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

Initial Treatment for ANCA Vasculitis

For organ-threatening ANCA vasculitis, initiate remission induction with either rituximab (375 mg/m² weekly for 4 weeks) or cyclophosphamide (oral 2 mg/kg/day or IV 15 mg/kg at weeks 0,2,4,7,10,13) combined with glucocorticoids, with rituximab being preferred for relapsing disease. 1

Disease Severity Stratification

The treatment approach must be stratified based on disease severity and organ involvement:

Organ-Threatening Disease (Severe)

• Defined by: Renal involvement with creatinine >3.4 mg/dL, dialysis requirement, rapidly progressive glomerulonephritis, diffuse alveolar hemorrhage with hypoxemia, or other vital organ failure 1
• First-line induction therapy options:
  • Rituximab: 375 mg/m² weekly for 4 weeks 1
  • Cyclophosphamide: Either oral 2 mg/kg/day for 3-6 months OR IV 15 mg/kg at weeks 0,2,4,7,10,13 1
  • Combination approach: Rituximab 375 mg/m² weekly for 4 weeks with IV cyclophosphamide 15 mg/kg at weeks 0 and 2 1, 2

Non-Organ-Threatening Disease (Limited)

• First-line therapy: Glucocorticoids combined with methotrexate (15-25 mg/week) or mycophenolate mofetil (2000 mg/day in divided doses) 1, 3
• Reserve rituximab and cyclophosphamide for severe or refractory cases 3

Glucocorticoid Regimen

All patients require high-dose glucocorticoids initially with structured tapering 1:

• Initial dosing: 1 mg/kg/day prednisone (maximum 80 mg/day) or IV methylprednisolone 1000 mg daily for 1-3 days 1, 4
• Target by 3 months: 7.5-10 mg/day prednisone 1
• Structured taper: Follow protocol to reach 5-7.5 mg/day by 6 months 1

Avacopan as Glucocorticoid Alternative

• Avacopan 30 mg twice daily may be used as an alternative to glucocorticoids in combination with rituximab or cyclophosphamide 1, 5
• Preferred for: Patients at high risk of glucocorticoid toxicity or those with lower GFR who may benefit from greater renal recovery 1
• Evidence: Superior to prednisone for sustained remission at 52 weeks (65.7% vs 54.9%) 5

Dose Adjustments for Special Populations

Age-Based Cyclophosphamide Reduction 1

• Age >60 years: Reduce oral to 1.5 mg/kg/day; reduce IV to 12.5 mg/kg
• Age >70 years: Reduce oral to 1.0 mg/kg/day; reduce IV to 10 mg/kg

Renal Impairment 1

• GFR <30 mL/min/1.73m²: Reduce oral cyclophosphamide by 0.5 mg/kg/day; reduce IV by 2.5 mg/kg

Adjunctive Therapies

Plasma Exchange 1

• Consider for: Serum creatinine >3.4 mg/dL (>300 μmol/L), dialysis requirement, rapidly increasing creatinine, or diffuse alveolar hemorrhage with hypoxemia 1

Infection Prophylaxis 1, 3

• Mandatory: Trimethoprim/sulfamethoxazole (800/160 mg alternate days or 400/80 mg daily) for all patients receiving cyclophosphamide 1
• Alternatives if contraindicated: Dapsone or atovaquone 1

Cyclophosphamide-Specific Precautions 1, 3

• MESNA administration: Oral or IV to prevent hemorrhagic cystitis 1
• High fluid intake: Encourage on infusion days to dilute toxic metabolites 1

Rituximab vs Cyclophosphamide: Evidence-Based Selection

Rituximab Preferred When 4, 5:

• Relapsing disease: 67% remission rate vs 42% with cyclophosphamide 4
• Fertility preservation desired: No documented impact on reproductive potential 1
• Glucocorticoid toxicity risk: Allows for more rapid steroid taper 5

Equivalent Efficacy 4:

• New-onset disease: Both achieve ~64% remission at 6 months 4
• Major renal disease or alveolar hemorrhage: No significant difference in outcomes 4

Monitoring Requirements

During Induction 1, 3

• Weekly: Complete blood count
• Regular: Renal function and urinalysis
• Dose modification: For leukopenia <4000/μL or progressive decline 1

Transition to Maintenance Therapy

After achieving remission (typically 3-6 months) 1:

• Rituximab maintenance: 500 mg × 2 at remission, then 500 mg at months 6,12,18 (MAINRITSAN scheme) 1
• Azathioprine maintenance: 1.5-2 mg/kg/day with low-dose glucocorticoids (5-7.5 mg/day) 1
• Duration: 18 months to 4 years after induction 1

Common Pitfalls to Avoid

• Inadequate glucocorticoid tapering: Maintain structured taper to avoid both under-treatment and excessive toxicity 1
• Omitting infection prophylaxis: Pneumocystis prophylaxis is mandatory with cyclophosphamide 1, 3
• Premature discontinuation: Maintenance therapy for minimum 18 months required to prevent relapse 1
• Ignoring age/renal adjustments: Failure to reduce cyclophosphamide doses increases toxicity risk 1