Current Treatment of ANCA Vasculitis
For new-onset ANCA vasculitis, initiate induction therapy with glucocorticoids combined with either rituximab or cyclophosphamide, followed by maintenance therapy with rituximab (preferred) or azathioprine for 18 months to 4 years. 1
Induction Therapy
First-Line Regimen
- Glucocorticoids plus rituximab or cyclophosphamide are recommended for remission induction in new-onset disease 1
- Rituximab dosing: 375 mg/m² weekly for 4 weeks 1, 2
- Cyclophosphamide options: oral 2 mg/kg/day for 3 months OR intravenous 15 mg/kg at weeks 0,2,4,7,10,13 1
Choosing Between Rituximab and Cyclophosphamide
Prefer cyclophosphamide when:
- Severe glomerulonephritis with serum creatinine >4 mg/dL (>354 μmol/L) 1
- Consider combining 2 intravenous pulses of cyclophosphamide with rituximab in this severe presentation 1
Prefer rituximab when:
- Relapsing disease (rituximab achieved superior outcomes in this subgroup) 2, 3
- Women of childbearing age 4
- Concerns about malignancy risk 4
- PR3-ANCA positivity 5
Glucocorticoid Dosing
- Administer 1,000 mg intravenous methylprednisolone daily for 1-3 days prior to initial infusion 2
- Follow with oral prednisone 1 mg/kg/day (not exceeding 80 mg/day) with structured tapering 2
- Use the reduced-dose PEXIVAS protocol for weight-based tapering over 52 weeks, ending at 5 mg/day 1
Avacopan as Glucocorticoid Alternative
- Avacopan (30 mg twice daily) may replace glucocorticoids in patients at high risk of glucocorticoid toxicity 1
- Particularly beneficial for patients with GFR <30 mL/min/1.73 m² who may achieve greater GFR recovery 1
- Evidence quality is moderate for sustained remission but limited by study methodology concerns 1
Plasma Exchange Consideration
- Consider plasma exchange for serum creatinine >3.4 mg/dL, though this remains controversial with only 75% guideline approval 1
Maintenance Therapy
After Achieving Remission
Rituximab is the preferred maintenance agent 5, 6
Azathioprine is an acceptable alternative 1, 5
- Dosing: 1.5-2 mg/kg/day at complete remission, taper after 1 year 5, 6
- Continue for 2 years at complete remission 5
Concomitant Glucocorticoids During Maintenance
- Continue low-dose glucocorticoids at 5-7.5 mg/day for 2 years 5
- Reduce by 1 mg every 2 months thereafter 5
Alternative Maintenance Agents
- Mycophenolate mofetil 2000 mg/day for patients intolerant of azathioprine, continuing for 2 years 5
- Methotrexate is an alternative to azathioprine but contraindicated if GFR <60 mL/min/1.73 m² 5
Management of Relapsing Disease
Reinitiate induction therapy, preferably with rituximab 5, 6, 7
- Rituximab achieved >90% remission rates by 4 months in relapsing GPA/MPA patients 5
- In the RAVE trial, rituximab was superior to cyclophosphamide-azathioprine at 6 and 12 months specifically in relapsing disease 3
- Reintroduce or intensify glucocorticoids as bridge therapy 7
Supportive Care and Monitoring
Infection Prophylaxis
- Trimethoprim-sulfamethoxazole is mandatory for all patients receiving cyclophosphamide 6
- In GPA/MPA Study 1,62% of rituximab-treated patients experienced infections, with 11% serious infections 2
Bone Protection
- Calcium, vitamin D, and bisphosphonates for all patients on glucocorticoids 6
Monitoring Requirements
- Complete blood count weekly during induction 8
- Adjust cyclophosphamide dose for leucopenia <4000/μL 8
- Monitor ANCA levels: persistence, increase, or conversion from negative to positive predicts relapse risk 1
Critical Pitfalls to Avoid
- Do not use methotrexate if GFR <60 mL/min/1.73 m² 5
- Do not discontinue maintenance therapy prematurely—minimum 18 months required 5
- In severe renal disease (SCr >4 mg/dL), limited data support rituximab monotherapy; consider cyclophosphamide or combination therapy 1
- Hypogammaglobulinemia develops in 27-58% of rituximab-treated patients by 6 months; monitor immunoglobulin levels 2