What is the recommended management for a patient with moderate to severe vasculitis, such as granulomatosis with polyangiitis or microscopic polyangiitis?

Management of Moderate to Severe Vasculitis

For moderate to severe ANCA-associated vasculitis (granulomatosis with polyangiitis or microscopic polyangiitis), initiate remission induction with either rituximab or cyclophosphamide combined with high-dose glucocorticoids, followed by maintenance therapy with azathioprine, rituximab, or methotrexate for at least 24 months. 1

Remission Induction Therapy

First-Line Treatment Options

• Rituximab 375 mg/m² intravenously once weekly for 4 weeks is equally effective to cyclophosphamide for inducing remission in severe GPA/MPA, with 64% achieving complete remission at 6 months 2
• Cyclophosphamide (oral 2 mg/kg/day or intravenous pulses) combined with glucocorticoids remains a standard option for generalized disease 1
• Both rituximab and cyclophosphamide have equivalent efficacy for remission induction in organ-threatening or life-threatening disease 1

Glucocorticoid Regimen

• Administer methylprednisolone 1,000 mg intravenously daily for 1-3 days prior to initiating rituximab or cyclophosphamide 1, 2
• Follow with oral prednisone 1 mg/kg/day (maximum 80 mg/day) with rapid tapering 2
• A reduced-dose glucocorticoid regimen with more rapid taper is strongly recommended to minimize serious infections while maintaining efficacy 1

Plasma Exchange Considerations

• Add plasma exchange for patients with rapidly progressive glomerulonephritis requiring dialysis or at high risk of end-stage kidney disease (approximately 16% absolute risk reduction in ESKD) 1
• Plasma exchange provides moderate-high certainty benefit for severe renal disease but increases serious infection risk by approximately 8.5% 1
• For isolated pulmonary hemorrhage without renal involvement, plasma exchange is not recommended 1

Less Severe Disease

• For non-organ-threatening or non-life-threatening disease, methotrexate (15-25 mg/week oral or parenteral) combined with glucocorticoids is a less toxic alternative to cyclophosphamide 1

Remission Maintenance Therapy

Standard Maintenance Options

• Azathioprine 2 mg/kg/day is the preferred first-line maintenance agent (Level 1B evidence for GPA/MPA) 1
• Rituximab 500 mg intravenously every 6 months after initial two doses separated by 2 weeks 1, 2
• Methotrexate 20-25 mg/week (if creatinine <150 μmol/L) 1
• Mycophenolate mofetil as an alternative option 1

Duration and Monitoring

• Continue maintenance therapy for at least 24 months following achievement of sustained remission 1
• All maintenance regimens should include low-dose glucocorticoids during the maintenance phase 1
• Base treatment decisions on structured clinical assessment rather than ANCA titers alone 1

Refractory Disease Management

• For patients failing initial therapy, switch from cyclophosphamide to rituximab or vice versa 1
• Refer refractory patients to expert centers for evaluation and potential enrollment in clinical trials 1
• IVIG (2 g/kg divided over 5 days) may be considered for patients unable to receive standard immunomodulatory therapy, though it is less effective than rituximab or cyclophosphamide 3

Critical Safety Monitoring

Cyclophosphamide-Related Risks

• Investigate all persistent unexplained hematuria in patients with prior cyclophosphamide exposure due to bladder cancer risk 1
• Bladder cancer can occur months to years after cyclophosphamide discontinuation, with tobacco smokers at particularly high risk 1
• Consider mesna for bladder protection, though it may not completely prevent toxicity 1

Rituximab-Related Monitoring

• Test serum immunoglobulin levels prior to each rituximab course and in patients with recurrent infections 1
• Hypogammaglobulinemia is a recognized complication requiring monitoring 1

General Monitoring

• Assess cardiovascular risk periodically as patients with AAV have increased cardiovascular and cerebrovascular event risk 1
• Provide prophylaxis against Pneumocystis jiroveci pneumonia and osteoporosis during high-dose glucocorticoid therapy 1

Expert Center Management

• All patients with AAV should be managed in close collaboration with or at centers of expertise due to disease unpredictability, long-term complications, and need for specialized monitoring 1
• Obtain tissue biopsy when feasible to confirm diagnosis, with renal biopsy having up to 91.5% diagnostic yield in GPA with renal involvement 1