Type 2 asthma paediatric patients eligible for dupilumab: An Italian biomarker-based analysis

Background: Type 2 inflammation is the principal determinant of asthma in children, and it leads to the downstream activation of eosinophils (EOS), the production of immunoglobulin-E (IgE), and increased levels of fraction of exhaled nitric oxide (FeNO). Dupilumab received the approval for the treatment of uncontrolled severe Type 2 asthma in children. Objective: The aim of this analysis was to calculate the Type 2 severe asthma paediatric population who would be eligible for treatment with dupilumab in Italy and characterize them by expected biomarker status. Methods: The calculation of the dupilumab-eligible population employed a two-phase approach: 1) estimating the total number of children aged 6–11 years with uncontrolled severe asthma; and 2) stratifying the severe uncontrolled asthma population, based on appropriate biomarker levels, thus identifying patients eligible for treatment with dupilumab. The VOYAGE study provided the data for this analysis. Results: The two-phase approach utilizing VOYAGE data revealed that the average number of paediatric patients with uncontrolled severe asthma was N = 1007. Stratification of these patients, as per VOYAGE data, indicated that the majority (N = 740; 73.5%) would have ≥2 elevated biomarkers, and over one-third patients (N = 434, 43.1%) would exhibit simultaneously elevated levels of EOS, FeNO and IgE. Of the paediatric patients, N = 864 were identified as eligible to dupilumab treatment, constituting 85.8% of the target population. Notably, nearly half eligible patients (N = 454) displayed elevated levels of both EOS and FeNO biomarkers, while the substantial majority (81.1%) exhibited at least an increase of EOS levels (N = 817). Patients with increased FeNO levels without a concurrent increase in EOS were less frequent (N = 47; 5.4% of the eligible population). Conclusion: The simultaneous testing of multiple biomarkers during baseline patient assessment and disease follow-up is highly recommended. Utilizing cost-effective tests, physicians can estimate the prevalence of severe Type 2 asthma, categorize patients into distinct phenotypes (eosinophilic, allergic, or mixed), and consequently identify and prescribe the most suitable therapeutic interventions. This approach also facilitates the ongoing evaluation and adjustment of the treatment strategies based on individual patient responses.