Effectiveness and safety of dupilumab in children with moderate-to-severe asthma in China: A retrospective real-world study

To the editor: Type 2 inflammation is a major driving factor in pediatric moderate-to-severe asthma, which may lead to the activation of downstream eosinophils, immunoglobulin E (IgE) production, increased fractional exhaled nitric oxide (FeNO), and airway mucus production.[1] Despite adequate treatment with medium-high dose inhaled corticosteroids combined with long-acting β2-receptor agonists (ICS–LABAs) for pediatric moderate-to-severe asthma, symptoms persist or frequently worsen.[2] Studies have shown that approximately 70–89% of children with moderate-to-severe asthma have type 2 inflammation, and a major endotype is type 2 asthma, characterized by the presence of elevated type 2 biomarkers, including blood or sputum eosinophils, total IgE with allergic sensitization, and FeNO.[3] Dupilumab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody to the alpha subunit of the interleukin-4 receptor (IL-4R). By binding with the IL-4R, it can simultaneously inhibit the binding of interleukin-4 (IL-4) and interleukin-13 (IL-13) to the IL-4R, block downstream signal transduction, reduce eosinophilic recruitment, and thus reduce airway eosinophilic inflammation.[4] It has been reported to show good efficacy in patients with moderate-to-severe asthma that remains uncontrolled even after high-dose inhaled corticosteroids or other treatments. Dupilumab has been approved for the long-term maintenance treatment in adolescents aged 12 and above and adult patients with asthma in China. Because there is currently no comprehensive data to support the efficacy or safety of dupilumab in the treatment of pediatric moderate-to-severe asthma in China, we initiated a retrospective study aiming to investigate the effectiveness and safety of dupilumab in this specific population through real-world data. The Institutional Ethical Review Board of the First Affiliated Hospital of Guangzhou Medical University approved the study (No. ES-2024-001-01). The requirement to obtain informed consent from the patients was waived. The historical clinical data of children with moderate-to-severe asthma who were prescribed with dupilumab between January 1, 2022 and December 31, 2023 were obtained. Patient inclusion criteria were: (1) Children aged 6–14 years met the diagnostic criteria for moderate-to-severe asthma according to the Global Initiative for Asthma (GINA) 2022 guidelines for pediatric asthma. (2) Children with asthma who were not well controlled on median to high dose of inhaled glucocorticoids (ICS) combined with long-acting β2-receptor agonists (LABA) or leukotriene receptor antagonists (LTRA). (3) All asthma children were accompanied by characteristics of type 2 inflammation and prescribed with dupilumab. The type 2 inflammatory asthma was defined as either FeNO ≥20 parts per billion (ppb) or sputum eosinophils percentage (%) ≥2% or blood eosinophils count ≥300 cells/μL. Exclusion criteria were patients: (1) Using dupilumab to treat diseases other than asthma. (2) Currently using other biological agents or undergoing sublingual and subcutaneous desensitization therapies. Patients who met the inclusion criteria were included in the whole cohort. Compared to adolescents (age ≥12 years old), there is currently a lack of efficacy and safety data for patients with moderate-to-severe asthma in the childhood group (age <12 years old). Also, in order to ensure a focused analysis on the pediatric subgroup recommended for dupilumab treatment under the GINA guidelines, in this study, patients aged 6–11 years were selected as the subgroup. The primary endpoints were the change from baseline at different follow-up timepoints (0 month