Dupilumab improved lung function, reduced exacerbations in children with type 2 asthma
Key takeaways:
- 74.3% of children had an allergic asthma phenotype.
- Dupilumab improved ppFEV1 scores that lasted through both trials.
BOSTON — Dupilumab reduced exacerbations and improved lung function in children with asthma, according to an abstract presented at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting.
“Over 80% of children with moderate to severe asthma that remains uncontrolled have evidence of elevated type 2 biomarkers,” Leonard B. Bacharier, MD, FACAAI, FAAAAI, Janie Robinson and John Moore Lee Chair in Pediatrics at Vanderbilt University Medical Center, said during his presentation. “In addition to that, a substantial proportion also have an allergic phenotype.”
Dupilumab (Dupixent; Regeneron, Sanofi) is a fully human monoclonal antibody that effectively blocks the shared receptor for both IL-4 and IL-13, which are key and central drivers of type 2 inflammation, Bacharier, who also is a member of the AAAAI/ACAAI Joint Task Force on Practice Parameters Severe and Difficult-to-Control Asthma Guideline Development Group, noted.
This post hoc analysis looked at data from the open-label extension EXCURSION study, which consisted of patients from the previous VOYAGE trial that were aged 6 to 11 years with uncontrolled, moderate to severe type 2 asthma (blood eosinophil counts 150 cells/µL or FeNO 20 ppb) using medium or high dose inhaled corticosteroids. It aimed to show that long-term dupilumab use (up to 104 weeks) had a strong safety profile, sustained exacerbation reduction and improved lung function.
The post-hoc analysis examined dupilumab efficacy of the patients in EXCURSION with or without evidence of allergic asthma. All children received dupilumab in the EXCURSION study, whereas in the VOYAGE trial, children received add-on dupilumab or placebo bi-weekly. Both studies lasted 52 weeks.
Out of 315 children, the analysis found that 74.3% had evidence of an allergic phenotype and 25.7% did not. Regardless of the presence of an allergic phenotype, dupilumab decreased annualized severe asthma exacerbations.
Children in the allergic phenotype dupilumab group (n = 159) in the VOYAGE trial had an unadjusted annualized severe exacerbation rate of 0.333 compared with 0.651 among children in the placebo group (n = 75) at 52 weeks. In the EXCURSION study, the dupilumab group (n = 160) had a rate of 0.117, and the placebo to dupilumab group (n = 74) had a rate of 0.083 at the same time point.
“Since no child can actually have a tenth of an exacerbation, this really equates to one child out of 10 having an exacerbation or almost nine out of 10 not having an exacerbation,” Bacharier said.
Children without an allergic phenotype in the dupilumab group (n = 49) in the VOYAGE trial had a rate of 0.429 compared with 0.749 in children in the placebo group (n = 32) at 52 weeks, and in the EXCURSION study, the dupilumab non-allergic phenotype group (n = 49) had a rate of 0.122 compared with the placebo to dupilumab group (n = 32) rate of 0.218.
In the VOYAGE trial, dupilumab significantly improved pre-bronchodilator percent-predicted FEV1 among allergic phenotype children with effects lasting through the EXCURSION study. The same was seen in children with a non-allergic phenotype.
“Those who received dupilumab throughout had an early improvement during VOYAGE that was sustained in terms of percent-predicted FEV1 and that was maintained throughout EXCURSION,” Bacharier said.
“Those who received placebo during VOYAGE had a modest improvement, but at the initiation of EXCURSION when dupilumab was started, there was a rapid and sustained improvement in their lung function,” he continued. “But as you can see, they never quite catch the children who started dupilumab in year one.”
Bacharier also noted that about 40% of the time in EXCURSION was spent during the early part of the COVID-19 pandemic. This contributed to the COVID effect of exacerbation near elimination. However, on secondary analysis, the study team did not feel that this drove the marked reduction in exacerbations.