Treatment of Vasculitis
For ANCA-associated vasculitis (AAV), use rituximab or cyclophosphamide combined with reduced-dose glucocorticoids for remission induction, followed by maintenance therapy with rituximab or azathioprine plus low-dose glucocorticoids for 18 months to 4 years. 1
Remission Induction Therapy
The 2024 KDIGO guidelines provide the most current evidence-based approach for treating AAV (GPA, MPA, EGPA):
Immunosuppressive Options
Choose between:
- Rituximab: 375 mg/m² IV weekly × 4 weeks, OR 1,000 mg IV on days 1 and 15 1
- Cyclophosphamide:
Rituximab is preferred for relapsing disease 1 and has demonstrated non-inferiority to cyclophosphamide-azathioprine regimens with maintained remission rates of 39% at 18 months 2.
Glucocorticoid Dosing (Reduced-Dose Protocol)
The PEXIVAS trial established that reduced glucocorticoid dosing is as effective as standard dosing with fewer adverse effects 1:
Weight-based oral prednisolone taper:
- Week 1: 50-75 mg (based on <50 kg, 50-75 kg, >75 kg)
- Week 2: 25-40 mg
- Weeks 3-4: 20-30 mg
- Weeks 5-6: 15-25 mg
- Weeks 7-8: 12.5-20 mg
- Weeks 9-10: 10-15 mg
- Weeks 11-12: 7.5-12.5 mg
- Weeks 13-16: 5-10 mg
- Weeks 17-52: 5 mg
- After 52 weeks: taper per local practice 1
Alternative: Avacopan (30 mg twice daily) can replace glucocorticoids entirely when combined with rituximab or cyclophosphamide, particularly beneficial for patients at high risk of glucocorticoid toxicity or those with lower GFR 1.
Special Considerations for Severe Disease
Add plasma exchange for:
- Serum creatinine >3.4 mg/dL (>300 μmol/L)
- Dialysis requirement or rapidly rising creatinine
- Diffuse alveolar hemorrhage with hypoxemia 1
The evidence for plasma exchange remains conditional, as the PEXIVAS trial showed no mortality benefit, though it may aid kidney recovery in select patients 1.
Maintenance Therapy
After achieving remission, maintenance therapy is mandatory to prevent relapse 1.
First-Line Maintenance Options
Rituximab (preferred):
- 500 mg IV every 6 months (MAINRITSAN protocol), OR
- 1,000 mg IV at months 4,8,12, and 16 (RITAZAREM protocol) 1
Azathioprine (alternative):
- 1.5-2 mg/kg/day at complete remission
- Continue for 1 year, then decrease by 25 mg every 3 months
- For extended therapy: maintain 1.5-2 mg/kg/day for 18-24 months, then reduce to 1 mg/kg/day until 4 years, then taper by 25 mg every 3 months 1
Concurrent low-dose glucocorticoids:
- 5-7.5 mg/day for 2 years
- Then reduce by 1 mg every 2 months 1
Alternative Maintenance Agents
If azathioprine intolerant:
- Mycophenolate mofetil: 2,000 mg/day (divided doses) for 2 years 1
- Methotrexate: Up to 25 mg/week (avoid if GFR <60 mL/min/1.73 m²) 3, 1
Duration of Maintenance
Optimal duration: 18 months to 4 years after induction 1
Extend therapy toward 4 years for patients with high relapse risk:
- PR3-ANCA positivity
- Persistent ANCA positivity
- Lung involvement
- History of relapse 1
Management of Relapsing or Refractory Disease
For relapse: Re-induce with rituximab (preferred over cyclophosphamide if previously used) 1
For refractory disease:
- Increase glucocorticoids (IV or oral)
- Switch immunosuppressant: add rituximab if cyclophosphamide was used initially, or vice versa
- Consider plasma exchange 1
EGPA-Specific Considerations
The 2021 ACR/Vasculitis Foundation guidelines distinguish EGPA management 3:
Severe EGPA (organ-threatening): Cyclophosphamide or rituximab + glucocorticoids
Non-severe EGPA:
- Mepolizumab 300 mg SC every 4 weeks, OR
- Azathioprine, methotrexate, or mycophenolate mofetil 3
Critical Pitfalls to Avoid
Do not use methotrexate if GFR <60 mL/min/1.73 m² - risk of severe toxicity 1
Adjust cyclophosphamide doses for age and renal function - failure to reduce doses increases infection risk without added benefit 1
Do not stop maintenance therapy prematurely - most relapses occur within 2 years, but risk persists up to 4 years 1
Following rituximab induction, maintenance therapy is still required - B-cell reconstitution typically occurs by 18 months, necessitating ongoing immunosuppression 1, 2
Plasma exchange is not routinely indicated - reserve for severe renal disease or life-threatening alveolar hemorrhage 1
The 2024 KDIGO guidelines 1 represent the most comprehensive and recent evidence synthesis, superseding the 2021 ACR recommendations 3 for ANCA-associated vasculitis management. These recommendations prioritize reduced glucocorticoid exposure to minimize long-term morbidity while maintaining disease control through targeted immunosuppression.