Understanding Heterogeneous Responses to Asthma Biologics in Children

A real-world cohort study analyzed data from 122 children treated with biologics, highlighting candidate predictors and clinical outcomes.

The investigators assessed sex, age at treatment initiation, baseline lung function and white blood cell indices as candidate predictors, using severe exacerbation risk and differential response across biologic agents as primary outcomes. Routinely available metrics differentiated subgroups with distinct response profiles and linked individual clinical parameters to heterogeneous biologic response in children.

Reduced baseline lung function was the strongest correlate of poorer response: lower FEV1 associated with higher residual exacerbation risk and smaller symptom gains on biologic therapy. Elevated systemic inflammation—specifically higher absolute white blood cell counts—clustered with nonresponse and more breakthrough attacks. Age and sex contributed smaller, additive effects. In rank order, reduced FEV1, elevated absolute white blood cell count, then age/sex patterns identified children at higher risk of biologic nonresponse.

Eosinophil counts and fractional exhaled nitric oxide (FeNO) aligned with some treatment effects, but single biomarkers often lacked adequate discrimination alone. Combining these biomarkers with the clinical parameter set improved stratification, producing clearer separation of likely responders versus nonresponders and supporting integrated risk models over reliance on a single laboratory measure.

Operationally, applying these predictors could prompt earlier specialist referral, closer objective monitoring of lung function and inflammatory indices, and consideration of alternative or adjunctive strategies for flagged patients. Implementation might include defined follow-up intervals and threshold-based reassessment tailored to individual risk profiles, enabling earlier detection of suboptimal response and potential reduction in preventable exacerbations.