What is the treatment for ANCA (Antineutrophil Cytoplasmic Antibody) vasculitis?

Treatment of ANCA-Associated Vasculitis

For organ-threatening or life-threatening ANCA vasculitis, initiate remission induction with glucocorticoids combined with rituximab (preferred) or cyclophosphamide, followed by maintenance therapy with rituximab for 24-48 months. 1

Disease Severity Classification and Initial Assessment

Before initiating treatment, classify disease severity to guide therapeutic intensity:

• Organ-threatening/life-threatening disease: Renal involvement with creatinine >300 µmol/L, diffuse alveolar hemorrhage, or other vital organ dysfunction requiring aggressive immunosuppression 1
• Non-organ-threatening disease: Active disease without immediate threat to organ function, allowing for less intensive regimens 1
• Obtain tissue biopsy (kidney, lung, or other affected tissue) when feasible to confirm pauci-immune vasculitis, though treatment should not be delayed in rapidly deteriorating patients 1
• Test for both PR3-ANCA and MPO-ANCA using high-quality antigen-specific assays as the primary diagnostic method 1

Remission Induction for Organ-Threatening Disease (GPA/MPA)

First-Line Therapy

Rituximab is preferred over cyclophosphamide for relapsing disease and PR3-ANCA positive patients. 1

Rituximab regimen:

• 375 mg/m² IV weekly for 4 weeks 1, 2
• Premedicate with antihistamine and acetaminophen before each infusion 2
• Achieved 64% complete remission at 6 months in clinical trials 2

Cyclophosphamide regimen (if rituximab unavailable or contraindicated):

• Oral: 2 mg/kg/day (maximum 200 mg/day) for 3-6 months 1
• IV pulse: 15 mg/kg at weeks 0,2,4,7,10,13 1
• Reduce dose by 0.5 mg/kg/day (oral) or 2.5 mg/kg (IV) if GFR <30 ml/min/1.73 m² 3
• Mandatory MESNA administration with IV cyclophosphamide to prevent hemorrhagic cystitis 1, 3
• Mandatory Pneumocystis jirovecii prophylaxis with trimethoprim/sulfamethoxazole 800/160 mg on alternate days or 400/80 mg daily 1, 4

Glucocorticoid Dosing

Start with oral prednisolone 50-75 mg/day (based on body weight), tapering to 5 mg/day by 4-5 months according to a structured schedule. 1

• May give 1-3 days of IV methylprednisolone 1000 mg/day for severe disease before oral therapy 2
• Recent evidence supports reduced-dose regimens (0.5 mg/kg/day) with similar efficacy and fewer adverse effects compared to traditional high-dose (1 mg/kg/day) 3

Adjunctive Therapies

Plasma exchange should be considered for:

• Serum creatinine >300 µmol/L (>5.7 mg/dL) due to rapidly progressive glomerulonephritis 1
• Diffuse alveolar hemorrhage with hypoxemia (though evidence is weaker) 1

Avacopan (C5a receptor antagonist):

• May be considered in combination with rituximab or cyclophosphamide as a glucocorticoid-sparing strategy 1, 3
• Particularly useful in patients at high risk for glucocorticoid toxicity 3

Remission Induction for Non-Organ-Threatening Disease (GPA/MPA)

Treat with glucocorticoids combined with rituximab as first-line therapy. 1

Alternative agents (if rituximab unavailable):

• Methotrexate: Can be used but carries higher relapse risk requiring rigorous monitoring 1, 5
• Mycophenolate mofetil: 2000 mg/day in divided doses, particularly effective in MPO-ANCA positive patients 1, 3

Treatment of Eosinophilic Granulomatosis with Polyangiitis (EGPA)

For organ-threatening EGPA:

• High-dose glucocorticoids combined with cyclophosphamide 1
• Rituximab may be considered as an alternative 1

For non-organ-threatening EGPA:

• Glucocorticoids alone as initial therapy 1

For relapsing/refractory EGPA without organ-threatening disease:

• Mepolizumab is recommended 1

Maintenance Therapy

After achieving remission, continue maintenance therapy with rituximab for 24-48 months. 1

Rituximab maintenance dosing:

• 500 mg IV every 6 months (preferred based on recent evidence) 6
• Alternative: 1000 mg IV every 6 months 1

Alternative maintenance agents (if rituximab unavailable):

• Azathioprine: 1.5-2 mg/kg/day 1
• Methotrexate: Acceptable but higher relapse risk 1
• Mycophenolate mofetil: 2000 mg/day in divided doses 1

Duration considerations:

• Minimum 24 months for new-onset disease 1
• Longer duration (up to 48 months) for relapsing patients or those with increased relapse risk 1

Treatment of Relapse

For major relapse (organ-threatening):

• Rituximab is strongly preferred over cyclophosphamide based on superior response rates in relapsing disease 1, 6
• Reintroduce or intensify glucocorticoids combined with rituximab 375 mg/m² weekly for 4 weeks 1, 6

For minor relapse (non-organ-threatening):

• Increase glucocorticoid dose temporarily 6
• Consider adding or switching immunosuppressant if glucocorticoids alone insufficient 6

Combination Therapy for Severe Disease

For patients with severe renal involvement or diffuse alveolar hemorrhage, consider combination rituximab plus limited cyclophosphamide:

• Rituximab 375 mg/m² weekly for 4 weeks PLUS
• Cyclophosphamide 15 mg/kg IV at weeks 0 and 2 only 3, 7
• This regimen achieved 84% complete remission by 5 months with rapid glucocorticoid tapering 7

Monitoring and Disease Assessment

Base treatment decisions on structured clinical assessment rather than ANCA titers or B-cell levels alone. 1

• Monitor renal function, urinalysis with proteinuria quantification, and inflammatory markers regularly 4
• Test serum immunoglobulin levels before each rituximab course and in patients with recurrent infections 1
• Assess cardiovascular risk periodically, as mortality remains 2.6-fold higher than general population 4
• Investigate persistent unexplained hematuria in patients with prior cyclophosphamide exposure (bladder cancer risk) 1

Refractory Disease Management

For patients not responding to initial therapy:

• Perform thorough reassessment to exclude infection, malignancy, or alternative diagnoses 1
• Switch from cyclophosphamide to rituximab or vice versa 1
• Refer to or manage in close conjunction with a vasculitis expert center 1

Critical Safety Considerations

Infection prophylaxis is mandatory:

• Pneumocystis jirovecii prophylaxis with trimethoprim/sulfamethoxazole for all patients receiving cyclophosphamide 1, 4
• Alternative prophylaxis: dapsone or atovaquone if trimethoprim/sulfamethoxazole contraindicated 1

Common pitfalls to avoid:

• Do not delay treatment while awaiting biopsy in rapidly deteriorating patients 4
• Do not use ANCA titers alone to guide treatment changes; clinical assessment is paramount 1
• Do not discontinue maintenance therapy prematurely (minimum 24 months) 1
• Do not forget MESNA with cyclophosphamide to prevent hemorrhagic cystitis 1, 3