Factors Influencing the Initiation of Biologic Therapy in Children With Severe Asthma: Results of the Pediatric Asthma Noninvasive Diagnostic Approaches (PANDA) Study

This observational study aimed to identify and compare the real- world factors with the Global Initiative for Asthma (GINA) guidelines in driving or inhibiting the initiation of biologic therapy in children with severe asthma.This prospective cohort included 72 Dutch children aged 6 to 17 years (mean 11.5 ± 3.0 years, 65.3% male) with severe asthma (GINA step 3 or higher) who were referred for one of the biologic therapies covered by the European Medicines Agency (EMA) as part of routine asthma care between May 2020 and December 2023. The pediatric pulmonologist clinically determined the “starters” (n = 13), who initiated biologic therapy, and the “nonstarters” (n = 59), who did not.Asthma control test (ACT) scores, modifiable risk factors (exacerbations, tobacco exposure, pet exposure), comorbidities (allergic rhinitis, eczema, food allergy, obesity, steroid toxicity), medication adherence report scale (MAR-5), and spirometry data were collected through medical record review and standardized questionnaires. Multivariable logistic regression was used to determine independent predictors of biologic therapy initiation. Suitability for biologic treatment according to GINA criteria (type 2 inflammatory biomarkers, exacerbation frequency, and medication adherence) was also assessed.The initiation of omalizumab (n = 12) or mepolizumab (n = 1) was significantly associated with a higher GINA treatment step (mean step 5.2 vs 4.6; P = .03), presence of steroid-related toxicity (54% of starters vs 10% of nonstarters; adjusted odds ratio [aOR] 21.1; 95% CI, 3.73–119.91), increased exacerbation frequency (mean 2.6 vs 1.5 exacerbations/y; aOR 1.6; 95% CI, 1.10–2.39), and good adherence to asthma medication (aOR 1.7; 95% CI, 1.10–2.46). Factors associated with the decision not to initiate biologic therapy included being white (aOR 0.20; 95% CI, 0.05–0.85), having at least 1 allergic sensitization (aOR 0.06; 95% CI, 0.01–0.51), and having allergic rhinitis (aOR 0.13; 95% CI, 0.02–0.75). Of the 13 starters, 5 would not have met GINA guidelines for initiating biologics; however, 4 of these patients were started due to steroid toxicity and 1 due to adherence issues. The 16 other patients who were indicated for biologics per GINA received either an alternative intervention or step-up medical treatment or deferred biologic treatment. Dupilumab became an option for 5 starters but was not prescribed.The decision to start biologic therapy in children with severe asthma was influenced by clinical severity, steroid-related side effects, and adherence, rather than strict adherence to guideline criteria. Allergic comorbidities and health disparities associated with ethnicities possibly played a role in decisions to withhold therapy. These findings suggest that real-world clinical judgment sometimes does not align with guideline-based eligibility.This study provides important insights into the real-world application of biologic therapy in pediatric asthma but was only performed in 1 country, with a small number of patients and apparently limited biologic availability. Its prospective design and careful phenotyping of a severe asthma cohort are strengths. A key clinical takeaway is that pediatric clinicians often prioritize mitigating steroid toxicity over meeting all GINA-defined criteria when initiating biologic treatment. This observation demonstrates a potential gap between guideline-based eligibility and practical decision-making. Practice and health care system biases by country and region limit the generalizability and statistical power of this study. Future research should include a larger cohort treated by pediatric allergists, potentially with access to all available biologics, to validate these findings and examine how comorbidities and sociodemographic factors influence treatment decisions across diverse populations.