What is the treatment for Wegener granulomatosis?

Treatment of Granulomatosis with Polyangiitis (Wegener Granulomatosis)

For severe or organ-threatening granulomatosis with polyangiitis, glucocorticoids combined with rituximab is the preferred first-line treatment, with cyclophosphamide as an alternative if rituximab is unavailable. 1

Disease Severity Stratification

Treatment selection depends critically on disease severity:

• Severe/organ-threatening disease includes life-threatening manifestations such as rapidly progressive glomerulonephritis, alveolar hemorrhage, or other organ-threatening vasculitis 1
• Non-severe disease lacks these features but still requires treatment for active disease 1

Remission Induction Therapy

For Severe or Organ-Threatening Disease

Glucocorticoids plus rituximab is the preferred regimen: 1

• Glucocorticoid dosing: Start with prednisone 40-60 mg/day (or equivalent), often preceded by pulse methylprednisolone 500-1000 mg IV daily for 3 days in the most severe cases 1
• Rituximab dosing: 500 mg IV every 6 months for maintenance after induction 1

Cyclophosphamide plus glucocorticoids remains an effective alternative: 2, 1

• Use when rituximab is unavailable or contraindicated 2
• Cyclophosphamide is given at 2 mg/kg/day orally, with dose adjustments for age and renal function 3
• This regimen achieves complete remission in approximately 93% of patients 3

Important consideration: Rituximab may be particularly preferred in patients wishing to preserve fertility, as cyclophosphamide carries significant gonadotoxic risk 1

For Non-Severe Disease

Glucocorticoids combined with methotrexate is recommended: 1

• This approach avoids the toxicities associated with cyclophosphamide in patients without immediately life-threatening disease 2

Maintenance Therapy

After achieving remission, the focus shifts to preventing relapse while minimizing treatment toxicity:

Rituximab maintenance: 500 mg IV every 6 months is the preferred maintenance regimen 1

Alternative maintenance options if rituximab is not used: 1

• Azathioprine is preferred over mycophenolate mofetil 2
• Methotrexate can be used as an alternative 2

Duration of maintenance therapy: Continue for 24-48 months following remission induction in new-onset disease 2

• Longer duration should be considered in relapsing patients or those at increased risk of relapse 2
• Balance this against risks of continued immunosuppression and patient preferences 2

Adjunctive Treatments

Trimethoprim-sulfamethoxazole (800/160 mg twice daily): 1

• Add to standard maintenance therapy to reduce relapse risk 1
• Also provides prophylaxis against Pneumocystis jirovecii pneumonia during immunosuppressive therapy 1

Topical nasal antibiotics (mupirocin): Consider for chronic nasal Staphylococcus aureus carriage in patients with nasal disease 1

Treatment of Relapses

For severe relapses (life- or organ-threatening): Follow the same treatment approach as for initial severe disease 1

Rituximab may be more effective than cyclophosphamide for remission induction in relapsing disease 1

Refractory Disease

For disease resistant to cyclophosphamide and corticosteroids: 1

• Adding rituximab is recommended 1
• Alternative options include intravenous immunoglobulin or plasmapheresis 1

Critical Drug Interactions and Precautions

Cyclophosphamide has significant interactions that can increase toxicity: 4

• Etanercept: In patients with granulomatosis with polyangiitis, adding etanercept to standard treatment including cyclophosphamide was associated with higher incidence of non-cutaneous malignant solid tumors 4
• Protease inhibitors: May increase concentration of cyclophosphamide's cytotoxic metabolites and increase risk of infections and neutropenia 4
• Depolarizing muscle relaxants: Cyclophosphamide causes persistent cholinesterase inhibition; alert anesthesiologists if surgery occurs within 10 days of treatment 4

Monitoring Considerations

Regular assessment of disease activity is essential: 1

• However, changes in ANCA titer alone should not guide immunosuppression changes 1
• Monitor for treatment-related toxicities, particularly with cyclophosphamide (hemorrhagic cystitis, myelosuppression) and glucocorticoids 2

Common Pitfalls to Avoid

• Do not use etanercept as part of standard therapy due to increased malignancy risk when combined with cyclophosphamide 4
• Do not rely solely on ANCA titers to make treatment decisions about changing immunosuppression 1
• Do not delay renal transplantation consideration, but ensure patients are in complete extrarenal remission for 12 months before proceeding 1
• Do not forget Pneumocystis prophylaxis during intensive immunosuppression 1