What is the initial treatment approach for patients with vasculitis?

Initial Treatment Approach for Vasculitis

For ANCA-associated vasculitis (AAV), initiate combination therapy with glucocorticoids plus either rituximab or cyclophosphamide immediately, without waiting for biopsy results in rapidly deteriorating patients. 1

Immediate Treatment Decisions for ANCA-Associated Vasculitis

When to Start Treatment Before Biopsy

• Begin immunosuppressive therapy immediately if clinical presentation is compatible with small-vessel vasculitis AND MPO- or PR3-ANCA serology is positive, especially in rapidly deteriorating patients 1
• Do not delay treatment waiting for kidney biopsy to be performed or reported 1
• Low suspicion for secondary vasculitis is required to proceed without biopsy 1

First-Line Induction Regimen

Glucocorticoids combined with rituximab OR cyclophosphamide is the recommended initial treatment for new-onset AAV 1, 2

Choosing Between Rituximab and Cyclophosphamide

Cyclophosphamide is preferred when: 1, 2

• Severe glomerulonephritis with serum creatinine >4 mg/dl (>354 μmol/l) 1
• Markedly reduced or rapidly declining GFR 1
• Consider combining 2 intravenous pulses of cyclophosphamide WITH rituximab in this severe setting 1

Rituximab is preferred when: 2

• Younger patients concerned about fertility 2
• Relapsing disease 2
• PR3-ANCA positive patients (higher relapse risk) 2

Glucocorticoid Dosing for AAV

• Initial dose: 1 mg/kg/day (maximum 60 mg/day) 2, 3
• Pulse intravenous methylprednisolone 1,000 mg daily for 1-3 days may be given prior to initial infusion 4
• Oral prednisone follows at 1 mg/kg/day (not exceeding 80 mg/day) with pre-specified tapering 4

Cyclophosphamide Administration Routes

Intravenous cyclophosphamide preferred for: 1

• Patients who already have moderate cumulative cyclophosphamide dose 1
• Lower white blood cell counts 1
• Ready access to infusion center 1
• Concerns about adherence to oral regimen 1

Oral cyclophosphamide preferred for: 1

• Cost is an important factor 1
• No easy access to infusion center 1
• Self-administered oral regimen is preferable 1
• Dose: 2 mg/kg/day for 3-6 months 4

Large Vessel Vasculitis (Giant Cell Arteritis, Takayasu Arteritis)

Immediate Glucocorticoid Therapy

Initiate high-dose glucocorticoids immediately for induction of remission in large vessel vasculitis 2, 3

• Dose: 40-60 mg/day prednisone-equivalent or 1 mg/kg/day (maximum 60 mg/day) 2, 3
• Maintain high-dose for one month before gradual tapering 2

Giant Cell Arteritis Specific Considerations

• Immediate initiation of high-dose glucocorticoids reduces recurrent stroke risk 2
• Consider adjunctive tocilizumab as steroid-sparing agent 2, 3
• Methotrexate is an alternative steroid-sparing option 2

Takayasu Arteritis Specific Approach

All patients should receive non-biological glucocorticoid-sparing agents in combination with glucocorticoids from the outset 2, 3

Critical Management Principles

Treatment Setting

Patients with AAV must be treated at centers with experience in AAV management 1, 2

Required capabilities include: 1

• Rapid serologic and histologic testing 1
• Availability of rituximab and plasma exchange 1
• Experience with treatment modalities and their complications 1
• Access to intensive care unit and acute hemodialysis 1

Supportive Prophylaxis

• Pneumocystis jiroveci prophylaxis for patients on immunosuppressive therapy 2
• Osteoporosis prophylaxis for patients on glucocorticoids 2

Monitoring for Relapse

ANCA persistence, increase in ANCA levels, or change from negative to positive predicts future relapse and should guide treatment decisions 1, 3

Common Pitfalls to Avoid

• Never delay treatment while waiting for biopsy results in rapidly deteriorating patients with positive ANCA serology 2
• Avoid alternate-day glucocorticoid therapy, which increases relapse risk 2
• Do not provide inadequate initial immunosuppression in severe disease 2
• Routine antiplatelet or anticoagulant therapy is not recommended for large vessel vasculitis unless indicated for other reasons 3
• Exclude vasculitis mimics such as thrombotic disorders (anti-phospholipid antibody syndrome) before initiating immunosuppression 5

Disease Activity Assessment

Monitor treatment response using Birmingham Vasculitis Activity Score (BVAS), with remission defined as BVAS = 0 1, 2, 3