What is the initial treatment for patients with ANCA (Antineutrophil Cytoplasmic Antibody) 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 Options

First-Line Regimens

1. Rituximab-based regimen:

   • Rituximab 375 mg/m²/week × 4 weeks 2, 1
   • Plus glucocorticoids (standard weight-based dosing)

2. Cyclophosphamide-based regimen:

   • Oral cyclophosphamide: 2 mg/kg/day for 3 months (continue for ongoing activity to maximum of 6 months) 2
   • IV cyclophosphamide: 15 mg/kg at weeks 0,2,4,7,10,13 (and weeks 16,19,21,24 if required) 2
   • Plus glucocorticoids

3. Combination therapy for severe disease:

   • Rituximab 375 mg/m²/week × 4 weeks
   • Plus IV cyclophosphamide 15 mg/kg at weeks 0 and 2 2, 1
   • Recommended for patients with serum creatinine >4 mg/dL, rapidly progressive renal disease, or diffuse alveolar hemorrhage requiring mechanical ventilation 1

Dose Adjustments for Cyclophosphamide

• Age-based adjustments: 2, 1

  • 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)

• Renal function adjustments: 2, 1

  • GFR <30 mL/min/1.73m²: reduce by 0.5 mg/kg/day (oral) or 2.5 mg/kg (IV)

Glucocorticoid Regimens

1. Standard regimen:

   • Weight-based dosing per PEXIVAS trial
   • Starting at 60 mg prednisolone, tapering to 5 mg by week 19-20 1
   • Adjust for weight (<50 kg or >75 kg)

2. Reduced-dose option:

   • Consider reduced-dose glucocorticoid regimen (0.5 mg/kg/day) with rituximab
   • Shown to be non-inferior to high-dose regimen (1 mg/kg/day) for remission induction with fewer serious adverse events and infections 3

3. Glucocorticoid alternative:

   • Avacopan (30 mg twice daily) may be considered as an alternative to glucocorticoids 2, 1
   • Particularly beneficial in patients with high risk of glucocorticoid toxicity or lower GFR who may benefit from greater renal recovery 1

Special Considerations

Plasma Exchange

• Consider plasma exchange for patients with: 2
  • 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

Infection Prophylaxis

• Provide prophylaxis against Pneumocystis jirovecii pneumonia with trimethoprim/sulfamethoxazole (800/160 mg on alternate days or 400/80 mg daily) for all patients receiving cyclophosphamide 2
• Alternative options for those with contraindications include dapsone, pentamidine, or atovaquone 2

Maintenance Therapy After Remission

After achieving remission, maintenance therapy is essential with either:

1. Rituximab-based maintenance:

   • Option 1: 500 mg × 2 at complete remission, and 500 mg at months 6,12, and 18 (MAINRITSAN scheme) 2, 1
   • Option 2: 1000 mg infusion after remission, and at months 4,8,12, and 16 (RITAZAREM scheme) 2, 1

2. Azathioprine-based maintenance:

   • 1.5-2 mg/kg/day at complete remission 2
   • Until 1 year after diagnosis, then decrease by 25 mg every 3 months 2
   • Plus low-dose glucocorticoids

3. Maintenance duration:

   • Optimal duration is between 18 months and 4 years after induction of remission 2, 1
   • Regular assessment of disease activity, B cell counts, and ANCA status is essential during maintenance therapy 1

Common Pitfalls and Caveats

1. Inadequate initial immunosuppression increases the risk of organ damage and mortality 1

2. Excessive glucocorticoid exposure should be minimized by considering reduced-dose regimens or avacopan 1, 3

3. Delayed recognition of treatment failure can lead to poor outcomes; regular assessment of disease activity is necessary to modify treatment if inadequate response within 4-6 weeks 1

4. Overlooking infection prophylaxis, especially for Pneumocystis jirovecii pneumonia, can increase the risk of complications during induction 1

5. Stopping maintenance therapy too early can lead to relapses, which can occur at a median of 34.4 months after the last rituximab infusion, especially in PR3-ANCA positive patients 1

6. ANCA titer changes, such as rising ANCA titers or conversion from negative to positive, can predict relapse and inform treatment decisions, but should not guide maintenance therapy decisions alone 1

By following these evidence-based recommendations, clinicians can optimize outcomes for patients with ANCA-associated vasculitis while minimizing treatment-related complications.