Prognostic utility of pre-biologic treatment correlates of childhood severe asthma exacerbation risk: Real world evidence.

BACKGROUND: Biologics have been shown to substantially reduce the risk of severe asthma exacerbations (SAEs) among children with moderate or severe asthma; however, not all eligible patients who initiate biologic treatment experience a reduced risk of SAEs. METHODS: Using a longitudinal study design, we analyzed data from 122 children with moderate/severe asthma treated with a biologic by pediatric subspecialists between December 2019 and December 2024. We used logistic and Cox proportional hazards models to identify and quantify the prognostic utility of clinical correlates of increased SAE risk among children with moderate or severe asthma prior to biologic treatment initiation. RESULTS: Biologic agents (dupilumab, omalizumab, and mepolizumab) had differential effects on the risk of SAE depending on a child's sex (p = .024), age of treatment initiation (p = .010), lung function (% FEF25-75 predicted: p = .034), and absolute neutrophils (p = .055). Dupilumab was associated with a higher risk of SAE among female patients. Omalizumab and mepolizumab were associated with a higher risk of SAEs among patients with elevated absolute neutrophils and younger age at treatment initiation. Consideration of these clinical parameters in a multivariable model improved the pre-treatment prognostic accuracy of SAE risk by 23% compared to reliance on history of SAEs alone (0.86; 95% CI: 0.79, 0.89 vs. 0.63; 95% CI: 0.54, 0.72). CONCLUSION: Beyond biologic treatment eligibility, using routinely collected clinical parameters to stratify pre-treatment SAE risk could improve prognostic accuracy and aid clinicians in tailoring therapy based on a patient's individual risk factors and likelihood of responding to a specific agent to maximize treatment effectiveness.