Study Highlight

Bacharier LB, Maspero JF, Papadopoulos NG, et al. Dupilumab Plus MediumDose Inhaled Corticosteroid ICS Improves Outcomes Compared With Placebo Plus Continued HighDose ICS in Children With Uncontrolled ModeratetoSevere Type 2 Asthma. Pediatr Pulmonol. 2025;60(7):e71197. doi:10.1002/ppul.71197.

Introduction

Moderate-to-severe asthma in children, especially with a type 2 inflammatory phenotype, remains a significant clinical challenge, often requiring high-dose inhaled corticosteroids (ICS) to achieve disease control. However, long-term use of high-dose ICS raises concerns about side effects and the need for newer therapeutic strategies that can improve asthma control and reduce exacerbations while minimizing steroid exposure.

Dupilumab, a monoclonal antibody targeting IL-4 and IL-13 pathways, has shown promise in reducing type 2 inflammation and improving asthma outcomes. Evaluating the efficacy of dupilumab combined with medium-dose ICS versus continued high-dose ICS alone in children offers important insights into optimizing treatment regimens in this vulnerable population.

Study Overview

Study Type: Phase 3 randomized controlled trial (VOYAGE study, NCT02948959) assessing efficacy and safety over 52 weeks

Population: 184 children aged 6-11 years with uncontrolled moderate-to-severe asthma characterized by type 2 inflammation (blood eosinophils ≥150 cells/μL or FeNO ≥20 ppb)

Intervention: Dupilumab dosed at 100 mg or 200 mg every 2 weeks (weight-adjusted) plus medium-dose ICS, versus placebo every 2 weeks plus continued high-dose ICS

Outcomes: Annualized severe asthma exacerbation rates, changes in lung function (pre-bronchodilator ppFEV1, morning peak expiratory flow), asthma control questionnaire scores (ACQ-7-IA), biomarkers (FeNO, blood eosinophils, total IgE)

Key Findings

Evidence Synthesis

The findings from this study extend the established benefits of dupilumab in pediatric asthma treatment, aligning closely with evidence from the parent LIBERTY ASTHMA VOYAGE trial and subsequent analyses that highlight the drug’s efficacy in reducing exacerbations and improving lung function in children with type 2 inflammation.

Table 1 summarizes key related studies that contextualize and reinforce these results:

This integrated evidence concisely supports the role of dupilumab combined with medium-dose ICS as a safe and efficacious strategy to reduce steroid exposure while optimizing asthma outcomes in children with type 2 inflammation.

Clinical Implications

These robust findings have several important clinical takeaways for practitioners managing pediatric asthma:

• Consider dupilumab addition when seeking to reduce ICS dose while maintaining or improving asthma control in children with type 2 inflammation.
• Biomarker profiling using blood eosinophils and FeNO can aid in identifying patients most likely to benefit from dupilumab therapy.
• Improvements in lung function and symptom control support dupilumab’s integration as a disease-modifying therapy, potentially enhancing quality of life for patients and caregivers.
• Ongoing monitoring and tailored adjustment remain critical due to variability in patient response and to achieve optimal long-term management.

Strengths & Limitations

Future Directions

Future research should focus on prospective studies to refine risk stratification models incorporating biomarkers, long-term safety and efficacy assessments beyond 1 year, and head-to-head trials comparing dupilumab with other biologic agents in pediatric asthma. Additionally, investigations into personalized step-down ICS strategies combined with biologics could optimize treatment protocols and improve patient-centered outcomes.

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References

1. Bacharier LB, Maspero JF, Katelaris CH, et al. Dupilumab in Children with Uncontrolled Moderate-to-Severe Asthma. N Engl J Med. 2021 Dec 9;385(24):2230-2240. doi:10.1056/NEJMoa2106567. PMID: 34879449.
2. Bacharier LB, Guilbert TW, Katelaris CH, et al. Dupilumab Improves Lung Function Parameters in Pediatric Type 2 Asthma: VOYAGE Study. J Allergy Clin Immunol Pract. 2024 Apr;12(4):948-959. doi:10.1016/j.jaip.2023.12.006. PMID: 38092225.
3. Bacharier LB, Pavord ID, Maspero JF, et al. Blood eosinophils and fractional exhaled nitric oxide are prognostic and predictive biomarkers in childhood asthma. J Allergy Clin Immunol. 2024 Jul;154(1):101-110. doi:10.1016/j.jaci.2023.09.044. PMID: 38272375.
4. Blaiss MS, Chipps BE, Phipatanakul W, et al. Dupilumab Efficacy in Children With Type 2 Asthma Receiving High- or Medium-Dose ICS. J Allergy Clin Immunol Pract. 2024 Nov;12(11):2841-2845.e3. doi:10.1016/j.jaip.2024.08.016. PMID: 39209068.
5. Chipps BE, Phipatanakul W, Deschildre A, et al. Impact of Exacerbation History on Dupilumab Efficacy in Children With Asthma. J Allergy Clin Immunol Pract. 2024 May;12(5):1257-1265.e4. doi:10.1016/j.jaip.2024.02.023. PMID: 38476213.
6. Deschildre A, Phipatanakul W, Blaiss MS, et al. Dupilumab Efficacy and Safety in Children With Moderate to Severe Asthma and High Eosinophils. J Allergy Clin Immunol Pract. 2024 Dec;12(12):3134-3138.e3. doi:10.1016/j.jaip.2024.09.034. PMID: 39613097.
7. Phipatanakul W, Chipps BE, Scheerens H, et al. Dupilumab leads to better-controlled asthma and quality of life in children and caregivers. J Allergy Clin Immunol Pract. 2023 Nov;11(11):3423-3432.e4. doi:10.1016/j.jaip.2023.09.020. PMID: 37734856.