What is the step for treating vasculitis?

Treatment Approach for Vasculitis

For ANCA-associated vasculitis (AAV), initiate remission induction with either rituximab or cyclophosphamide combined with glucocorticoids, followed by maintenance therapy with rituximab or azathioprine plus low-dose glucocorticoids for 18 months to 4 years. 1

Induction Therapy for ANCA-Associated Vasculitis

First-Line Induction Options

Rituximab-based induction:

• Rituximab 375 mg/m² weekly for 4 weeks, combined with glucocorticoids 1
• Alternative: Rituximab 375 mg/m² weekly × 4 weeks plus IV cyclophosphamide 15 mg/kg at weeks 0 and 2 1
• Premedicate with antihistamine and acetaminophen before each infusion 1

Cyclophosphamide-based induction:

• Oral: 2 mg/kg/day for 3 months, continue up to maximum 6 months if ongoing activity 1
  • Reduce to 1.5 mg/kg/day for age >60 years
  • Reduce to 1.0 mg/kg/day for age >70 years
  • Reduce by 0.5 mg/kg/day for GFR <30 ml/min/1.73 m² 1
• IV: 15 mg/kg at weeks 0,2,4,7,10,13 (extend to weeks 16,19,21,24 if required) 1
  • Reduce to 12.5 mg/kg for age >60 years
  • Reduce to 10 mg/kg for age >70 years
  • Reduce by 2.5 mg/kg for GFR <30 ml/min/1.73 m² 1

Mycophenolate mofetil (alternative for less severe disease):

• 2000 mg/day in divided doses, may increase to 3000 mg/day for poor treatment response 1

Glucocorticoid Dosing During Induction

• IV methylprednisolone 1000 mg daily for 1-3 days prior to initial infusion 1
• Followed by oral prednisone 1 mg/kg/day (maximum 80 mg/day) with pre-specified tapering 1, 2
• High-dose glucocorticoids (40-60 mg/day prednisone-equivalent) should be initiated immediately 2

Adjunctive Therapy for Severe Disease

Plasma exchange indications:

• Serum creatinine >3.4 mg/dl (>300 μmol/l) 1
• Patients requiring dialysis or rapidly increasing creatinine 1
• Diffuse alveolar hemorrhage with hypoxemia 1

Avacopan (alternative to glucocorticoids):

• 30 mg twice daily as alternative to glucocorticoids, combined with rituximab or cyclophosphamide induction 1
• Particularly beneficial for patients at increased risk of glucocorticoid toxicity 1
• Patients with lower GFR may benefit from greater GFR recovery 1

Maintenance Therapy After Remission Induction

Primary Maintenance Options

Rituximab (preferred for relapsing disease):

• MAINRITSAN scheme: 500 mg × 2 at complete remission, then 500 mg at months 6,12, and 18 1
• RITAZAREM scheme: 1000 mg infusion after induction, then at months 4,8,12, and 16 1

Azathioprine:

• Start at 1.5-2 mg/kg/day at complete remission 1
• Continue until 1 year after diagnosis, then decrease by 25 mg every 3 months 1
• Extend until 4 years after diagnosis: maintain 1.5-2 mg/kg/day for 18-24 months, then decrease to 1 mg/kg/day until 4 years, then taper by 25 mg every 3 months 1

Mycophenolate mofetil (alternative):

• 2000 mg/day in divided doses at complete remission for 2 years 1
• Extend until 4 years after diagnosis with same tapering schedule as azathioprine 1

Methotrexate (alternative):

• Only for patients with GFR ≥60 ml/min/1.73 m² 1
• Use as alternative for patients intolerant of azathioprine 1

Glucocorticoid Maintenance

• Continue at 5-7.5 mg/day for 2 years 1
• Then slowly reduce by 1 mg every 2 months 1

Duration of Maintenance Therapy

• Optimal duration: 18 months to 4 years after induction of remission 1
• Most patients should receive maintenance therapy even after rituximab induction 1

Management of Relapsing Disease

Reinduction protocol:

• Reinitiate induction therapy, preferably with rituximab 1
• Use same dosing as initial induction 1

Management of Refractory Disease

Treatment escalation options:

• Increase glucocorticoids (IV or oral) 1
• Add rituximab if cyclophosphamide was used previously, or vice versa 1
• Consider plasma exchange 1

Treatment for Large Vessel Vasculitis

Giant Cell Arteritis:

• High-dose glucocorticoids: 1 mg/kg/day (maximum 60 mg/day) 2
• Consider adjunctive tocilizumab in selected patients 2

Takayasu Arteritis:

• All patients should receive non-biological glucocorticoid-sparing agents combined with glucocorticoids 2

Treatment for Cutaneous Vasculitis

Isolated Cutaneous Disease (Non-Severe)

Conservative management:

• Leg elevation, avoid standing, avoid cold temperatures and tight-fitting clothing 3, 4
• NSAIDs or aspirin 3
• Antihistamines 3

Mild recurrent/persistent disease:

• Colchicine (first-choice) 3, 4
• Dapsone (first-choice) 3, 4

Severe Cutaneous or Systemic Disease

Immediate immunosuppression:

• High-dose glucocorticoids (prednisone 1 mg/kg/day) combined with cyclophosphamide 5, 4
• Rituximab as alternative to cyclophosphamide (91% remission rate in refractory cases) 5

Maintenance after remission:

• Azathioprine 1-2 mg/kg/day 5
• Continue for at least 18 months in complete remission 5
• Maintain high-dose glucocorticoids for minimum 1 month before gradual taper 5

Refractory cutaneous disease:

• IVIG 2 g/kg over 5 days 5
• Mycophenolate mofetil 2 g/day 5
• Rituximab 375 mg/m² weekly for 4 weeks 5

Critical Supportive Care

Infection prophylaxis:

• Trimethoprim-sulfamethoxazole for all patients receiving cyclophosphamide 5

Bone protection:

• Calcium, vitamin D, and bisphosphonates for all patients on glucocorticoids 5

Important Caveats

• Drug-induced vasculitis often resolves with withdrawal of the offending agent alone, without need for immunosuppression 6
• Distinguish between isolated cutaneous vasculitis and systemic vasculitis with cutaneous manifestations, as treatment differs substantially 5
• Rituximab demonstrated non-inferiority to cyclophosphamide for complete remission at 6 months in AAV (64% vs 53%) 7
• Confirm diagnosis with imaging or histology before initiating treatment for large vessel vasculitis 2