Can Tezepelumab be used for Eosinophilic Granulomatosis with Polyangiitis (EGPA)?

Tezepelumab for EGPA: Current Evidence and Recommendations

Tezepelumab is not currently recommended as a first-line or standard therapy for eosinophilic granulomatosis with polyangiitis (EGPA), but it may be considered as an off-label option for patients with refractory EGPA-related asthma who have failed other approved therapies. 1, 2

Current Standard Therapies for EGPA

First-Line Treatments

• Glucocorticoids: Remain the cornerstone of initial therapy for EGPA 3
• Disease severity stratification:
  • Severe EGPA (FFS ≥1 or organ/life-threatening manifestations): High-dose glucocorticoids plus cyclophosphamide or rituximab 3
  • Non-severe EGPA: Glucocorticoids alone or with mepolizumab 3

FDA-Approved Biologics for EGPA

• Mepolizumab: The only FDA-approved biologic for EGPA
  • Recommended dose: 300 mg subcutaneously every 4 weeks 4
  • Particularly effective for non-severe disease and respiratory manifestations 3
  • Proven efficacy in the MIRRA randomized controlled trial 3

Evidence for Tezepelumab in EGPA

The evidence supporting tezepelumab use in EGPA is extremely limited:

• Only case reports document its use in EGPA patients with refractory asthma 1, 2
• Tezepelumab is a monoclonal antibody that inhibits thymic stromal lymphopoietin (TSLP), targeting an upstream mechanism in the type 2 inflammatory pathway 1
• Preliminary findings suggest potential benefit in patients with severe refractory EGPA-related asthma who have failed previous treatments, including mepolizumab 2

Important Considerations and Concerns

• Persistent eosinophilia: Both reported cases showed persistent sputum eosinophilia despite clinical improvement, raising concerns about potential eosinophil rebound and related symptoms 1
• Limited evidence: No clinical trials have evaluated tezepelumab specifically for EGPA
• No guideline support: Current EGPA treatment guidelines do not mention tezepelumab 3, 4

Treatment Algorithm for EGPA

1. Initial assessment: Determine disease severity using Five-Factor Score (FFS) 3

   • Obtain echocardiogram at diagnosis 3

2. For severe EGPA (FFS ≥1 or organ/life-threatening manifestations):

   • High-dose glucocorticoids + cyclophosphamide or rituximab for induction 3
   • Maintenance: Rituximab, mepolizumab, or traditional DMARDs with glucocorticoids 3

3. For non-severe EGPA:

   • Glucocorticoids alone or with mepolizumab for induction 3
   • Maintenance: Glucocorticoids alone or with mepolizumab 3

4. For refractory disease:

   • Optimize inhaled/topical therapies for respiratory manifestations 3
   • For refractory asthma/ENT disease: Add mepolizumab (300 mg every 4 weeks) 3, 4
   • For patients failing mepolizumab: Consider rituximab (if systemic manifestations) 3

5. For patients with refractory asthma who have failed mepolizumab:

   • Tezepelumab could be considered as an off-label, last-resort option 1, 2
   • Close monitoring for persistent eosinophilia and potential rebound effects is essential 1

Conclusion

While tezepelumab shows preliminary promise for refractory EGPA-related asthma in isolated case reports, it is not currently recommended in treatment guidelines. Mepolizumab remains the only FDA-approved biologic for EGPA, with substantial evidence supporting its efficacy. Patients with EGPA should first receive standard therapies based on disease severity before considering experimental options like tezepelumab.