Dupilumab Efficacious in Children with Moderate-to-Severe Asthma

Leonard Bacharier, MD

New data on the monoclonal antibody dupilumab found that children with moderate-to-severe asthma had fewer asthma exacerbations and improved lung function when treated with the biologic than those who received placebo.

The findings came from the Liberty Asthma VOYAGE trial, which was funded by Sanofi and Regeneron Pharmaceuticals.

Dupilumab has been approved for the treatment of adults and adolescents with asthma in addition to other type 2 inflammatory diseases.

For the present study, Leonard Bacharier, MD, Division of Allergy, Immunology, and Pulmonary Medicine, Monroe Carell Jr. Children’s Hospital at Vanderbilt University Medical Center, and fellow investigators assessed the efficacy and safety of the biologic in children between the ages of 6 and 11 years with moderate-to-severe asthma.

The Methods

Any child was eligible for participation in the study if they had physician-diagnosed moderate-to-severe asthma according to Global Strategy for Asthma Management and Prevention (GINA) guidelines.

As such, investigators recruited a total of 408 patients.

Each patient completed a screening period of 4 weeks, followed by randomization into 1 of 2 groups. A total of 273 patients were randomized into the dupilumab group, while 135 patients were placed in the placebo group.

During the screening period, patients were required to have at least a 3-month history of receiving either a medium-dose inhaled glucocorticoid with a second controller or a high-dose of inhaled glucocorticoid alone or in combination with a second controller at a dose that had been stable for at least 1 month before screening.

Patients in the dupilumab group who weighed ≤30 kg received a dose of 100 mg of the biologic, while children weighing >30 kg received 200 mg. Those in the placebo group received matched doses, and all patients received treatment every 2 weeks for 52 weeks.

Asthma control was assessed with the Asthma Control Questionnaire 7 Interviewer-Administered (ACQ-7-IA) questionnaire.

The primary endpoint of the study was the annualized rate of severe asthma exacerbations, while the secondary end points included the change from baseline in the percentage of predicted prebronchodilator forced expiratory volume in 1 second at week 12 and in the score of the ACQ-7-IA at week 24.

The Findings

Investigators found that the annualized rate of severe asthma exacerbations was 0.31 (95% confidence interval [CI], 0.22 to 0.42) with those in the dupilumab group and 0.75 (95% CI, 0.54 to 1.03) with the placebo group.

Additionally, the mean (±SE) change from baseline in the ppFEV1 was 10.5±1.0 percentage points with dupilumab and 5.3±1.4 percentage points with placebo (mean difference, 5.2 percentage points; 95% CI, 2.1 to 8.3; P<0.001).

Dupilumab also resulted in significantly better asthma control than placebo (P<0.001). Treatment with the biologic led to significant improvements in all end points in the testing hierarchy, and significant reductions in severe exacerbations and improvement in lung function were deemed clinically relevant,

Investigators recorded similar results regarding patients with an eosinophil count of at least 300 cells per cubic millimeter at baseline. The incidence of serious adverse events was similar in the dupilumab and placebo groups.

The team added that dupilumab “Also had an acceptable side-effect profile in patients between the ages of 6 and 11 years with uncontrolled moderate-to-severe asthma and a type 2 inflammatory asthma phenotype.”

The study, “Dupilumab in Children with Uncontrolled Moderate-to-Severe Asthma,” was published online in the New England Journal of Medicine.