Dupilumab Clinical Trial Data Suggest Safety, Efficacy for Allergic Asthma in Children

Results from a recent systematic review of children and adolescents with moderate to severe allergic asthma suggest dupilumab use likely reduces the annual severe exacerbation rate, improves symptom control, and increases the percentage of children with good quality of life (QOL) and pulmonary function parameters, all without serious adverse events.¹

The Th2 phenotype of asthma is notoriously difficult to treat; several immunological markers of this phenotype are associated with poor symptom control, repeated exacerbations, and greater allergic sensitization and air-flow obstruction. To address these pathways, several monoclonal antibodies have been developed, such as dupilumab, which specifically targets the IL-4 and IL-13 receptor alpha subunit.^1,2

Despite the efficacy of dupilumab in treating this specific phenotype, clinical trials investigating the drug do not properly represent children and adolescents. This prevents the application of these findings to the younger population.¹

“Early systematic reviews assessing the efficacy of Dupilumab in asthma did not include school-aged children, which restricts the generalizability of their conclusions,” wrote Roxana Aznaran-Torres, MD, Antenor Orrego Private University, and colleagues. “Consequently, our objective was to evaluate the benefits and harms of Dupilumab in children and adolescents with moderate to severe asthma through a systematic review and meta-analysis of randomized clinical trials (RCTs).”¹

Investigators collected RCTs from various databases including PubMed, Embase, and Cochrane Library. An initial total of 379 articles were identified; after removing duplicates, 227 titles and abstracts were screened, and 92 full texts were reviewed. A final count of 7 publications from 2 RCTs was included.¹

Both RCTs were multicenter trials conducted in multiple countries; the first, VOYAGE, enrolled 408 children aged 8.9 +/- 1.7 years with moderate-to-severe asthma uncontrolled by standard therapy. The Simpson study included 251 patients (53.6% with asthma) aged ≥12 to <18 years with severe atopic dermatitis. Participants of both trials continued standard asthma therapies. Although investigators intended a meta-analysis for each outcome, it was restricted to outcomes with >1 study. As a result, it was only performed for the asthma control outcome.¹

In the VOYAGE trial, dupilumab was administered subcutaneously every 2 weeks (100 mg for weight ≤30 kg, 200 mg for >30 kg) for 52 weeks. The Simpson study used 200/300 mg every 2 weeks or 300 mg every 4 weeks based on body weight for 16 weeks.¹

The team noted the success of dupilumab in reducing severe asthma exacerbations compared to placebo in the VOYAGE trial (incidence rate ratio [IRR], .46; 95% CI, .31 to .67; moderate certainty). Subgroups with type 2 inflammation (IRR, .35; 95% CI, .2 to .6) or eosinophils ≥150 cells/µl and FeNO <20 ppb (IRR, .47; 95% CI, .26 to .85) exhibited similar reductions (moderate certainty). These benefits extended to patients with (RR, .38; 95% CI, .24 to .61) and without (crude relative risk [RR], .49; 95% CI, .24 to 1) allergic asthma.¹

Dupilumab also reduced Asthma Control Questionnaire scores compared to placebo (mean difference [MD], -.43; 95% CI, -.56 to -.3; moderate certainty). Type 2 inflammation was also lowered (least squares mean difference [LS-MD], -.33; 95% CI, -.5 to -.16). Improved asthma control was displayed in type 2 inflammation (RR, 1.18; 95% CI, 1.07 to 1.26). Dupilumab also reduced the risk of asthma control loss (HR, .69; 95% CI, .52 to .9).¹

Investigators also noted the 83% incidence rate of adverse events in the dupilumab subgroup compared to 79.9% in the placebo group during the VOYAGE trial. Viral upper respiratory infections were the most common (12.2% versus 9.7%); serious adverse events included eosinophilia (RR, 1.05; 95% CI, .41 to 2.68; low certainty), which led to one treatment discontinuation.¹

“From a clinical standpoint, the integration of dupilumab into asthma management requires a precision medicine approach, incorporating patient phenotyping and biomarker-driven selection to maximize therapeutic benefits,” wrote Aznaran-Torres and colleagues. “Clinicians should remain vigilant regarding eosinophilia-related complications and ocular symptoms, ensuring appropriate monitoring protocols are in place.”¹

References

1. Aznaran-Torres R, Nombera-Lossio J, Arredondo-Nontol M, et al. Effects of Dupilumab in Children and Adolescents With Moderate-Severe Asthma: A Systematic Review of Clinical Trials. Pediatr Pulmonol. 2025;60(5):e71138. doi:10.1002/ppul.71138

2. Fitzpatrick AM, Gaston BM, Erzurum SC, Teague WG; National Institutes of Health/National Heart, Lung, and Blood Institute Severe Asthma Research Program. Features of severe asthma in school-age children: Atopy and increased exhaled nitric oxide. J Allergy Clin Immunol. 2006;118(6):1218-1225. doi:10.1016/j.jaci.2006.08.019