Adding dupilumab to standard therapy for children 6 to 11 years of age with uncontrolled, moderate-to-severe asthma is associated with a significantly lower rate of severe asthma exacerbations, a clinically meaningful effect on lung function, and better asthma control. Dupilumab was also associated with rapid, sustained decreases in type 2 inflammation markers in airways and circulation, according to clinical trial findings published recently in the New England Journal of Medicine.

The multinational, randomized, placebo-controlled, Liberty Asthma VOYAGE phase 3 trial (ClinicalTrials.gov Identifier: NCT02948959), was designed to assess the efficacy and safety of dupilumab in children between 6 and 11 years of age with moderate-to-severe asthma. The trial included 405 children who received add-on dupilumab. For efficacy, patients were further observed as 2 populations: children with the type 2 inflammatory asthma phenotype (defined as a blood eosinophil count of ≥150 cells per cubic millimeter or a fractional exhaled nitric oxide [FeNO] of ≥20 ppb at baseline) and patients with a blood eosinophil count of at least 300 cells per cubic millimeter at baseline.

To study type 2 inflammatory asthma, researchers observed a cohort of 236 patients receiving add-on dupilumab (average age 8.9±1.6; 64.4% male) vs a placebo group of 114 patients (average age 9.0±1.6; 68.4% male). To study children with at least 300 eosinophils per cubic millimeter at baseline, researchers observed a cohort of 175 patients receiving add-on dupilumab (average age 8.9±1.6; 66.3% male) vs a placebo group of 84 patients (average age 9.0±1.5; 69.0% male). Patients with body weight exceeding 30 kg received 200 mg dupilumab or matching placebo, and patients with body weight of 30 kg or less received 100 mg dupilumab or matching placebo every 2 weeks for 1 year. All patients continued to receive a stable dose of standard background therapy.


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Patients with type 2 inflammatory phenotype presented an adjusted annualized rate of severe asthma exacerbations of 0.31 (95% CI, 0.22-0.42) in the dupilumab group and 0.75 (95% CI, 0.54-1.03) in the placebo group (relative risk reduction [RRR] in the dupilumab group, 59.3%; 95% CI, 39.5-72.6; P <.001). Patients with 300 or more eosinophils per cubic millimeter at baseline presented an adjusted annualized rate of severe asthma exacerbations of 0.24 (95% CI, 0.16-0.35) in the dupilumab group and 0.67 (95% CI, 0.47-0.95) in the placebo group (RRR, 64.7%; 95% CI, 43.8-77.8; P <.001). The percentage of patients with no exacerbations during the 52-week treatment was greater in the dupilumab group than the placebo group for both the type 2 phenotype and those with 300 or more eosinophils per cubic millimeter at baseline. Researchers noted patients in both dupilumab groups had lower risk of loss of asthma control than those in the 2 placebo groups.

Based on findings, researchers concluded, “Among the children between the ages of 6 and 11 years in our trial who had uncontrolled moderate-to-severe asthma, those who added dupilumab to their standard therapy had a significantly lower rate of severe asthma exacerbations and had better lung function and asthma control than those who received placebo.”

A limitation of this trial was a relative lack of ethnic diversity, particularly the low number of Black patients. Additionally, said researchers, “rapid decrease in the FeNO among the children receiving dupilumab could have given investigators a suspicion of trial-group assignment that could have had an effect on treatment decisions.”

Disclosure: This trial was funded by Sanofi and Regeneron Pharmaceuticals. Please see the original reference for a full list of disclosures. 

Reference

Bacharier LB, Maspero JF, Katelaris CH, et al. Dupilumab in children with uncontrolled moderate-to-severe asthma. N Engl J Med. Published online December 9, 2021. doi:10.1056/NEJMoa2106567