Treatment of Vasculitis
For ANCA-associated vasculitis with organ-threatening disease, initiate remission induction with rituximab (preferred) or cyclophosphamide combined with high-dose glucocorticoids, followed by maintenance therapy with rituximab for 24-48 months. 1, 2
Remission Induction Strategy
Organ-Threatening or Life-Threatening Disease (GPA/MPA)
First-line options:
- Rituximab (375 mg/m² IV weekly × 4 weeks OR 1g IV at weeks 0 and 2) PLUS glucocorticoids 1, 2
- Cyclophosphamide (oral 2 mg/kg/day for 3 months OR IV 15 mg/kg at weeks 0,2,4,7,10,13) PLUS glucocorticoids 1
Rituximab is specifically preferred for relapsing disease over cyclophosphamide based on superior outcomes in the RAVE trial 1, 3. For severe glomerulonephritis (serum creatinine >4 mg/dL), cyclophosphamide remains preferred, though combining 2 IV cyclophosphamide pulses with rituximab is an acceptable alternative 1.
Non-Organ-Threatening Disease (GPA/MPA)
Methotrexate (15-25 mg/week) or mycophenolate mofetil (2000-3000 mg/day) combined with glucocorticoids 4, 2. Methotrexate requires normal renal function (creatinine <1.5 mg/dL) and may take longer to achieve remission, particularly with pulmonary involvement 4.
Glucocorticoid Dosing
Standard approach: Prednisolone 1 mg/kg/day (maximum 60-80 mg/day) for 1 month, then taper to 15 mg/day by 3 months and 5 mg/day by 6 months 4. Do not use alternate-day dosing as this increases relapse risk 5.
Reduced-dose approach: The LoVAS trial demonstrated that 0.5 mg/kg/day prednisolone is noninferior to 1 mg/kg/day when combined with rituximab, with fewer severe infections 1. However, this was studied primarily in Japanese patients with MPO-ANCA vasculitis, so broader applicability remains uncertain.
Glucocorticoid-sparing alternative: Avacopan 30 mg twice daily can replace glucocorticoids when combined with rituximab or cyclophosphamide, achieving noninferiority for remission while potentially improving kidney outcomes 1, 2. This excludes patients with eGFR <15 mL/min/1.73 m² or severe alveolar hemorrhage requiring mechanical ventilation.
Adjunctive Therapies
Plasma exchange: Consider for serum creatinine >300-500 µmol/L (3.4-5.7 mg/dL) due to rapidly progressive glomerulonephritis to improve renal survival 4, 2. The PEXIVAS trial showed benefit specifically for severe renal disease, though it does not improve overall mortality 4. Routine use for alveolar hemorrhage is not recommended 2.
Pneumocystis prophylaxis: Mandatory for all patients receiving cyclophosphamide—use trimethoprim-sulfamethoxazole 800/160 mg on alternate days or 400/80 mg daily 4.
Maintenance Therapy
Rituximab is the preferred maintenance agent over conventional immunosuppressants 1, 2. Dosing: 500 mg IV every 6 months or 1g IV every 4 months 1, 3.
Alternative agents (if rituximab unavailable or contraindicated):
- Azathioprine 2 mg/kg/day (strongest alternative evidence) 4
- Methotrexate 20-25 mg/week (requires creatinine <1.5 mg/dL) 4
- Mycophenolate mofetil 2000-3000 mg/day 2
Leflunomide 20-30 mg/day may be more effective than methotrexate but carries more adverse effects 4.
Duration: Continue maintenance therapy for 24-48 months following remission induction 6, 2. Longer duration should be considered for relapsing patients or those with PR3-ANCA positivity (higher relapse risk), balanced against immunosuppression risks 2.
Glucocorticoids during maintenance: Taper to ≤5 mg/day prednisolone by 6 months with rituximab induction; complete withdrawal by 6 months is possible 1. Recent real-world data shows low-dose glucocorticoids during maintenance do not reduce major relapse risk but increase damage accumulation and hospitalization 7.
Large Vessel Vasculitis (GCA/Takayasu)
Giant Cell Arteritis:
- Initiate prednisolone 1 mg/kg/day (maximum 60 mg/day) immediately upon clinical suspicion 5
- For visual symptoms: Consider IV methylprednisolone 1-3g total 5
- Tocilizumab is now standard as glucocorticoid-sparing agent 8, 9, 10
- Low-dose aspirin (75-150 mg/day) for all patients to reduce cardiovascular/cerebrovascular events 5
- Temporal artery biopsy should be performed but not delay treatment; remains diagnostic up to 1-2 weeks after starting glucocorticoids 5
Takayasu Arteritis:
- High-dose oral glucocorticoids preferred over IV pulse glucocorticoids for severe active disease 8
- Add conventional immunosuppressant (methotrexate, azathioprine) or biologic (tocilizumab, TNF inhibitor) for relapsing/refractory disease 5, 8
- Reconstructive surgery only during quiescent disease phase at expert centers 5
Relapse Management
Major relapse (organ-threatening): Treat as new disease with glucocorticoids plus rituximab or cyclophosphamide 11, 6, 3. Rituximab is preferred for relapsing disease based on superior RAVE trial outcomes 1, 11.
Minor relapse (non-severe): Increase or reinstitute immunosuppression with agents other than cyclophosphamide—increase glucocorticoids with or without azathioprine/MMF, or use methotrexate 11, 3.
Critical Monitoring and Prophylaxis
- Cyclophosphamide monitoring: Dose reduction required for age >60 years and GFR <30 mL/min/1.73 m² 1
- Rituximab monitoring: Check serum immunoglobulin levels before each course and with recurrent infections 6
- Bone protection: All patients on glucocorticoids require osteoporosis prophylaxis 4
- Cardiovascular risk: Periodic assessment recommended 6
- Bladder cancer surveillance: Investigate persistent unexplained hematuria in cyclophosphamide-exposed patients 6
Common Pitfalls
Do not delay treatment for temporal artery biopsy in suspected GCA—irreversible vision loss can occur 5. Avoid long-term cyclophosphamide for maintenance due to cumulative toxicity; switch to safer alternatives after remission induction 4. Do not rely on ANCA titers alone to guide treatment changes—use structured clinical assessment 6, 4. For patients on dialysis at 3 months without extrarenal manifestations, consider discontinuing immunosuppression 1.