What is the recommended initial treatment for ANCA (Antineutrophil Cytoplasmic Antibody)-associated vasculitis according to the KDIGO (Kidney Disease: Improving Global Outcomes) guideline?

Initial Treatment for ANCA-Associated Vasculitis According to KDIGO Guidelines

According to the 2024 KDIGO clinical practice guideline, glucocorticoids in combination with either rituximab or cyclophosphamide are recommended as the initial treatment for new-onset ANCA-associated vasculitis (AAV). 1

Treatment Algorithm

First-Line Induction Therapy

• Standard approach: Glucocorticoids + either rituximab or cyclophosphamide 1
• Initial glucocorticoid dosing:
  • IV methylprednisolone 500-1000 mg/day for 1-3 days (in severe cases)
  • Followed by oral prednisone 1 mg/kg/day (maximum 60-80 mg/day) 2
  • Rapid tapering schedule following PEXIVAS scheme is recommended to minimize adverse effects 2

Choosing Between Rituximab and Cyclophosphamide

The choice between rituximab and cyclophosphamide depends on several factors:

Cyclophosphamide is preferred when:

• Severe glomerulonephritis (serum creatinine >4 mg/dl [354 μmol/l]) 1
• Rapidly declining renal function 1, 2

Rituximab is preferred when:

• Less severe renal impairment 2
• Relapsing disease 3, 4
• Fertility preservation is important 2

Combination therapy consideration:

• For extremely severe, rapidly progressive disease, a combination of rituximab with 2 intravenous pulses of cyclophosphamide can be considered 1, 2

Cyclophosphamide Administration Routes

Intravenous cyclophosphamide is preferred for:

• Patients who already have moderate cumulative cyclophosphamide exposure
• Patients with lower white blood cell counts
• Patients with ready access to infusion centers
• Patients with potential adherence issues to oral regimens 1

Oral cyclophosphamide is preferred for:

• Cost-conscious situations
• Limited access to infusion centers
• Patients who prefer self-administered oral regimens 1

Dosing Regimens

Cyclophosphamide:

• Oral: 2 mg/kg/day for 3-6 months depending on disease activity
• Intravenous: 15 mg/kg at weeks 0,2,4,7,10,13 (and weeks 16,19,21,24 if necessary) 2

Rituximab:

• 375 mg/m² weekly for 4 weeks, or
• 1 g at weeks 0 and 2 2

Important Clinical Considerations

Timing of Treatment

• Do not delay immunosuppressive therapy in patients with clinical presentation compatible with small-vessel vasculitis and positive MPO or PR3-ANCA serology, especially in rapidly deteriorating patients 1
• Treatment can be initiated before kidney biopsy results are available in appropriate clinical scenarios 1

Reduced-Dose Glucocorticoid Approach

• Recent evidence supports using reduced-dose glucocorticoids (0.5 mg/kg/day) with rituximab for non-severe AAV, which is noninferior to high-dose regimens (1 mg/kg/day) while causing fewer serious adverse events and infections 5

Monitoring During Treatment

• Regular monitoring of kidney function, proteinuria, and ANCA levels 2, 6
• ANCA persistence, increase in levels, or change from negative to positive may predict future relapse and should inform treatment decisions 1, 6

Treatment Setting

• Patients with AAV should be treated at centers with experience in AAV management 1

Prophylaxis During Treatment

• Pneumocystis jirovecii prophylaxis with trimethoprim/sulfamethoxazole for patients on cyclophosphamide
• Bone protection for patients on long-term glucocorticoids 2

By following this evidence-based approach to initial treatment of ANCA-associated vasculitis, clinicians can optimize outcomes while minimizing treatment-related complications.