From the Guidelines
Wegener's granulomatosis, now known as granulomatosis with polyangiitis (GPA), should be treated with a combination of corticosteroids and immunosuppressants, with rituximab (375 mg/m² weekly for 4 weeks) being the preferred option over cyclophosphamide for remission induction, as recommended by the 2021 American College of Rheumatology/Vasculitis Foundation guideline 1.
Treatment Approach
The treatment approach for GPA typically involves a combination of high-dose prednisone (1 mg/kg/day, maximum 80 mg daily) and an immunosuppressant, such as rituximab or cyclophosphamide.
- Induction therapy usually lasts 3-6 months until remission is achieved.
- Maintenance therapy follows with less toxic medications like azathioprine (2 mg/kg/day), methotrexate (20-25 mg weekly), or mycophenolate mofetil (2 g/day) for at least 18-24 months.
Disease Characteristics
GPA is characterized by the presence of anti-neutrophil cytoplasmic antibodies (ANCA), particularly those targeting proteinase 3, which contribute to the inflammatory process by activating neutrophils that damage blood vessel walls 1.
Treatment Recommendations
The 2021 American College of Rheumatology/Vasculitis Foundation guideline recommends the following treatment approach for GPA:
- Remission induction therapy: rituximab (375 mg/m² weekly for 4 weeks) or cyclophosphamide (either oral at 2 mg/kg/day or intravenous pulses) 1.
- Remission maintenance therapy: azathioprine (2 mg/kg/day), methotrexate (20-25 mg weekly), or mycophenolate mofetil (2 g/day) for at least 18-24 months 1.
Important Considerations
Trimethoprim-sulfamethoxazole may be added to prevent Pneumocystis pneumonia and potentially reduce relapse risk 1. The disease can be life-threatening if left untreated, with potential complications including kidney failure, lung damage, and cardiovascular problems 1.
From the Research
Definition and Treatment of Wegener's Granulomatosis
- Wegener's granulomatosis (WG) is a form of systemic vasculitis that typically involves the kidneys and upper and lower respiratory tract 2.
- The treatment of WG aims to limit the extent and severity of permanent organ damage by controlling the disease promptly and to minimize the short- and long-term morbidity that often results from therapy 3.
- The mainstay of therapy for generalized, multisystemic WG is cyclophosphamide (CYC) plus corticosteroids (CS), but concern about late toxicities associated with CYC has led to novel treatment approaches 2.
Treatment Strategies
- Current treatment strategies involve a short-course (3-6 months) induction treatment with CYC plus CS, followed by maintenance therapy with less toxic agents (e.g., methotrexate, azathioprine) 2.
- Rituximab, a chimeric anti-CD20 antibody, has been shown to be effective in inducing remission in patients with refractory WG 4, 5, 6.
- Leflunomide maintenance may increase the efficacy of rituximab and prolong the disease-free period 4.
Clinical Manifestations and Pathogenesis
- Clinical manifestations of WG are protean, and virtually any organ can be involved 2.
- The pathogenesis of WG has not been elucidated, but both cellular and humoral components are involved, and circulating antineutrophil cytoplasmic antibodies (cANCA) likely play a role in the pathogenesis and often correlate with activity of the disease 2.