What is the initial treatment for ANCA (Antineutrophil Cytoplasmic Antibodies) vasculitis?

Initial Treatment for ANCA-Associated Vasculitis

The initial treatment for ANCA-associated vasculitis should include glucocorticoids in combination with rituximab or cyclophosphamide as induction therapy to achieve disease remission. 1

First-Line Induction Therapy Options

Rituximab-Based Regimen

• Rituximab 375 mg/m²/week × 4 weeks plus glucocorticoids 2, 1
• Particularly effective for relapsing disease, with 67% remission rate compared to 42% with cyclophosphamide 3
• FDA-approved for GPA (Wegener's) and MPA, with demonstrated non-inferiority to cyclophosphamide 4

Cyclophosphamide-Based Regimen

• Oral cyclophosphamide: 2 mg/kg/day for 3 months (continue for ongoing activity up to 6 months) plus glucocorticoids 2
  • Age adjustments: Reduce to 1.5 mg/kg/day for age >60 years; 1.0 mg/kg/day for age >70 years
  • Renal function adjustments: Reduce by 0.5 mg/kg/day for GFR <30 mL/min/1.73m²
• IV cyclophosphamide: 15 mg/kg at weeks 0,2,4,7,10,13 plus glucocorticoids 2
  • Age adjustments: Reduce to 12.5 mg/kg for age >60 years; 10 mg/kg for age >70 years
  • Renal function adjustments: Reduce by 2.5 mg/kg for GFR <30 mL/min/1.73m²

Combination Therapy for Severe Disease

• Rituximab 375 mg/m²/week × 4 weeks PLUS IV cyclophosphamide 15 mg/kg at weeks 0 and 2 1, 5
• Indicated for patients with:
  • Serum creatinine >4 mg/dL
  • Rapidly progressive renal disease
  • Diffuse alveolar hemorrhage requiring mechanical ventilation 1, 5
• This combination approach has shown high efficacy with 84% complete remission by 5 months 5

Glucocorticoid Regimens

Standard Regimen

• Weight-based dosing starting at 60 mg prednisolone and tapering to 5 mg by week 19-20 1

Alternative Approaches

• Reduced-dose glucocorticoid regimens (0.5 mg/kg/day) can be considered with rituximab to minimize steroid toxicity 1
• Avacopan (30 mg twice daily) as an alternative to glucocorticoids, particularly in patients with:
  • High risk of glucocorticoid toxicity
  • Lower GFR (may benefit from greater GFR recovery) 2, 1, 6
  • Administered in combination with either rituximab or cyclophosphamide 2
  • Demonstrated superiority to prednisone for sustained remission at 52 weeks 6

Additional Considerations

Plasma Exchange

• Consider plasma exchange for patients with:
  • Serum creatinine >3.4 mg/dL (>300 mmol/L)
  • Patients requiring dialysis or with rapidly increasing serum creatinine
  • Patients with diffuse alveolar hemorrhage who have hypoxemia 2, 1

Infection Prophylaxis

• Prophylaxis against Pneumocystis jirovecii pneumonia is essential:
  • Trimethoprim/sulfamethoxazole 800/160 mg on alternate days or 400/80 mg daily
  • Alternative options for patients with contraindications: dapsone, pentamidine, or atovaquone 1

Common Pitfalls to Avoid

1. Inadequate initial immunosuppression increases the risk of organ damage and mortality 1
2. Delayed recognition of treatment failure can lead to poor outcomes; assess disease activity regularly and modify treatment if inadequate response within 4-6 weeks 1
3. Overlooking infection prophylaxis, particularly for Pneumocystis jirovecii pneumonia 1
4. Excessive glucocorticoid exposure should be minimized by considering reduced-dose regimens or avacopan 1
5. Stopping maintenance therapy too early can lead to relapses, especially in PR3-ANCA positive patients 1

Maintenance Therapy After Remission

Once remission is achieved, maintenance therapy should be initiated with either:

• Rituximab-based maintenance: 500 mg × 2 at complete remission, and 500 mg at months 6,12, and 18 2, 1
• Azathioprine-based maintenance: 1.5-2 mg/kg/day at complete remission until 1 year after diagnosis, then decreased by 25 mg every 3 months 2, 1
• Optimal duration of maintenance therapy is between 18 months and 4 years after induction of remission 2, 1

The initial treatment approach to ANCA-associated vasculitis has evolved significantly, with rituximab now established as an effective alternative to cyclophosphamide, particularly for relapsing disease. The combination of appropriate immunosuppression with careful monitoring and infection prophylaxis is essential for optimal outcomes.