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

Initial Treatment for ANCA Vasculitis

For organ-threatening ANCA vasculitis, initiate remission induction with either rituximab (375 mg/m² weekly for 4 weeks) or cyclophosphamide (oral 2 mg/kg/day or IV 15 mg/kg at weeks 0,2,4,7,10,13) combined with glucocorticoids, with rituximab preferred for relapsing disease. 1, 2

Disease Severity Stratification

The treatment approach must be stratified based on disease severity and organ involvement:

Organ-Threatening Disease (Severe)

Defined by renal involvement with creatinine >3.4 mg/dL, dialysis requirement, rapidly progressive glomerulonephritis, or diffuse alveolar hemorrhage with hypoxemia 1, 3:

Immunosuppressive Options:

• Rituximab: 375 mg/m² weekly for 4 weeks 1, 2

  • Preferred for relapsing disease (67% remission vs 42% with cyclophosphamide) 2
  • Non-inferior to cyclophosphamide for new-onset disease 2
  • Preserves fertility better than cyclophosphamide 1

• Cyclophosphamide alternatives: 1

  • Oral: 2 mg/kg/day for 3 months (maximum 6 months if ongoing activity)
  • IV: 15 mg/kg at weeks 0,2,4,7,10,13
  • Age-based dose reductions required: 1
    • Age >60 years: reduce oral to 1.5 mg/kg/day or IV to 12.5 mg/kg
    • Age >70 years: reduce oral to 1.0 mg/kg/day or IV to 10 mg/kg
    • GFR <30 ml/min/1.73m²: reduce oral by 0.5 mg/kg/day or IV by 2.5 mg/kg

• Combination therapy: Rituximab 375 mg/m² weekly × 4 weeks with IV cyclophosphamide 15 mg/kg at weeks 0 and 2 allows rapid glucocorticoid tapering 1, 4

Non-Organ-Threatening Disease

For isolated cutaneous or limited disease without vital organ involvement 1, 3:

• Methotrexate: 15-25 mg/week plus glucocorticoids 1, 3

  • Contraindicated if GFR <60 ml/min/1.73m² 1

• Mycophenolate mofetil: 2000 mg/day (divided doses), may increase to 3000 mg/day for poor response 1

• Azathioprine: 1.5-2 mg/kg/day plus glucocorticoids 3

Glucocorticoid Regimen

Standard approach: 1

• Initial pulse methylprednisolone 1000 mg IV daily for 1-3 days (for severe disease)
• Followed by oral prednisone 1 mg/kg/day (maximum 80 mg/day)
• Target dose of 7.5-10 mg/day by 3 months 1
• Taper to 5-7.5 mg/day for maintenance 1

Glucocorticoid-sparing alternative:

• Avacopan: 30 mg twice daily as alternative to glucocorticoids in combination with rituximab or cyclophosphamide 1, 5
  • Superior for sustained remission at 52 weeks (65.7% vs 54.9% with prednisone taper) 5
  • Particularly beneficial for patients at high risk of glucocorticoid toxicity or those with lower GFR 1

Adjunctive Therapies

Plasma Exchange

Consider for: 1

• Serum creatinine >3.4 mg/dL (>300 μmol/L)
• Dialysis-dependent patients
• Rapidly increasing creatinine
• Diffuse alveolar hemorrhage with hypoxemia

Infection Prophylaxis

Mandatory for all patients receiving cyclophosphamide: 1

• Trimethoprim/sulfamethoxazole 800/160 mg on alternate days or 400/80 mg daily
• Alternatives if contraindicated: dapsone or atovaquone 1

Cyclophosphamide-Specific Precautions

• MESNA (2-mercaptoethanesulfonate sodium): oral or IV to prevent hemorrhagic cystitis 1
• High fluid intake on infusion days 1

Transition to Maintenance Therapy

After achieving remission (typically 3-6 months): 1

• Rituximab maintenance: 1

  • MAINRITSAN scheme: 500 mg × 2 at complete remission, then 500 mg at months 6,12, and 18
  • OR RITAZAREM scheme: 1000 mg at remission, then at months 4,8,12, and 16

• Azathioprine: 1.5-2 mg/kg/day with low-dose glucocorticoids (5-7.5 mg/day) 1

• Mycophenolate mofetil: 2000 mg/day (divided doses) as alternative to azathioprine 1

Duration of maintenance: 18 months to 4 years after induction of remission 1

Critical Monitoring Requirements

During induction: 1

• Complete blood count weekly
• Dose adjustment or discontinuation if leucopenia develops
• Renal function and urinalysis regularly

Common pitfall: Failure to adjust cyclophosphamide doses for age and renal function increases toxicity risk without improving efficacy 1