What is the role of Anti-IL5 (Interleukin-5) therapy, such as mepolizumab (mepolizumab), in the treatment of Eosinophilic Granulomatosis with Polyangiitis (EGPA)?

Role of Anti-IL5 Therapy in Eosinophilic Granulomatosis with Polyangiitis (EGPA)

Mepolizumab is strongly recommended as an effective therapy for relapsing-refractory EGPA without organ- or life-threatening manifestations, particularly for controlling respiratory manifestations and reducing glucocorticoid dependence. 1

Patient Selection for Anti-IL5 Therapy

Anti-IL5 therapy with mepolizumab is indicated in two main clinical scenarios:

1. Relapsing-refractory EGPA without organ- or life-threatening manifestations:

   • For patients who continue to have disease activity despite appropriate remission-induction therapy
   • Particularly effective for controlling respiratory manifestations (asthma and ENT involvement)
   • Allows for significant glucocorticoid sparing 1

2. Remission maintenance:

   • Especially beneficial for patients requiring ≥7.5 mg daily prednisone for control of respiratory manifestations
   • Helps reduce long-term glucocorticoid exposure 1

Dosing Recommendations

• FDA-approved dose: 300 mg subcutaneously every 4 weeks 2
• Alternative dosing consideration:
  • A lower initial dosage (100 mg every 4 weeks) can be considered for patients with limited respiratory manifestations
  • This lower dose can subsequently be titrated up to 300 mg every 4 weeks if response is unsatisfactory 1, 3

Efficacy and Outcomes

Mepolizumab has demonstrated effectiveness in:

• Inducing and maintaining remission in patients with relapsing or refractory EGPA
• Improving lung function
• Allowing glucocorticoid sparing - up to 69.6% of patients can reduce their daily dose by 75%, with 28.3% able to discontinue corticosteroids completely 4
• Reducing blood eosinophil counts - achieves approximately 83% reduction compared to placebo 2
• Preventing relapses - extends relapse-free periods 5

Treatment Algorithm for EGPA

1. Initial assessment:

   • Determine disease severity using the Five-Factor Score (FFS)
   • Obtain echocardiogram to assess cardiac involvement 6

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

   • High-dose glucocorticoids plus cyclophosphamide or rituximab for remission induction 6
   • Anti-IL5 therapy is not the first-line treatment in this scenario

3. For non-severe EGPA:

   • Glucocorticoids alone or with mepolizumab for induction 6
   • Maintenance with glucocorticoids alone or with mepolizumab

4. For refractory disease:

   • If systemic manifestations persist despite high-dose glucocorticoids plus cyclophosphamide, consider rituximab 1
   • If respiratory manifestations (asthma/ENT) persist without systemic involvement, add mepolizumab 1
   • For patients with disease refractory to mepolizumab, consider other anti-IL5 agents such as benralizumab 6, 4

5. Optimization of therapy:

   • Combine anti-IL5 therapy with optimized inhaled/topical therapies for respiratory manifestations
   • Involve specialists (pulmonologists, otolaryngologists) in management 1
   • Monitor disease activity using validated tools (e.g., BVAS)
   • Target glucocorticoid reduction to ≤4 mg/day of prednisone or equivalent 6

Important Clinical Considerations

• Timing of response: Pharmacodynamic effects (blood eosinophil reduction) typically occur within 4 weeks of treatment initiation 2

• Monitoring:

  • Blood eosinophil counts
  • Disease activity using validated tools
  • Glucocorticoid reduction capability
  • Potential hypersensitivity reactions after administration 6

• Alternative anti-IL5 options:

  • Benralizumab (30 mg subcutaneously every 4 weeks) may be considered for patients with EGPA refractory to mepolizumab 6, 4
  • Real-world data suggest comparable efficacy between benralizumab and mepolizumab, with benralizumab showing slightly higher remission rates at 24 months (69.2% vs 43.5%) 4

Pitfalls and Caveats

• Anti-IL5 therapy is not appropriate as first-line treatment for patients with organ- or life-threatening manifestations of EGPA
• Distinguish between persistent systemic manifestations versus persistent respiratory manifestations when evaluating treatment response
• Before labeling a patient as having refractory disease, ensure:
  • Primary diagnosis has been re-evaluated
  • Other etiologies (infections, malignancies) have been excluded
  • Appropriate remission-induction treatment has been used
  • Patient compliance has been assessed
  • Active manifestations are distinguished from irreversible damage 1
• Long-term safety and efficacy data beyond 24 months are still being established 7