Maintenance Therapy for ANCA-Associated Vasculitis After Cyclophosphamide Induction
Either rituximab or azathioprine with low-dose glucocorticoids is recommended as maintenance therapy for patients with ANCA-associated vasculitis who were induced with cyclophosphamide. 1
First-Line Maintenance Options
Rituximab
- Dosing regimens:
- Option 1: 500 mg × 2 at complete remission, and 500 mg at months 6,12, and 18 (MAINRITSAN scheme)
- Option 2: 1000 mg infusion after induction, and at months 4,8,12, and 16 (RITAZAREM scheme) 1
- Advantages:
- Higher efficacy in preventing relapses, especially in PR3-ANCA positive patients
- Preferred for patients with history of relapse
- Avoids cumulative cyclophosphamide toxicity
Azathioprine
- Dosing: 1.5–2 mg/kg/day at complete remission until 1 year after diagnosis, then decrease by 25 mg every 3 months 1
- Advantages:
- Effective oral option
- May be preferred in patients with low baseline IgG (<300 mg/dl)
- Suitable when rituximab availability is limited
Glucocorticoids
- When using azathioprine, continue prednisolone at 5–7.5 mg/day for 2 years, then slowly reduce by 1 mg every 2 months 1
Duration of Maintenance Therapy
The optimal duration of maintenance therapy is between 18 months and 4 years after induction of remission 1. For high-risk patients (PR3-ANCA positive, history of relapse), consider extending therapy to 4 years.
Alternative Maintenance Options
Mycophenolate Mofetil (MMF)
- Dosing: 2000 mg/day (divided doses) at complete remission for 2 years 1
- Indication: Consider for patients intolerant of azathioprine
- Caution: Less effective than azathioprine for maintaining remission 2
Methotrexate
- Consider as alternative to azathioprine for maintenance in patients intolerant to azathioprine
- Contraindication: Do not use if GFR <60 ml/min per 1.73 m² 1
Factors Affecting Maintenance Therapy Choice
Factors Increasing Relapse Risk
- PR3-ANCA positivity
- Diagnosis of granulomatosis with polyangiitis
- History of previous relapse
- ANCA positivity at end of induction
- Rising ANCA titers
- Ear, nose, and throat involvement 1
Monitoring During Maintenance
- Regular assessment of disease activity
- ANCA titers (though controversial for guiding therapy)
- Complete blood count
- Renal function
- Drug-specific toxicities
Special Considerations
- Renal Function: For patients with GFR <30 ml/min/1.73 m², dose adjustments may be required
- Cumulative Cyclophosphamide: Consider total lifetime exposure when selecting maintenance therapy; cumulative doses above 36g are associated with increased malignancy risk 1
- Hypogammaglobulinemia: Monitor immunoglobulin levels in patients on rituximab
Relapse Management
- For relapsing disease, rituximab is preferred for reinduction 1
- After reinduction, maintenance therapy should be continued or restarted
Conclusion
Maintenance therapy is essential after cyclophosphamide induction to prevent relapses in ANCA-associated vasculitis. The choice between rituximab and azathioprine should be based on patient-specific factors including ANCA type, relapse risk, and comorbidities. The duration of maintenance therapy should be tailored according to relapse risk, with most patients requiring 18 months to 4 years of treatment.