What are the first-line biological therapy options for pediatric asthma patients with multiple trigger exacerbations?

First-Line Biological Therapy Options for Pediatric Asthma with Multiple Trigger Exacerbations

Omalizumab is the first-line biological therapy option for pediatric patients with severe allergic asthma experiencing multiple trigger exacerbations, particularly for those aged 6 years and older with elevated IgE levels and evidence of allergic sensitization.

Understanding Biological Therapy in Pediatric Asthma

Biological therapies target specific inflammatory pathways involved in asthma pathogenesis. In pediatric patients, the T2-high asthma endotype (characterized by eosinophilic airway inflammation and allergic sensitization driven by IgE, IL-4, IL-5, and IL-13) is most common 1. This understanding has guided the development of biological therapies for children with severe asthma.

Available Biological Options for Pediatric Patients

Omalizumab (Anti-IgE)

• FDA approved for: Children ≥6 years with moderate to severe persistent allergic asthma
• Mechanism: Humanized monoclonal antibody that binds to free IgE, blocking the allergic cascade 1
• Efficacy:
  • Reduces exacerbation rates by 72% and hospitalization rates by 88.5% in real-world studies 2
  • Improves asthma control from poor to good in 67% of children after 1 year of treatment 2
  • Particularly effective in patients with:
    • Low baseline lung function (FEV1 <90%)
    • Previous hospitalizations
    • Frequent baseline exacerbations (≥3 per year)
    • High baseline eosinophil count (≥300 cells/μL) 3

Mepolizumab (Anti-IL-5)

• FDA approved for: Children ≥6 years with severe asthma with an eosinophilic phenotype 4
• Mechanism: Humanized monoclonal antibody that targets IL-5, reducing eosinophilic inflammation
• Dosing: 40 mg subcutaneously every 4 weeks for children 6-11 years; 100 mg for those ≥12 years 4

Benralizumab (Anti-IL-5Rα)

• FDA approved for: Children ≥6 years with severe asthma with an eosinophilic phenotype 5
• Mechanism: Humanized monoclonal antibody that binds to IL-5 receptor alpha, causing eosinophil depletion
• Dosing: 10 mg subcutaneously for patients <35 kg and 30 mg for patients ≥35 kg every 4 weeks for the first 3 doses, then every 8 weeks thereafter 5

Decision Algorithm for Selecting First-Line Biological Therapy

1. Confirm severe asthma diagnosis and poor control despite maximal conventional therapy:

   • Verify adherence to high-dose inhaled corticosteroids (ICS) plus long-acting β2-agonists (LABAs)
   • Document multiple exacerbations (≥2 per year) requiring systemic corticosteroids
   • Assess impact on quality of life, school attendance, and daily activities

2. Determine asthma phenotype through biomarkers:

   • Measure total serum IgE levels
   • Check blood eosinophil count
   • Consider fractional exhaled nitric oxide (FeNO) testing
   • Confirm allergic sensitization through skin prick testing or specific IgE testing

3. Select biological therapy based on phenotype:

   • For allergic asthma with elevated IgE: Omalizumab is first-line
   • For eosinophilic non-allergic asthma: Consider anti-IL-5 therapies (mepolizumab or benralizumab)

Clinical Pearls and Pitfalls

• Timing of assessment: Evaluate response to biological therapy after at least 16 weeks of treatment
• Monitoring parameters: Track exacerbation frequency, systemic corticosteroid use, symptom control, lung function, and quality of life
• Long-term efficacy: Omalizumab has demonstrated sustained efficacy for up to 6 years in pediatric patients 6
• Common pitfall: Failing to verify allergic sensitization before initiating omalizumab
• Important consideration: The NIH asthma management guidelines did not address biological therapies in their 2020 update because at the time the decision was made (2014), only omalizumab was available 1

Special Considerations

• Age restrictions: Most biologics are approved for children ≥6 years; none are currently approved for children <6 years
• Pregnancy considerations: Limited data exists on the use of biologics during pregnancy, though animal studies show no teratogenic effects 5, 4
• Referral to specialist: Children with severe asthma being considered for biological therapy should be referred to a pediatric asthma specialist 7

Conclusion

For pediatric patients with severe allergic asthma and multiple trigger exacerbations, omalizumab has the most robust evidence and longest track record as a first-line biological therapy option. For children with predominantly eosinophilic inflammation, anti-IL-5 therapies like mepolizumab or benralizumab may be considered. The choice should be guided by the specific inflammatory phenotype, with careful monitoring of response to optimize outcomes related to morbidity, mortality, and quality of life.