, we hope to be able to characterize a patient’s asthma based on biomarkers and select a treatment that is most effective for that asthma type across multiple types of asthma, not just allergic asthma.”

PrecISE Network is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health.