What is the treatment for Eosinophilic Granulomatosis with Polyangiitis (EGPA)?

Treatment of Eosinophilic Granulomatosis with Polyangiitis (EGPA)

For EGPA treatment, glucocorticoids are the initial therapy for all patients with new-onset active disease, with additional immunosuppressants (cyclophosphamide or rituximab) required for severe cases, while non-severe cases may be treated with glucocorticoids alone or in combination with mepolizumab. 1, 2

Disease Severity Assessment

Treatment decisions should be based on disease severity:

Severe EGPA (any of the following):

• Five-Factor Score (FFS) ≥1
• Presence of peripheral neuropathy
• Alveolar hemorrhage
• Other organ- or life-threatening manifestations (renal insufficiency, proteinuria, cardiomyopathy, gastrointestinal involvement, central nervous system involvement)

Non-severe EGPA:

• FFS = 0
• Absence of peripheral neuropathy, alveolar hemorrhage, or other organ/life-threatening manifestations

Treatment Algorithm

1. Remission Induction

For Severe EGPA:

• First-line: High-dose glucocorticoids (often IV pulse followed by oral) PLUS either:
  • Cyclophosphamide OR
  • Rituximab (alternative to cyclophosphamide) 1

For Non-severe EGPA:

• First-line: Glucocorticoids alone
• Alternative: Glucocorticoids plus mepolizumab (especially for relapsing or refractory disease without organ-threatening manifestations) 1, 2

2. Remission Maintenance

For Severe EGPA:

• Glucocorticoids PLUS one of the following:
  • Rituximab
  • Mepolizumab (300 mg SC every 4 weeks)
  • Traditional DMARDs (azathioprine, methotrexate, or leflunomide) 1, 2

For Non-severe EGPA:

• Glucocorticoids alone (tapered to minimum effective dose)
• Glucocorticoids plus mepolizumab (especially if requiring ≥7.5mg prednisone daily for control of respiratory manifestations) 1

Management of Relapses

Severe Systemic Relapse:

• High-dose glucocorticoids plus cyclophosphamide or rituximab 1

Non-severe Systemic or Respiratory Relapse:

• Increase glucocorticoid dose and/or add mepolizumab
• Optimize inhaled/topical therapies for respiratory manifestations 1, 2

Refractory Disease Management

Refractory EGPA is defined as unchanged or increased disease activity after 4 weeks of appropriate remission-induction therapy 1.

• For refractory EGPA without organ-threatening manifestations: Mepolizumab (300 mg SC every 4 weeks) plus glucocorticoids 1, 3
• For predominantly respiratory manifestations: Consider benralizumab (30 mg SC every 4 weeks) if mepolizumab fails 2

Special Considerations

1. Respiratory/ENT involvement: Optimize topical and/or inhaled therapy with involvement of specialists (pulmonologists, otolaryngologists) 1

2. ANCA status: ANCA-positive patients (30-40% of EGPA cases, mostly MPO-ANCA) more frequently show features of vasculitis (glomerulonephritis, neuropathy, purpura), while ANCA-negative patients more frequently manifest cardiomyopathy and lung involvement 1

3. Glucocorticoid tapering: Aim to reduce to ≤7.5mg prednisone daily for remission definition, with a goal of ≤4mg daily when possible 1, 3

4. Monitoring: Regular assessment of disease activity using validated clinical tools rather than relying solely on laboratory parameters like eosinophil count or ANCA 1

Pitfalls and Caveats

1. Differentiating relapse types: Distinguish between systemic relapse (recurrence of vasculitis) and respiratory relapse (isolated exacerbation of asthma and ENT manifestations), as treatment approaches differ 1

2. Mepolizumab dosing: The recommended dose for EGPA (300 mg SC every 4 weeks) is higher than that used for severe asthma (100 mg) 2, 3

3. Limited evidence: Despite its widespread use, rituximab has not demonstrated superiority to conventional therapy in a recent randomized controlled trial 4

4. Long-term monitoring: Regular assessment for EGPA-related manifestations (lung function, cardiovascular events, neurological complications) and treatment-related comorbidities (infections, osteoporosis, cancer) is essential 1

5. Treatment resistance: Approximately half of patients treated with mepolizumab may still not achieve protocol-defined remission, highlighting the need for close monitoring and potential treatment adjustments 3