Treatment of Wegener's Granulomatosis (Granulomatosis with Polyangiitis)
For remission induction of new-onset organ-threatening or life-threatening Granulomatosis with Polyangiitis (GPA), treatment with a combination of glucocorticoids and rituximab is recommended over cyclophosphamide. 1, 2, 3
Disease Classification and Treatment Approach
- GPA is characterized by necrotizing granulomatous vasculitis of the upper and lower respiratory tract, glomerulonephritis, and variable degrees of small-vessel vasculitis 1
- Treatment is divided into two phases: remission induction followed by maintenance therapy 4
- Disease severity determines the appropriate treatment regimen 3
Remission Induction Therapy
For Severe/Organ-Threatening Disease:
- Combination therapy with glucocorticoids plus rituximab is the preferred first-line treatment 1, 2
- Rituximab dosing: 375 mg/m² IV weekly for 4 doses or alternatively 1,000 mg on days 1 and 15 2
- Initial glucocorticoid dosing typically involves prednisone 40-60 mg/day 1, 3
- Cyclophosphamide with glucocorticoids remains an alternative if rituximab is unavailable 1
For Non-Severe Disease:
- Combination of glucocorticoids with methotrexate is recommended 1, 3
- Mycophenolate mofetil with glucocorticoids is an alternative option 1
Remission Maintenance Therapy
- After achieving disease control, maintenance therapy with rituximab consists of 500 mg IV every 6 months 2
- The MAINRITSAN protocol recommends 500 mg at complete remission and then at months 6,12, and 18 2
- Azathioprine is preferred over mycophenolate mofetil if rituximab is not used 1
- Trimethoprim/sulfamethoxazole (800/160 mg twice daily) can be added to standard maintenance therapy to reduce risk of relapse 1
Treatment of Relapses
- For severe relapses (life- or organ-threatening), treat according to the same guidelines as for initial therapy 1
- For non-severe relapses, reinstitute immunosuppressive therapy or increase its intensity with agents other than cyclophosphamide 1
- Rituximab may be more effective than cyclophosphamide for remission induction in patients with relapsing disease 1
Treatment of Refractory Disease
- For disease resistant to cyclophosphamide and corticosteroids, adding rituximab is recommended 1
- Alternative options include intravenous immunoglobulin or plasmapheresis 1
- TNF-blockade (infliximab) has shown promise in some refractory cases 5
Adjunctive Treatments
- Prophylaxis against Pneumocystis jirovecii pneumonia with trimethoprim/sulfamethoxazole is recommended during immunosuppressive therapy 2
- For patients with nasal disease, treatment with topical antibiotics such as mupirocin may be considered for chronic carriage of nasal Staphylococcus aureus 1
Monitoring and Follow-up
- Regular assessment of disease activity and treatment response is essential 3
- Changes in ANCA titer alone should not guide changes in immunosuppression 1
- Monitor for medication side effects, especially with long-term corticosteroid use 3
Special Considerations
- Rituximab may be particularly preferred over cyclophosphamide in patients who wish to preserve fertility 2
- Before initiating rituximab, screen all patients for HBV infection by measuring HBsAg and anti-HBc 6
- For patients considering renal transplantation, it is recommended to delay transplantation until patients are in complete extrarenal remission for 12 months 1
The treatment of GPA has evolved significantly from the days when mortality was extremely high. With current treatment regimens, long-term remission can be achieved in the majority of patients, though careful monitoring and management of potential treatment complications remain essential.