Approximately 5% of children with asthma develop severe diseases, which are associated with significantly higher morbidity and more than threefold greater healthcare costs compared to those with milder asthma. This highlights the importance of early identification as well as timely intervention. The U.S. Food and Drug Administration (FDA) has approved four biologic therapies, such as benralizumab, dupilumab, omalizumab, and mepolizumab, especially for children aged ≥6 years. These monoclonal antibodies can decrease severe asthma exacerbations, such as emergency visits and hospitalizations, by 27 to 54%. However, uncertainties remain regarding their long-term and comparative effectiveness, as well as whether early treatment initiation can change the progression of the disease. A recent study published in Annals of the American Thoracic Society aimed to evaluate the benefits of biologic therapy by examining early childhood asthma risk factors, age at treatment initiation, and biologic type, and how these factors influence the treatment response.
In this retrospective cohort study, electronic health record (EHR) data of children were collected from the Indiana Network for Patient Care (INPC) and the Indiana University Health (IUH). A total of 122 children (female = 50.8%, male = 49.2%, Black/African American = 60.7%, Non-Hispanic = 95.9%) receiving biologic therapy from 2019 to 2024 were included. Patients with prior biologic use or biologics prescribed for other health conditions were excluded from the study. The first biologic prescription served as the index date, which defines the post-treatment period (1-3 years after) and pre-treatment period (1-6 years before). The primary endpoint was severe asthma exacerbation leading to emergency department visits or hospitalization. Early childhood risk factors such as wheezing, allergic sensitization, eczema, parental asthma, and infections were detected by using EHR data. Statistical analyses included Kaplan-Meier curves, piecewise generalized linear mixed effects models, Andersen-Gill models, and sensitivity analysis.
Cohort participants had a mean age of 3.1±3.6 years at initial asthma diagnosis and 10.5±3.7 years at the start of biologic therapy. Among the 122 patients, 63.1% received dupilumab, 9.8% mepolizumab, 27% omalizumab, whereas benralizumab was not prescribed during the 10-years of follow-up study period. Approximately 54% initiated biologic therapy at ages 6-11 years and 46% at ≥12 years. Patients diagnosed with asthma at 12 years or older were initiated on biologic therapy sooner compared to those diagnosed earlier, with p <0.001. Older age at diagnosis of asthma was associated with a 46% higher likelihood of earlier biologic initiation with a hazard ratio (HR) of 1.46 (95% confidence interval [CI]: 1.33-1.60). Cluster analysis identified three allergy sensitization clusters explaining 57.6% variability. Cluster 2 demonstrated higher sensitization to fungi, pet dander, seasonal allergens, and dust mites, whereas cluster 3 had more food allergies such as milk, nuts, and seafood.
Before biologic initiation, the annual incidence of severe asthma exacerbations increased from 16% to 46% but declined markedly after treatment to 15% in the first year and 16 to 19% in subsequent years. Overall, biologic therapy reduced exacerbations by approximately 53% with an adjusted odds ratio (OR) of 0.47 (95% CI: 0.28-0.80). Earlier initiation was linked to better outcomes with adjusted OR of 0.46 (95% CI: 0.26-0.80) for ages 6-11 years vs. 0.56 (95% CI: 0.27-1.89) for ≥12 years. Sensitivity analyses revealed that higher recurrence rates of exacerbations with mepolizumab (adjusted HR = 2.55 [95% CI: 1.50-4.34]) and omalizumab (adjusted HR = 2.73 [95% CI: 1.78-4.17]) compared to dupilumab. Patients with moderate to high early childhood risk showed greater benefit from biologics. Additionally, females had a higher prevalence of treatment risk compared to males.
This study has several limitations, including its real-world design, possible EHR data errors, small sample size, non-randomized biologic selection, potential allergy misclassification, varying approval timelines of biologics, and residual confounding.
In conclusion, early biologic therapy in children with severe asthma reduces the risk of severe exacerbations. Treatment benefits may vary depending on age at initiation and early-childhood risk profiles, which suggest that risk-based screening could help identify children most likely to benefit from biologic therapy.
Reference: Owora AH, Kloepfer K, Tepper R, et al. Real-world effectiveness of asthma biologics by age of initiation and early-childhood risk factors. Ann Am Thorac Soc. 2026. doi:10.1093/annalsats/aaoag019
