What is the preferred biologic agent, Tezspire (tezepelumab) versus Nucala (mepolizumab) or Fasenra (benralizumab), for pediatric patients with severe persistent asthma who are failing standard of care therapy?

Tezepelumab (Tezspire) is the Preferred Biologic for Severe Persistent Pediatric Asthma Failing Standard Therapy

For pediatric patients with severe persistent asthma failing standard of care therapy, tezepelumab (Tezspire) is the preferred biologic agent over mepolizumab (Nucala) or benralizumab (Fasenra) due to its broader efficacy across multiple asthma phenotypes and pathways.

Rationale for Biologic Selection

Mechanism of Action Comparison

• Tezepelumab: Blocks thymic stromal lymphopoietin (TSLP), an upstream epithelial cytokine that affects multiple inflammatory pathways in asthma 1
• Mepolizumab: Targets IL-5 specifically, reducing eosinophilic inflammation 2
• Benralizumab: Targets IL-5 receptor, also primarily affecting eosinophilic inflammation 3

Efficacy Across Phenotypes

Tezepelumab demonstrates superior versatility:

• Reduces exacerbations by 63-71% in eosinophilic severe asthma
• Reduces exacerbations by 58-68% in allergic severe asthma
• Reduces exacerbations by 34-49% even in type 2-low asthma 1
• Effective across multiple phenotypes, unlike other biologics that target only specific inflammatory pathways

Age Considerations

• Tezepelumab is FDA-approved for patients ≥12 years with severe asthma 4
• Mepolizumab is approved for severe asthma with eosinophilic phenotype in children ≥6 years 2
• Most biologics are not approved for children <6 years 5

Patient Evaluation Before Initiating Biologic Therapy

Before starting any biologic, ensure:

1. Confirmation of severe persistent asthma diagnosis

2. Documentation of poor control despite maximal conventional therapy:

   • Adherence to high-dose inhaled corticosteroids plus long-acting β2-agonists
   • Multiple exacerbations despite appropriate therapy
   • Significant impact on quality of life 5

3. Phenotyping through biomarkers:

   • Blood eosinophil count
   • Total serum IgE levels
   • Fractional exhaled nitric oxide (FeNO)
   • Allergic sensitization testing 5

Decision Algorithm for Biologic Selection

1. First-line option: Tezepelumab

   • Preferred for most pediatric patients with severe asthma due to efficacy across phenotypes
   • Particularly valuable when phenotype is mixed or unclear
   • Demonstrated higher efficacy in reducing hospitalizations and emergency department visits 1

2. Alternative options based on specific phenotypes:

   • For predominantly allergic asthma with elevated IgE: Consider omalizumab
   • For clearly eosinophilic asthma with blood eosinophils ≥300 cells/μL: Consider mepolizumab or benralizumab 3, 6

Monitoring Response to Therapy

Evaluate response after at least 16 weeks of treatment by tracking:

• Exacerbation frequency
• Systemic corticosteroid use
• Symptom control
• Lung function
• Quality of life 5

Important Caveats

• All biologics require administration in a clinical setting with capacity to monitor and treat potential reactions 7
• Referral to a pediatric asthma specialist is strongly recommended before initiating any biologic therapy 5
• The comparative efficacy differences between biologics may be minimal compared to clinically important thresholds 6
• Long-term safety data in pediatric populations remains limited for newer biologics like tezepelumab

Conclusion

While all three biologics (tezepelumab, mepolizumab, and benralizumab) have demonstrated efficacy in reducing exacerbations in severe asthma, tezepelumab's unique mechanism targeting an upstream mediator provides broader efficacy across multiple asthma phenotypes, making it the preferred choice for pediatric patients with severe persistent asthma failing standard therapy.