What are the recommended medications for induction and maintenance therapy in antineutrophil cytoplasmic antibody‑associated vasculitis?

Medications for ANCA-Associated Vasculitis

Induction Therapy

For Organ-Threatening or Life-Threatening Disease (GPA/MPA)

Combine glucocorticoids with either rituximab or cyclophosphamide; rituximab is preferred for relapsing disease. 1

• Glucocorticoid dosing: Start with oral prednisolone 50-75 mg/day (based on body weight), taper stepwise to achieve 5 mg/day by 4-5 months 1
• Rituximab: 375 mg/m² IV weekly for 4 weeks 2, 3
• Cyclophosphamide: Either oral 2 mg/kg/day (max 200 mg) or IV pulses 0.6 g/m² monthly 4
• Rituximab superiority in relapsing disease: At 6 months, 64% of rituximab patients achieved complete remission versus 53% with cyclophosphamide-azathioprine, with sustained benefit through 18 months 3

For Non-Organ-Threatening Disease (GPA/MPA)

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

• Methotrexate or mycophenolate mofetil can serve as alternatives to rituximab when rituximab is unavailable or contraindicated 1, 5

Glucocorticoid-Sparing Strategy

Avacopan (60 mg twice daily) combined with rituximab or cyclophosphamide may be considered to substantially reduce glucocorticoid exposure. 1

• This option is particularly valuable for patients at high risk of glucocorticoid toxicity 1
• Post-hoc analysis suggests greater GFR recovery with avacopan in patients with GFR <30 ml/min per 1.73 m² 1

Adjunctive Therapy for Severe Renal Disease

Consider plasma exchange for patients with serum creatinine >300 µmol/L (>3.4 mg/dL) due to active glomerulonephritis, those requiring dialysis, or those with rapidly increasing creatinine. 1

• Do not routinely use plasma exchange for alveolar hemorrhage 1

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Maintenance Therapy

For GPA and MPA

Rituximab is recommended as first-line maintenance therapy after induction with either rituximab or cyclophosphamide. 1, 5

• Rituximab dosing: 500 mg IV every 6 months 1
• Duration: Continue for 24-48 months after achieving remission in new-onset disease 1
• Relapsing patients: Consider longer duration therapy, though this must be balanced against infection risk 1
• Superiority data: At 28 months, major relapses occurred in 17 azathioprine patients versus only 3 rituximab patients, with 8 renal relapses in the azathioprine group versus 0 in the rituximab group 1

Alternative Maintenance Agents

Azathioprine or methotrexate may be considered when rituximab is unavailable or contraindicated. 1, 5

• Azathioprine is preferred over mycophenolate mofetil: The IMPROVE trial showed 42 relapses with mycophenolate versus 30 with azathioprine (p<0.01) 1

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EGPA-Specific Recommendations

Organ-Threatening EGPA

Use high-dose glucocorticoids combined with cyclophosphamide. 1

• High-dose glucocorticoids plus rituximab may be considered as an alternative 1

Non-Organ-Threatening EGPA

Glucocorticoids alone are recommended for initial therapy. 1

Relapsing or Refractory EGPA (Without Organ-Threatening Disease)

Mepolizumab is recommended. 1

EGPA Maintenance

Consider methotrexate, azathioprine, mepolizumab, or rituximab after induction for organ-threatening disease. 1

• For relapsing EGPA after non-organ-threatening manifestations: Mepolizumab is specifically recommended 1

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Refractory Disease Management

For patients failing to respond after 4 weeks of standard induction therapy, switch from cyclophosphamide to rituximab or vice versa. 1, 4

• Before switching, reassess: confirm the diagnosis is truly AAV, verify optimal drug dosing has been achieved, distinguish active disease from damage, and exclude infection or malignancy 1
• All refractory patients should be managed in conjunction with or referred to a vasculitis expert center 1, 4

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Essential Supportive Care

Infection Prophylaxis

Provide trimethoprim-sulfamethoxazole (800/160 mg twice daily or alternate-day dosing) for all patients receiving rituximab, cyclophosphamide, or high-dose glucocorticoids to prevent Pneumocystis jirovecii pneumonia. 1, 4, 2

• Co-administer MESNA with cyclophosphamide to prevent hemorrhagic cystitis 4

Monitoring Strategy

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

• Measure serum immunoglobulin concentrations before each rituximab course to detect secondary immunodeficiency 1
• In the rituximab group of the GPA/MPA trial, 27%, 58%, and 51% of patients with normal baseline levels developed low IgA, IgG, and IgM, respectively, by 6 months 2

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Critical Pitfalls to Avoid

• Do not delay switching therapy in refractory disease: Lack of response after 4 weeks warrants immediate reassessment and treatment change 4
• Do not use ANCA titers to guide treatment changes: Clinical assessment is superior 1
• Do not stop maintenance therapy prematurely: Early cessation is associated with increased relapse risk 1
• Do not assume all patients tolerate standard glucocorticoid doses: Consider avacopan for those at high risk of glucocorticoid toxicity 1
• Do not use mycophenolate mofetil preferentially over azathioprine for maintenance: It has higher relapse rates 1