Is Tezspire (tezepelumab) recommended as a first-line treatment for pediatric patients with severe asthma?

Tezepelumab in Pediatric Patients with Severe Asthma

Tezepelumab (Tezspire) is not recommended as a first-line treatment for pediatric patients with severe asthma. Inhaled corticosteroids (ICS) remain the preferred first-line controller therapy for pediatric patients with severe asthma, with step-up options including combination therapy with long-acting beta-agonists (LABAs) before considering biologics like tezepelumab.

Diagnosis and Initial Management of Pediatric Asthma

Before considering any treatment, proper diagnosis is essential:

• Diagnosis of asthma in children requires at least two abnormal objective test results 1:

  • Spirometry with bronchodilator reversibility (BDR) testing
  • Fractional exhaled nitric oxide (FeNO) measurement
  • Peak expiratory flow rate (PEFR) variability or challenge testing

• For children 5-16 years with severe asthma, the treatment approach follows a stepwise progression:

Step 1-2: Mild Persistent Asthma

• Low-dose ICS is the preferred first-line controller therapy 1
• Alternative options include leukotriene receptor antagonists (LTRAs) or cromolyn

Step 3: Moderate Persistent Asthma

• Preferred options 1:
  1. Low-dose ICS plus LABA
  2. Medium-dose ICS monotherapy

Step 4-6: Severe Persistent Asthma

• ICS-LABA combination is preferred 1
• For step 6, consider maintenance oral corticosteroids after confirming clinical reversibility

Role of Tezepelumab in Pediatric Asthma

Tezepelumab is a monoclonal antibody that blocks thymic stromal lymphopoietin (TSLP), an epithelial-derived cytokine implicated in asthma pathogenesis 2. While it has shown efficacy in severe asthma, its position in pediatric treatment is limited:

• Tezepelumab is approved as an add-on maintenance treatment for patients ≥12 years with severe asthma in the USA 2
• It should be considered only after failure of optimized standard therapy
• It is the only biologic approved for severe asthma without phenotype (eosinophilic or allergic) or biomarker limitations 2

Evidence for Tezepelumab Efficacy

The NAVIGATOR trial demonstrated that tezepelumab reduced exacerbations in patients with severe, uncontrolled asthma 3:

• 56% reduction in annualized exacerbation rate compared to placebo
• Improvements in FEV1 and asthma control scores
• Efficacy across both T2-high and T2-low asthma phenotypes 4
• Included adolescents (12-17 years) and adults

Treatment Algorithm for Pediatric Severe Asthma

1. First-line: Optimize ICS therapy (medium to high dose) with proper technique and adherence
2. Second-line: Add LABA to ICS therapy
3. Third-line: Consider adding additional controllers (LTRA, tiotropium)
4. Fourth-line: Consider biologics based on phenotype:
   • For patients ≥12 years with severe uncontrolled asthma despite optimized therapy, tezepelumab can be considered as add-on therapy

Important Considerations

• Monitor treatment response carefully; if benefits are sustained for 2-4 months, consider step-down therapy 1
• If no clear benefits within 4-6 weeks, consider alternative therapies or diagnoses 1
• For children with severe asthma, regular monitoring of lung function is essential to detect potential progressive worsening 1
• Growth should be monitored in children on high-dose ICS or multiple courses of oral corticosteroids 1

Pitfalls to Avoid

1. Inadequate diagnosis: Ensure proper objective testing before initiating any therapy
2. Skipping steps: Don't jump to biologics before optimizing standard therapies
3. Overlooking adherence: Poor adherence to ICS is common and should be addressed before escalating therapy
4. Ignoring comorbidities: Allergic rhinitis, GERD, and obesity can worsen asthma control
5. Relying solely on symptoms: The 2021 ERS guidelines recommend against diagnosing asthma based on symptom improvement alone after a trial of medication 1

In conclusion, while tezepelumab has demonstrated efficacy in patients ≥12 years with severe asthma, it should be reserved as an add-on therapy after failure of optimized standard treatments, not as a first-line option.