What are the treatments for Granulomatosis with Polyangiitis (GPA) and retinal vasculitis?

Treatment of Granulomatosis with Polyangiitis (GPA) and Retinal Vasculitis

For patients with Granulomatosis with Polyangiitis (GPA) and retinal vasculitis, the recommended treatment is a combination of high-dose glucocorticoids and rituximab as first-line therapy for remission induction, followed by rituximab for maintenance therapy. 1

Remission Induction Therapy

For Organ-Threatening or Life-Threatening Disease (including retinal vasculitis)

• First-line therapy:

  • Glucocorticoids: Start with oral prednisolone 50-75 mg/day (weight-dependent) 1
    • Consider IV pulse methylprednisolone 500-1000 mg daily for 3 days in severe cases
    • Follow stepwise reduction to reach 5 mg/day by 4-5 months 1
  • PLUS Rituximab: 375 mg/m² weekly for 4 weeks OR two 1000 mg infusions 2 weeks apart 1, 2

• Alternative option:

  • Cyclophosphamide: Can be used instead of rituximab, particularly in treatment-naïve patients 1
    • IV regimen: 15 mg/kg every 2-3 weeks (adjusted for renal function)
    • Oral regimen: 2 mg/kg/day (maximum 200 mg/day)

• Additional considerations:

  • Avacopan may be considered in combination with rituximab or cyclophosphamide to reduce glucocorticoid exposure 1
  • Plasma exchange may be considered for patients with serum creatinine >300 μmol/L due to active glomerulonephritis 1

For Retinal Vasculitis Specifically

Retinal vasculitis represents severe ocular involvement and should be treated as organ-threatening disease due to the risk of permanent vision loss 3, 4. Early aggressive therapy is crucial to preserve vision.

• Immediate ophthalmology consultation
• Consider local therapy in addition to systemic treatment:
  • Periocular or intravitreal corticosteroid injections may be needed in severe cases
  • Close monitoring of intraocular pressure

Maintenance Therapy

After achieving remission (typically 3-6 months):

• First-line maintenance: Rituximab 1

  • Dosing: 500 mg every 6 months OR 1000 mg every 4-6 months
  • Continue for at least 24-48 months after remission induction 1

• Alternative options (if rituximab is contraindicated or unavailable):

  • Azathioprine: 2 mg/kg/day
  • Methotrexate: 20-25 mg weekly
  • Mycophenolate mofetil: 2 g/day 1, 5

Treatment Monitoring

• Regular clinical assessment using Birmingham Vasculitis Activity Score (BVAS)

• Laboratory monitoring:

  • Complete blood count, renal function, liver function tests
  • Urinalysis
  • C-reactive protein and erythrocyte sedimentation rate
  • ANCA levels (though treatment decisions should not be based solely on ANCA titers) 1

• Ophthalmologic monitoring:

  • Regular fundoscopic examinations
  • Visual acuity testing
  • Fluorescein angiography to assess vasculitis activity 4

Management of Refractory Disease

For patients not responding to initial therapy:

1. Reassess diagnosis and ensure adequate drug exposure
2. Consider switching from cyclophosphamide to rituximab or vice versa 1
3. Consider referral to a specialized vasculitis center
4. Additional options for refractory disease:
   • Mycophenolate mofetil
   • IVIG
   • TNF inhibitors (limited evidence)

Important Considerations

• Early treatment is crucial: Retinal vasculitis can lead to permanent vision loss if not treated promptly
• Infection prophylaxis: Consider PCP prophylaxis with trimethoprim-sulfamethoxazole during induction therapy
• Bone health: Calcium and vitamin D supplementation, consider bisphosphonates for long-term steroid use
• Vaccination: Update vaccinations before starting immunosuppression when possible

Treatment Duration

• Maintenance therapy should continue for at least 24-48 months following induction of remission 1
• Longer duration may be needed for patients with relapsing disease
• Regular assessment of disease activity should guide treatment decisions rather than ANCA testing alone 1

The evidence strongly supports rituximab as the preferred agent for both induction and maintenance therapy in GPA with organ involvement, including retinal vasculitis, due to its efficacy and favorable safety profile compared to cyclophosphamide 1, 2, 5.