What is the treatment for Wegener's granulomatosis (Granulomatosis with Polyangiitis)?

Treatment of Wegener's Granulomatosis (Granulomatosis with Polyangiitis)

The standard treatment for Wegener's granulomatosis (now called Granulomatosis with Polyangiitis or GPA) consists of a combination of glucocorticoids with either cyclophosphamide or rituximab for remission induction, followed by maintenance therapy with less toxic agents. 1

Disease Classification and Initial Assessment

GPA is a systemic vasculitis characterized by:

• Necrotizing granulomatous inflammation of the upper and lower respiratory tract
• Glomerulonephritis
• Small-vessel vasculitis involving arteries and veins

Before initiating treatment, assess:

• Disease severity (organ-threatening vs. non-organ-threatening)
• Extent of organ involvement (especially renal, pulmonary, and neurological)
• Presence of life-threatening manifestations

Treatment Algorithm

1. Remission Induction for Severe/Organ-Threatening Disease

First-line therapy:

• Glucocorticoids (high-dose) plus either:
  • Rituximab (375 mg/m² weekly for 4 weeks or 1000 mg given twice, 2 weeks apart) 1, 2
  • Cyclophosphamide (oral or IV pulse) 1

Rituximab is preferred over cyclophosphamide in patients with childbearing potential or those with previous cyclophosphamide exposure 1

Glucocorticoid regimen:

• Initial: IV methylprednisolone pulses (500-1000 mg daily for 3 days) in severe cases
• Followed by oral prednisone 1 mg/kg/day (maximum 60-80 mg)
• Taper to 7.5-10 mg/day by 3-5 months 1
• Consider reduced-dose regimen to minimize toxicity 1

For patients with rapidly progressive glomerulonephritis or pulmonary hemorrhage:

• Consider plasma exchange in selected cases with high risk of progression to end-stage renal disease 1

2. Remission Induction for Non-Severe/Non-Organ-Threatening Disease

• Glucocorticoids plus either:
  • Methotrexate (preferred over cyclophosphamide) 1
  • Mycophenolate mofetil (alternative) 1

3. Remission Maintenance Therapy

After achieving remission (typically within 3-6 months), switch to maintenance therapy:

Preferred agents (in order of preference): 1

1. Rituximab (500 mg every 6 months)
2. Methotrexate or Azathioprine
3. Mycophenolate mofetil or Leflunomide

Duration of maintenance therapy:

• 24-48 months for new-onset disease
• Longer duration for relapsing disease 1
• Consider patient preferences and risks of continued immunosuppression

4. Treatment of Relapses

• For severe relapses: Treat as new-onset disease with glucocorticoids plus rituximab or cyclophosphamide 1
• For non-severe relapses: Consider increasing glucocorticoid dose and optimizing current immunosuppressive therapy

Special Considerations

Airway Stenosis

Subglottic or tracheobronchial stenosis (occurs in 5-23% of patients) may require:

• Bronchoscopic interventions
• Dilation procedures
• YAG laser treatment
• Airway stent placement 1

Infection Prevention

• Pneumocystis jirovecii prophylaxis with trimethoprim/sulfamethoxazole (800/160 mg on alternate days or 400/80 mg daily) for all patients on cyclophosphamide 1
• Regular monitoring for cytomegalovirus and hepatitis B reactivation in patients receiving rituximab 2

Monitoring During Treatment

• Complete blood counts with differential at regular intervals
• Renal function tests
• Urinalysis for hematuria/proteinuria
• ANCA titers (though treatment decisions should not be based solely on ANCA levels)
• Regular screening for glucocorticoid-related comorbidities

Treatment Outcomes

With appropriate therapy:

• Complete remission is achieved in >90% of patients
• Median time to remission is approximately 12 months 1
• Long-term relapse rates remain high (up to 50% within 5 years)

Common Pitfalls to Avoid

1. Delayed diagnosis and treatment - can lead to irreversible organ damage
2. Inadequate initial immunosuppression - increases risk of treatment failure
3. Too rapid glucocorticoid tapering - may precipitate disease flares
4. Inadequate infection prophylaxis - especially for Pneumocystis pneumonia
5. Failure to monitor for treatment toxicities - particularly with cyclophosphamide (hemorrhagic cystitis, infertility, malignancy) and glucocorticoids

The treatment approach should be adjusted based on disease severity, organ involvement, and patient-specific factors, with the primary goal of preventing mortality and permanent organ damage while minimizing treatment-related toxicity.