Biologics in severe pediatric asthma: advances and unmet needs

ABSTRACT

Severe pediatric asthma is defined as asthma that remains uncontrolled despite adherence to optimized high-dose inhaled corticosteroids (ICS) with long-acting β2-agonists (LABA) and systematic management of modifiable factors, or that worsens upon treatment de-escalation. Affecting approximately 3% of European children, this condition imposes substantial clinical and socioeconomic burden due to frequent exacerbations, persistent symptoms, impaired lung function, and elevated healthcare utilization, emergency department visits and hospitalizations. Advances in the understanding of asthma immunopathology have enabled the development of targeted biologic therapies, including omalizumab, mepolizumab, benralizumab, dupilumab, and tezepelumab, which have improved disease control and reduced systemic corticosteroid requirements. These agents decrease exacerbation frequency, enhance lung function, and facilitate more individualized, biomarker-guided treatment strategies. Selection of therapy is guided by clinical phenotype, inflammatory endotype, and biomarkers such as blood eosinophil count, fractional exhaled nitric oxide (FeNO), and IgE levels. While therapeutic selection relies heavily on clinical phenotype and biomarker profiling, significant challenges persist, including high treatment costs, inequitable access, immunogenicity, and limited pediatric data to define remission, optimal treatment duration, and discontinuation strategies. Multidisciplinary, phenotype-driven care and long-term monitoring remain essential to maximize outcomes. Future research should focus on refining predictive biomarkers, expanding clinical trial diversity, and standardizing definitions of treatment success and remission to guide earlier, precision-based interventions in children with severe asthma.

IMPACT STATEMENT

Precision biologic therapy is redefining severe pediatric asthma, though durable remission strategies and validated biomarkers for treatment selection remain insufficiently defined.

KEY WORDS
Severe pediatric asthma; biologics; precision medicine.