What is the recommended management of vasculitis?

Management of Vasculitis

For ANCA-associated vasculitis (AAV), initiate remission induction with rituximab or cyclophosphamide combined with glucocorticoids, followed by rituximab maintenance therapy for at least 18-24 months. 1, 2

Remission Induction for GPA/MPA

Severe/Organ-Threatening Disease

• Use rituximab (375 mg/m² weekly × 4 weeks OR 1000 mg on days 1 and 15) or cyclophosphamide (oral 2 mg/kg/day or IV 15 mg/kg every 2-3 weeks) combined with glucocorticoids 1, 2
• Rituximab is preferred for relapsing disease, PR3-ANCA positive patients, and women of childbearing age 3
• Add avacopan (30 mg twice daily) as a glucocorticoid-sparing agent when there is high risk of glucocorticoid-related adverse events 4, 5

Glucocorticoid Dosing

• Start with pulse IV methylprednisolone (500-1000 mg daily × 3 days) or high-dose oral prednisone (1 mg/kg/day, max 60-80 mg) 1, 2
• Rapidly taper to 15 mg/day by week 6 and 5 mg/day by week 12-14 1, 5
• With avacopan, glucocorticoids can be discontinued by week 4 4

Plasma Exchange

• Consider plasma exchange for severe renal impairment (creatinine >300 μmol/L or dialysis-dependent) or diffuse alveolar hemorrhage 3, 5
• Recent evidence shows plasma exchange is not routinely indicated for all severe disease 3

Remission Maintenance

Rituximab is first-line maintenance therapy, superior to conventional immunosuppressants 1, 3

Rituximab Maintenance Protocol

• 500 mg IV every 6 months for 18 months minimum (total 4 infusions) 3
• Re-evaluate at 18 months: consider 4 additional biannual infusions (total 24 months) balancing relapse risk versus infection risk 3
• Monitor serum immunoglobulin levels before each rituximab course to detect secondary immunodeficiency 1

Alternative Maintenance Options

• Second-line: Azathioprine (2 mg/kg/day) or methotrexate (20-25 mg weekly) 1, 4
• Third-line: Mycophenolate mofetil (2000 mg/day) 4
• Continue low-dose glucocorticoids (5-7.5 mg/day prednisone) with non-rituximab regimens 1

EGPA-Specific Management

Severe EGPA

• Use cyclophosphamide or rituximab (NOT mepolizumab) for severe/organ-threatening disease 2
• Mepolizumab efficacy is unproven in severe active vasculitis 2

Non-Severe EGPA

• Mepolizumab (300 mg SC monthly) plus glucocorticoids is preferred over methotrexate/azathioprine/mycophenolate 2
• Mepolizumab demonstrates significant glucocorticoid-sparing effects 3

EGPA Maintenance

• For relapsing EGPA after remission induction, use mepolizumab 1
• Rituximab, methotrexate, or azathioprine are alternatives 1
• Benralizumab (IL-5 receptor antagonist) is noninferior to mepolizumab 3

Infection Prophylaxis

Mandatory prophylaxis for patients receiving rituximab, cyclophosphamide, or high-dose glucocorticoids: 1

• Trimethoprim-sulfamethoxazole (160/800 mg three times weekly) for Pneumocystis jirovecii pneumonia 1, 5
• Ensure vaccination schedules are current, ideally before starting immunosuppression 5

Monitoring Strategy

Base treatment decisions on structured clinical assessment, not ANCA or CD19+ B cell levels alone 1

Essential Monitoring

• Urinalysis at every visit for cyclophosphamide-treated patients (bladder cancer risk) 1
• Kidney function, proteinuria, and ANCA levels at baseline and follow-up 5
• Screen for cardiovascular risk factors, osteoporosis, and chronic kidney disease 1
• Immunoglobulin levels before each rituximab infusion 1

Relapse Management

Severe Relapse

• Re-induce with rituximab or cyclophosphamide plus glucocorticoids 2, 5
• Rituximab is preferred for relapsing disease 5

Non-Severe Relapse

• If on methotrexate/azathioprine: switch to rituximab 2
• For EGPA: use rituximab or mepolizumab depending on disease features 2

Refractory Disease

Switch treatment modalities if no response to initial induction therapy 5

• If cyclophosphamide fails: switch to rituximab
• If rituximab fails: consider cyclophosphamide or plasma exchange 5

Critical Caveats

• AAV requires multidisciplinary management by centers with vasculitis expertise due to disease rarity and complexity 1
• Rituximab significantly impacts humoral immunity and vaccine responses—plan vaccinations strategically 4
• Infection risk remains the primary concern throughout treatment—balance effective immunosuppression against comorbidities and frailty 4
• For kidney transplant candidates: AAV in remission with stage 5 CKD should be evaluated for transplantation; outcomes are similar to other causes 2