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

Initial Treatment for ANCA-Associated Vasculitis

Glucocorticoids in combination with rituximab or cyclophosphamide are the recommended initial treatment for ANCA-associated vasculitis. 1

Treatment Algorithm

First-Line Induction Therapy Options:

1. Rituximab-based regimen:

   • Rituximab 375 mg/m²/week × 4 weeks
   • Plus glucocorticoids (weight-based tapering regimen)

2. Cyclophosphamide-based regimen:

   • Oral cyclophosphamide 2 mg/kg/day for 3 months (continue for ongoing activity up to 6 months)
   • OR IV cyclophosphamide 15 mg/kg at weeks 0,2,4,7,10,13
   • Plus glucocorticoids (weight-based tapering regimen)

3. Combination therapy for severe disease:

   • Rituximab 375 mg/m²/week × 4 weeks
   • PLUS IV cyclophosphamide 15 mg/kg at weeks 0 and 2
   • Plus glucocorticoids

Factors to Consider When Choosing Between Rituximab and Cyclophosphamide:

Cyclophosphamide preferred for:

• Severe glomerulonephritis (serum creatinine >4 mg/dL [354 μmol/L]) 1
• Rapidly progressive renal disease

Rituximab preferred for:

• Patients desiring to preserve fertility
• Patients with high risk of cyclophosphamide toxicity
• Relapsing disease

Glucocorticoid Regimens

Standard Weight-Based Tapering:

Based on PEXIVAS trial reduced-dose regimen 1:

Week	<50 kg	50-75 kg	>75 kg
1	50 mg	60 mg	75 mg
2	25 mg	30 mg	40 mg
3-4	20 mg	25 mg	30 mg
5-6	15 mg	20 mg	25 mg
7-8	12.5 mg	15 mg	20 mg
9-10	10 mg	12.5 mg	15 mg
11-12	7.5 mg	10 mg	12.5 mg
13-14	6 mg	7.5 mg	10 mg
15-16	5 mg	5 mg	7.5 mg
17-52	5 mg	5 mg	5 mg

Alternative to Glucocorticoids:

• Avacopan 30 mg twice daily can be used as an alternative to glucocorticoids, particularly in patients with high risk of glucocorticoid toxicity or lower GFR 1, 2

Additional Treatments

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 1, 2

Infection Prophylaxis:

• Trimethoprim/sulfamethoxazole (800/160 mg on alternate days or 400/80 mg daily) for all patients receiving cyclophosphamide 1, 2
• Alternative options for those with contraindications: dapsone, pentamidine, or atovaquone 1

Maintenance Therapy

After achieving remission, transition to maintenance therapy with:

1. Rituximab-based maintenance:

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

2. Azathioprine-based maintenance:

   • 1.5-2 mg/kg/day at complete remission until 1 year after diagnosis
   • Then decrease by 25 mg every 3 months

3. Duration of maintenance therapy:

   • Between 18 months and 4 years after induction of remission 1
   • Consider longer duration for PR3-ANCA positive patients due to higher relapse risk

Monitoring During Treatment

• Regular assessment of disease activity
• Monitor B cell counts if using rituximab
• Monitor ANCA titers - persistence of ANCA positivity, increase in levels, or conversion from negative to positive may predict relapse 1
• Monitor kidney function and proteinuria
• Monitor for adverse effects of immunosuppression

Common Pitfalls to Avoid

1. Inadequate initial immunosuppression - can increase risk of organ damage and mortality
2. Excessive glucocorticoid exposure - consider reduced-dose regimens or avacopan
3. Delayed recognition of treatment failure - modify treatment if inadequate response within 4-6 weeks
4. Overlooking infection prophylaxis - especially Pneumocystis jirovecii pneumonia prophylaxis
5. Stopping maintenance therapy too early - particularly risky in PR3-ANCA positive patients

Special Considerations

• Recent evidence shows that reduced-dose glucocorticoid regimens (0.5 mg/kg/day) with rituximab can be as effective as high-dose regimens (1 mg/kg/day) with fewer adverse events, particularly in patients without severe glomerulonephritis or alveolar hemorrhage 3
• Combination therapy with rituximab and low-dose cyclophosphamide has shown promising results with high remission rates and allows for rapid tapering of glucocorticoids 4
• For relapsing disease, rituximab is preferred over cyclophosphamide 1, 2