From the Guidelines
Wegener's granulomatosis, now called Granulomatosis with Polyangiitis (GPA), should be treated with a combination of corticosteroids and immunosuppressants, with rituximab (375 mg/m² weekly for 4 weeks) or cyclophosphamide (either oral at 2 mg/kg/day or intravenous pulses) as the preferred initial therapy, according to the 2021 American College of Rheumatology/Vasculitis Foundation guideline 1.
Treatment Overview
The treatment approach for GPA involves:
- Initial therapy with high-dose prednisone (1 mg/kg/day, maximum 80 mg daily) combined with rituximab or cyclophosphamide
- Maintenance therapy with less toxic agents like azathioprine (2 mg/kg/day), methotrexate (20-25 mg weekly), or mycophenolate mofetil (2 g/day) for at least 18-24 months
- Pneumocystis pneumonia prophylaxis with trimethoprim-sulfamethoxazole during immunosuppressive therapy
- Regular monitoring of kidney function, complete blood counts, and ANCA levels
Key Considerations
- The 2022 EULAR algorithm for treatment of GPA recommends the use of rituximab over cyclophosphamide in patients with childbearing potential or previous exposure to cyclophosphamide at an individual cumulative dosage considered to be associated with an increased risk of complications 1
- Mepolizumab (300 mg every 4 weeks) may be considered for maintenance of remission in patients with relapsing or refractory GPA without organ-threatening manifestations at the time of relapse 1
- Plasma exchange may be considered for patients with active glomerulonephritis who are at a higher risk of progression to end-stage renal disease, but the routine addition of plasma exchange to remission induction therapy is not recommended 1
From the Research
Definition and Treatment of Wegener's Granulomatosis
- Wegener's granulomatosis (WG) is a systemic vasculitis that involves the upper respiratory tract, lower respiratory tract, and kidney, with varying degrees of disseminated vasculitis 2.
- The principal aims of therapy are to control the disease swiftly, limit the extent and severity of permanent organ damage, and minimize the short-term and long-term morbidities that often result from therapy 3, 4.
Treatment Strategies
- Cyclophosphamide (CYC) plus corticosteroids (CS) is the mainstay of therapy for generalized, multisystemic WG 2.
- Short-course (3-6 months) induction treatment with CYC plus CS, followed by maintenance therapy with less toxic agents (e.g., methotrexate, azathioprine) is recommended 2.
- Methotrexate combined with CS may be adequate for limited, non-life threatening WG 2.
- Rituximab, a monoclonal antibody that targets CD20+ B-cells, has been shown to be effective in inducing remission in refractory WG 5, 6.
Refractory Wegener's Granulomatosis
- Standard therapy for WG is often associated with substantial toxicity and may not always be effective 5.
- Rituximab has been proposed as a salvage therapy for refractory disease, with encouraging results in a prospective, open-label pilot trial 5.
- The use of rituximab in refractory WG is being investigated, and it may offer a new treatment option for patients who do not respond to conventional therapy 6.