Treatment of Eosinophilic Granulomatosis with Polyangiitis (EGPA)
Treatment for EGPA must be stratified by disease severity: patients with severe disease (Five-Factor Score ≥1, peripheral neuropathy, alveolar hemorrhage, or organ-threatening manifestations) require glucocorticoids plus cyclophosphamide or rituximab, while those with non-severe disease can be treated with glucocorticoids alone. 1
Initial Remission Induction Strategy
Severe Disease (FFS ≥1 or Organ-Threatening Features)
Start with pulsed intravenous methylprednisolone 500-1,000 mg daily for 3 days (maximum 3g total), followed by high-dose oral glucocorticoids at 0.75-1 mg/kg/day. 1
Add cyclophosphamide OR rituximab to glucocorticoids for all severe cases: 1, 2
- Cyclophosphamide: 0.6 g/m² intravenous pulses every 2 weeks for 1 month, then every 4 weeks until remission (typically 6 months; up to 9-12 months if slow response) 1
- Rituximab (alternative): 1-gram infusions given 2 weeks apart 1
- The REOVAS trial demonstrated rituximab is comparable to cyclophosphamide for remission induction in FFS ≥1 patients, with similar adverse events and no difference in response between ANCA-positive and ANCA-negative patients 1
Severe disease features requiring aggressive treatment include: 1
- Renal insufficiency (creatinine >1.58 mg/dL)
- Proteinuria >1 g/day
- Cardiomyopathy
- Gastrointestinal involvement
- CNS involvement
- Peripheral neuropathy
- Alveolar hemorrhage
- Mesenteric ischemia
- Central retinal artery/vein occlusion
Non-Severe Disease (FFS = 0, No Organ-Threatening Features)
Glucocorticoids alone are sufficient, achieving 93% remission rates. 1 However, 35% of patients experience early relapses within the first year, predominantly respiratory manifestations. 1
Consider adding mepolizumab to glucocorticoids for non-severe disease based on the MIRRA trial, which demonstrated superior remission rates (BVAS=0 and prednisolone ≤4 mg/day) compared to placebo. 1, 3
Remission Maintenance Therapy
Severe EGPA Maintenance
Use rituximab, mepolizumab, or traditional DMARDs (azathioprine, methotrexate) in combination with glucocorticoids, tapered to minimum effective dose. 1, 4
Non-Severe EGPA Maintenance
Glucocorticoids alone or combined with mepolizumab are recommended, with aggressive tapering to reduce toxicity. 1, 4
Target prednisone dose ≤7.5 mg/day for remission definition. 1
Mepolizumab Dosing and Indications
FDA-approved dose for EGPA is 300 mg subcutaneously every 4 weeks (administered as three separate 100-mg injections at least 5 cm apart). 4
Mepolizumab is specifically recommended for: 1, 3
- Relapsing-refractory EGPA without organ/life-threatening manifestations
- Remission maintenance, particularly when prednisone ≥7.5 mg/day is required for respiratory control
- Glucocorticoid-sparing strategy
Real-world evidence suggests 100 mg every 4 weeks may be effective for predominantly respiratory manifestations, though the 300 mg dose remains the approved standard. 5, 6 The lower dose achieved comparable complete response rates (35.7% at 24 months) with significant reductions in BVAS scores, prednisone requirements, and asthma exacerbations. 5
Management of Relapses
Severe Systemic Relapses
Use rituximab or cyclophosphamide with glucocorticoids. 1
Non-Severe Systemic and Respiratory Relapses
Increase glucocorticoid dose and/or add mepolizumab. 1
Distinguish systemic vasculitis relapses from isolated respiratory exacerbations (asthma/ENT), as treatment intensity differs. 1
Refractory Disease Management
Refractory EGPA is defined as unchanged or worsening disease after 4 weeks of appropriate therapy. 1
For refractory disease without organ-threatening features, mepolizumab 300 mg every 4 weeks combined with glucocorticoids is recommended. 1, 3
Respiratory Manifestations
Optimize inhaled glucocorticoids and long-acting β2-agonists for asthma control in all patients. 1, 2
Involve pulmonologists and otolaryngologists for comprehensive management of asthma and ENT manifestations. 1, 2
Special Considerations
ANCA status (positive vs. negative) does not necessitate different treatment approaches, though ANCA-positive patients may show slightly better responses to rituximab in observational studies. 1, 7 The REOVAS trial found no significant difference. 1
For cardiac involvement refractory to standard immunosuppression, high-dose IVIG (2 g/kg every 4 weeks) may be considered as salvage therapy. 3
Monitoring Requirements
Assess disease activity using validated clinical tools (BVAS), not laboratory parameters alone, as eosinophil counts and ANCA are unreliable biomarkers. 1
Monitor routinely for: 1
- Lung function
- Cardiovascular complications
- Neurological status
- Treatment-related complications (infections, osteoporosis, malignancy)
Common pitfall: Relying solely on eosinophil counts to guide therapy—clinical assessment is paramount. 1