What is the recommended treatment for a patient diagnosed with vasculitis?

Treatment of Vasculitis

For patients diagnosed with vasculitis, immediate high-dose glucocorticoid therapy combined with either rituximab or cyclophosphamide is recommended, with the specific regimen determined by vasculitis type, disease severity, and organ involvement. 1, 2

Initial Classification and Assessment

Before initiating treatment, vasculitis must be classified by:

• Vessel size involvement (large, medium, or small vessel) to guide appropriate management 3, 2
• Disease severity: Severe disease includes life- or organ-threatening manifestations such as alveolar hemorrhage, glomerulonephritis, central nervous system vasculitis, mononeuritis multiplex, cardiac involvement, mesenteric ischemia, or limb/digit ischemia 1
• Vasculitis subtype: ANCA-associated vasculitis (GPA, MPA, EGPA), large vessel vasculitis (Giant Cell Arteritis, Takayasu Arteritis), or other forms 1, 2

Critical pitfall: In ANCA-associated vasculitis with positive serology and rapidly deteriorating patients, treatment should not be delayed while waiting for biopsy results 2

Treatment by Vasculitis Type and Severity

ANCA-Associated Vasculitis (GPA/MPA/EGPA)

Severe/Organ-Threatening Disease

Remission induction requires combination therapy with:

• Glucocorticoids: Either IV pulse methylprednisolone 500-1,000 mg/day for 3-5 days OR high-dose oral prednisone 1 mg/kg/day (maximum 80 mg/day) 1
• PLUS either:
  • Rituximab 375 mg/m² IV weekly for 4 weeks OR 1,000 mg IV on days 1 and 15 1, 4
  • OR Cyclophosphamide up to 2 mg/kg/day oral for 3-6 months OR 15 mg/kg IV every 2 weeks for 3 doses, then every 3 weeks 1, 2

The 2021 ACR/Vasculitis Foundation guideline demonstrates non-inferiority between rituximab and cyclophosphamide, with 64% achieving complete remission with rituximab versus 53% with cyclophosphamide at 6 months. 1, 4

Choosing between rituximab and cyclophosphamide:

• Favor rituximab for: Younger patients concerned about fertility, relapsing disease, patients with hepatic dysfunction 1, 2
• Favor cyclophosphamide for: Severe renal disease with markedly reduced or rapidly declining renal function 2
• Consider combination rituximab + cyclophosphamide for: Severe disease with pulmonary hemorrhage or rapidly progressive renal disease 2

Adjunctive therapy considerations:

• Plasma exchange: May be considered for patients with dialysis requirement, rapidly progressive renal failure, or diffuse alveolar hemorrhage with hypoxemia, though recent evidence shows increased infection risk 1, 2
• Reduced-dose glucocorticoid regimen is conditionally recommended over standard-dose, as it provides similar efficacy with decreased infection risk 1

Nonsevere Disease (GPA without life/organ-threatening manifestations)

• Methotrexate up to 25 mg/week (subcutaneous or oral) PLUS glucocorticoids is preferred over cyclophosphamide or rituximab 1
• Methotrexate is favored due to lower toxicity profile, though rituximab may be preferred in specific situations including recurrent relapses on methotrexate or concerns about compliance 1

Large Vessel Vasculitis

Giant Cell Arteritis

• Immediate high-dose glucocorticoids 40-60 mg/day prednisone-equivalent to reduce recurrent stroke risk 3, 2
• Maintain high-dose for one month before gradual tapering 2
• Consider adjunctive tocilizumab as steroid-sparing agent 3, 2
• Alternative steroid-sparing agents include methotrexate 2

Takayasu Arteritis

• All patients should receive non-biological glucocorticoid-sparing agents in combination with glucocorticoids 3, 2
• Initial glucocorticoid dose: 1 mg/kg/day (maximum 60 mg/day) 3, 2

Remission Maintenance Therapy

After achieving remission with cyclophosphamide or rituximab for severe GPA/MPA, rituximab is conditionally recommended over methotrexate or azathioprine for maintenance. 1

Evidence-based maintenance options include:

• Rituximab 500 mg IV every 6 months OR 1,000 mg IV every 4 months (adults); 250 mg/m² IV every 6 months (children) 1, 2
  • Associated with lower relapse rate than azathioprine (67% vs 42% remission rate) 2
• Azathioprine up to 2 mg/kg/day 1, 2
• Methotrexate up to 25 mg/week (contraindicated if GFR <60 mL/min per 1.73 m²) 1, 2
• Mycophenolate mofetil up to 1,500 mg oral twice daily 1, 2

Glucocorticoid maintenance: Continue at 5-7.5 mg/day for 2 years, then reduce by 1 mg every 2 months, with goal of tapering to ≤10 mg/day during remission 1, 2

Duration: Minimum 18-24 months for initial remission; extended therapy to 4 years after diagnosis reduces relapse risk 2

EGPA-Specific Considerations

• Mepolizumab 300 mg subcutaneous every 4 weeks can be used for both induction and maintenance in EGPA 1

Glucocorticoid Tapering Strategy

Critical pitfall: Avoid alternate-day glucocorticoid therapy, which increases relapse risk 2

The glucocorticoid dose should be tapered to ≤10 mg/day prednisolone during remission, then reduced gradually after 6-18 months depending on patient response, with aim of discontinuing therapy 1

Refractory Disease Management

For patients with progressive disease despite optimal therapy, alternative options include:

• Intravenous immunoglobulin 2 g/kg over 5 days (check serum immunoglobulin levels first; contraindicated in IgA deficiency) 1
• Mycophenolate mofetil 2 g/day 1
• Rituximab for refractory ANCA-associated vasculitis (91% remission rate in open-label trials) 1, 5
• Infliximab 3-5 mg/kg/infusion every 1-2 months 1

Patients with refractory disease should be referred to expert centers for enrollment in clinical trials. 1, 2

Monitoring and Follow-up

• Disease activity assessment using Birmingham Vasculitis Activity Score (BVAS) 3, 2
• ANCA levels: Persistence, increase, or change from negative to positive may predict future relapse and should inform treatment decisions 3, 2
• Monitor for drug toxicity: Acute fall in white cell count, progressive leukopenia, renal function 2
• Infection surveillance: Highest risk with combination immunosuppression 4

Supportive Care

• Prophylaxis against Pneumocystis jiroveci for patients on immunosuppressive therapy 2
• Osteoporosis prophylaxis for patients on long-term glucocorticoids 2
• Antiemetic therapy routinely with IV cyclophosphamide 1
• Hydration (oral or IV fluids) on day of cyclophosphamide infusion to prevent hemorrhagic cystitis 1
• Trimethoprim/sulfamethoxazole 160 mg twice daily may reduce relapse risk in GPA when added to standard maintenance 1

Common Pitfalls to Avoid

• Delaying treatment while awaiting biopsy in rapidly deteriorating patients 2
• Using glucocorticoid monotherapy for severe disease 1
• Inadequate initial immunosuppression in severe disease 2
• Routine use of antiplatelet or anticoagulant therapy (not recommended unless indicated for other reasons) 3
• Using methotrexate in patients with GFR <60 mL/min per 1.73 m² 2