Dupilumab in Children with Uncontrolled Moderate-to-Severe Asthma.

Abstract

BACKGROUND:

Children with moderate-to-severe asthma continue to have disease complications despite the receipt of standard-of-care therapy. The monoclonal antibody dupilumab has been approved for the treatment of adults and adolescents with asthma as well as with other type 2 inflammatory diseases.

METHODS:

In this 52-week phase 3, randomized, double-blind, placebo-controlled trial, we assigned 408 children between the ages of 6 and 11 years who had uncontrolled moderate-to-severe asthma to receive a subcutaneous injection of dupilumab (at a dose of 100 mg for those weighing ≤30 kg and 200 mg for those weighing >30 kg) or matched placebo every 2 weeks. All the children continued to receive a stable dose of standard background therapy. The primary end point was the annualized rate of severe asthma exacerbations. Secondary end points included the change from baseline in the percentage of predicted prebronchodilator forced expiratory volume in 1 second (ppFEV1) at week 12 and in the score on the Asthma Control Questionnaire 7 Interviewer-Administered (ACQ-7-IA) at week 24. End points were evaluated in the two primary efficacy populations who had either a type 2 inflammatory asthma phenotype (≥150 blood eosinophils per cubic millimeter or a fraction of exhaled nitric oxide of ≥20 ppb at baseline) or a blood eosinophil count of at least 300 cells per cubic millimeter at baseline.

RESULTS:

In patients with the type 2 inflammatory phenotype, the annualized rate of severe asthma exacerbations was 0.31 (95% confidence interval [CI], 0.22 to 0.42) with dupilumab and 0.75 (95% CI, 0.54 to 1.03) with placebo (relative risk reduction in the dupilumab group, 59.3%; 95% CI, 39.5 to 72.6; P<0.001). 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). Similar results were observed in the 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 two groups.

CONCLUSIONS:

Among children with uncontrolled moderate-to-severe asthma, those who received add-on dupilumab had fewer asthma exacerbations and better lung function and asthma control than those who received placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; Liberty Asthma VOYAGE ClinicalTrials.gov number, NCT02948959.).

• Authors: Leonard B Bacharier, Jorge F Maspero, Constance H Katelaris, Alessandro G Fiocchi, Remi Gagnon, Ines de Mir, Neal Jain, Lawrence D Sher, Xuezhou Mao, Dongfang Liu, Yi Zhang, Asif H Khan, Upender Kapoor, Faisal A Khokhar, Paul J Rowe, Yamo Deniz, Marcella Ruddy, Elizabeth Laws, Naimish Patel, David M Weinreich, George D Yancopoulos, Nikhil Amin, Leda P Mannent, David J Lederer, Megan Hardin, Liberty Asthma VOYAGE Investigators
• Journal: The New England journal of medicine (N Engl J Med) Vol. 385 Issue 24 Pg. 2230-2240 (12 09 2021) ISSN: 1533-4406 [Electronic] United States
• PMID: 34879449 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Massachusetts Medical Society.

Chemical References

• Anti-Asthmatic Agents
• Antibodies, Monoclonal, Humanized
• Biomarkers
• Nitric Oxide
• dupilumab

Topics

• Anti-Asthmatic Agents (administration & dosage, adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects, therapeutic use)
• Asthma (drug therapy, physiopathology)
• Biomarkers (analysis)
• Breath Tests
• Child
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Forced Expiratory Volume
• Humans
• Injections, Subcutaneous
• Lung (physiopathology)
• Male
• Nitric Oxide (administration & dosage)
• Patient Acuity
• Symptom Flare Up