What is the recommended treatment approach for a 57‑year‑old woman with myeloperoxidase anti‑neutrophil cytoplasmic antibody‑positive systemic vasculitis?

Treatment Approach for MPO-ANCA Positive Vasculitis in a 57-Year-Old Female

For this 57-year-old woman with MPO-ANCA positive vasculitis, initiate remission induction with rituximab plus reduced-dose glucocorticoids, as this combination achieves equivalent remission rates to cyclophosphamide while allowing faster steroid tapering and lower infection risk. 1

Initial Assessment and Treatment Timing

• Begin immunosuppressive therapy immediately without waiting for kidney biopsy if the clinical presentation is compatible with ANCA-associated vasculitis (AAV) and MPO-ANCA serology is positive. 2, 3 This is particularly critical if renal function is rapidly deteriorating. 3

• Assess disease severity by measuring serum creatinine, eGFR, urinalysis for hematuria/proteinuria, and evaluate for extrarenal manifestations (pulmonary hemorrhage, skin lesions, neuropathy, upper respiratory tract involvement). 1

Remission Induction Regimen

Primary Immunosuppression

Rituximab is the preferred induction agent for MPO-ANCA vasculitis because:

• MPO-ANCA patients have lower relapse risk than PR3-ANCA patients, making rituximab equally effective to cyclophosphamide 1
• Rituximab allows for lower cumulative glucocorticoid exposure 1
• At 57 years old, avoiding cyclophosphamide reduces age-related toxicity concerns 1

Rituximab dosing: 1, 3

• 375 mg/m² IV weekly for 4 weeks (standard protocol), OR
• 1000 mg IV on days 0 and 14 (alternative protocol)

Glucocorticoid Regimen

Use the reduced-dose PEXIVAS protocol (proven noninferior to high-dose with fewer infections): 1

• Week 1: 50-75 mg daily (weight-adjusted: 50 mg if <50 kg, 60 mg if 50-75 kg, 75 mg if >75 kg)
• Week 2: 25-40 mg daily (weight-adjusted)
• Weeks 3-4: 20-30 mg daily
• Weeks 5-6: 15-25 mg daily
• Taper to 5 mg daily by weeks 19-20
• Maintain 5 mg daily through week 52

This rapid taper is as effective as standard dosing but significantly safer, particularly for patients with GFR <50 ml/min per 1.73 m². 1

Alternative Consideration: Avacopan

Avacopan (30 mg PO twice daily) can replace glucocorticoids entirely if this patient has high risk for steroid toxicity (diabetes, osteoporosis, obesity, psychiatric history). 1 The ADVOCATE trial demonstrated noninferiority to prednisone with potential for better kidney function recovery, especially if eGFR <20 ml/min per 1.73 m². 1

When to Consider Cyclophosphamide Instead

Switch to cyclophosphamide if: 1, 3

• Serum creatinine >4 mg/dL (>354 µmol/L)
• Patient requires dialysis
• Rapidly progressive glomerulonephritis with doubling creatinine
• Severe diffuse alveolar hemorrhage requiring mechanical ventilation

Cyclophosphamide dosing (if needed): 1

• IV: 15 mg/kg at weeks 0,2,4,7,10,13
• Reduce to 12.5 mg/kg if age >60 years (applicable to this 57-year-old if she turns 60 during treatment)
• Reduce by 2.5 mg/kg if GFR <30 ml/min per 1.73 m²

Plasma Exchange Decision

Do NOT use plasma exchange unless: 1, 3

• Serum creatinine >3.4 mg/dL (>300 µmol/L)
• Patient requires dialysis
• Diffuse alveolar hemorrhage with hypoxemia

The PEXIVAS trial showed no mortality or ESRD benefit from routine plasma exchange, so reserve it only for the most severe presentations. 1

Mandatory Supportive Care

Pneumocystis jirovecii prophylaxis is non-negotiable: 3, 4

• Trimethoprim-sulfamethoxazole 800/160 mg three times weekly OR
• 400/80 mg daily (alternative dosing)
• Continue throughout induction and maintenance therapy

Monitoring During Induction (First 6 Months)

• Renal function: Serum creatinine and eGFR every 2-4 weeks 2
• Urinalysis: Monitor for hematuria and proteinuria resolution 2
• Complete blood count: Weekly initially, then every 2-4 weeks to detect cytopenias 2, 4
• MPO-ANCA titers: Repeat at 3 and 6 months (rising titers predict relapse) 2
• Infection surveillance: This is the most common serious adverse event (25-28 per 100 patient-years) 4

Transition to Maintenance Therapy

After achieving remission (typically 3-6 months, defined as BVAS = 0): 1

Preferred maintenance option: Rituximab 1

• MAINRITSAN scheme: 500 mg IV × 2 doses at remission, then 500 mg at months 6,12, and 18
• RITAZAREM scheme: 1000 mg IV after induction, then at months 4,8,12, and 16

Alternative maintenance options (if rituximab unavailable/contraindicated): 1

• Azathioprine 1.5-2 mg/kg/day for 18-24 months, then reduce to 1 mg/kg/day until 4 years
• Mycophenolate mofetil 2000 mg/day (divided doses) for 2 years
• Continue low-dose prednisone 5-7.5 mg/day for 2 years, then taper by 1 mg every 2 months

Maintenance duration: 18 months to 4 years minimum 1

Critical Pitfalls to Avoid

• Never delay treatment waiting for biopsy in a patient with compatible clinical presentation and positive MPO-ANCA 2, 3
• Do not use methotrexate if GFR <60 ml/min per 1.73 m² (nephrotoxic) 1
• Avoid premature discontinuation of maintenance therapy (minimum 18 months required) 1
• Do not use mycophenolate mofetil for induction if rapidly progressive kidney disease is present (higher relapse risk than cyclophosphamide/rituximab) 1
• Monitor for hypogammaglobulinemia with rituximab (27% develop low IgA, 58% low IgG by 6 months) 4

MPO-ANCA Specific Considerations

MPO-ANCA patients have distinct characteristics: 1, 5

• Lower relapse risk compared to PR3-ANCA (particularly important for maintenance planning)
• Better response to mycophenolate mofetil than PR3-ANCA patients (though still inferior to rituximab/cyclophosphamide for severe disease) 1
• May have better kidney function recovery with avacopan 1

This patient's age (57 years) and MPO-ANCA status make rituximab with reduced-dose glucocorticoids the optimal balance of efficacy and safety. 1, 3