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 be glucocorticoids in combination with rituximab or cyclophosphamide as induction therapy to achieve disease remission. 1

Induction Therapy Algorithm

Step 1: Choose the immunosuppressive agent

• First-line options:
  • Rituximab: 375 mg/m²/week × 4 weeks
  • Cyclophosphamide: Either oral (2 mg/kg/day) or intravenous (15 mg/kg at weeks 0,2,4,7,10,13)
  • Combination: Rituximab with 2 doses of IV cyclophosphamide (for severe disease)

Factors favoring cyclophosphamide:

• Severe glomerulonephritis (serum creatinine >4 mg/dL)
• Rapidly progressive renal disease
• Diffuse alveolar hemorrhage requiring mechanical ventilation

Factors favoring rituximab:

• Desire to preserve fertility
• Previous high cumulative cyclophosphamide exposure
• Relapsing disease

Step 2: Add glucocorticoids

• Standard regimen: Weight-based dosing per PEXIVAS trial
  • For 50-75 kg patient: Start at 60 mg prednisolone, taper to 5 mg by week 19-20
  • Adjust for weight (<50 kg or >75 kg)
• OR
• Consider avacopan (30 mg twice daily) as alternative to glucocorticoids in patients with:
  • High risk of glucocorticoid toxicity
  • Lower GFR who may benefit from greater renal recovery 1, 2

Step 3: Consider plasma exchange

• Add for patients with:
  • Serum creatinine >3.4 mg/dL (>300 μmol/L)
  • Patients requiring dialysis
  • Rapidly increasing serum creatinine
  • Diffuse alveolar hemorrhage with hypoxemia 1

Dosing Adjustments

Cyclophosphamide dose reductions:

• Age >60 years: Reduce to 1.5 mg/kg/day (oral) or 12.5 mg/kg (IV)
• Age >70 years: Reduce to 1.0 mg/kg/day (oral) or 10 mg/kg (IV)
• GFR <30 mL/min/1.73m²: Reduce by 0.5 mg/kg/day (oral) or 2.5 mg/kg (IV) 1

Mycophenolate mofetil (MMF) alternative:

• 2000 mg/day in divided doses
• May increase to 3000 mg/day for poor treatment response 1

Recent Evidence on Glucocorticoid Dosing

Recent research demonstrates that reduced-dose glucocorticoids (0.5 mg/kg/day prednisolone) plus rituximab is non-inferior to high-dose glucocorticoids (1 mg/kg/day) plus rituximab for remission induction at 6 months in patients without severe glomerulonephritis or alveolar hemorrhage 3. The reduced-dose regimen resulted in:

• Similar remission rates (71.0% vs 69.2%)
• Fewer serious adverse events (18.8% vs 36.9%)
• Fewer serious infections (7.2% vs 20.0%)

Maintenance Therapy After Induction

After achieving remission, maintenance therapy is essential:

• Recommended options:

  • Rituximab (preferred): Either 500 mg × 2 at remission and then at months 6,12,18 (MAINRITSAN scheme) OR 1000 mg at remission and months 4,8,12,16 (RITAZAREM scheme)
  • Azathioprine with low-dose glucocorticoids: 1.5-2 mg/kg/day 1, 2

• Optimal duration: 18 months to 4 years after induction of remission 1, 2

Common Pitfalls to Avoid

1. Inadequate initial immunosuppression: Insufficient treatment increases risk of organ damage and mortality.

2. Excessive glucocorticoid exposure: Consider reduced-dose regimens or avacopan to minimize toxicity.

3. Delayed recognition of treatment failure: Regularly assess disease activity and be prepared to modify treatment if inadequate response within 4-6 weeks.

4. Overlooking infection prophylaxis: Provide Pneumocystis jirovecii pneumonia prophylaxis during induction.

5. Stopping maintenance therapy too early: Premature discontinuation increases relapse risk, especially in PR3-ANCA positive patients.

6. Ignoring ANCA titer changes: Rising ANCA titers or conversion from negative to positive may predict relapse and should inform treatment decisions 1.

By following this evidence-based approach to initial treatment of ANCA-associated vasculitis, clinicians can optimize outcomes while minimizing treatment-related complications.