Emerging Paediatric Uses of Dupilumab Beyond Approvals

Abstract

Dupilumab is a fully human IgG4 monoclonal antibody that targets the interleukin-4 receptor alpha subunit, thereby inhibiting interleukin-4 and interleukin-13 signalling, two central drivers of type-2 (T2) inflammation. It is currently approved by both the Food and Drug Administration and the European Medicines Agency for multiple indications, including moderate-to-severe atopic dermatitis (from 6 months of age), add-on maintenance therapy for moderate-to-severe asthma with T2 inflammation (≥ 6 years), eosinophilic esophagitis (≥ 1 year and ≥ 15 kg), chronic rhinosinusitis with nasal polyps (≥ 12 years in the United States and ≥ 18 years in Europe), and chronic spontaneous urticaria (≥ 12 years in the United States and ≥ 2 years in Europe) who remains symptomatic despite antihistamine therapy. Additional adult indications include prurigo nodularis, bullous pemphigoid, and chronic obstructive pulmonary disease with an eosinophilic phenotype. Beyond these established indications, increasing evidence suggests a broader therapeutic potential for dupilumab in paediatric diseases characterized by T2 immune dysregulation. This narrative review synthesizes the emerging literature on off-label and investigational paediatric uses of dupilumab, focusing on inflammatory skin diseases, inborn errors of immunity with severe atopic phenotypes, transplant-associated immune dysregulation, selected respiratory conditions and food allergy. Although current evidence largely derives from case reports, small case series, and observational studies, reported outcomes consistently indicate significant improvements in disease severity, and quality of life, with a favourable safety profile. These findings highlight the expanding role of IL-4/IL-13 blockade in paediatrics and underscore the need for prospective studies to better define efficacy, long-term safety, and optimal patient selection in emerging indications.