From the Guidelines
The treatment of choice for Wegener's disease, also known as Granulomatosis with Polyangiitis (GPA), is rituximab over cyclophosphamide for remission induction in patients with active, severe disease, as conditionally recommended by the 2021 American College of Rheumatology/Vasculitis Foundation guideline 1.
Overview of Treatment Approach
The management of GPA involves a combination of corticosteroids and immunosuppressive agents, with the goal of inducing remission and maintaining it to improve morbidity, mortality, and quality of life.
- Initial therapy for active, severe GPA typically involves high-dose glucocorticoids (GCs) combined with either rituximab or cyclophosphamide for remission induction.
- The choice between rituximab and cyclophosphamide depends on the severity of the disease and patient-specific factors, with rituximab being conditionally recommended over cyclophosphamide for remission induction in patients with active, severe GPA/MPA 1.
Induction Therapy
- Rituximab is administered as an alternative to cyclophosphamide for remission induction, especially in patients with severe disease, due to its conditional recommendation over cyclophosphamide 1.
- Cyclophosphamide can be given orally or intravenously, but its use is now more reserved due to the preference for rituximab in severe cases.
- High-dose GCs, either intravenous pulse or high-dose oral, are used as part of the initial therapy, with a reduced-dose GC regimen conditionally recommended over a standard-dose regimen for remission induction 1.
Maintenance Therapy
- After achieving remission, maintenance therapy with less toxic agents like methotrexate, azathioprine, or mycophenolate mofetil is recommended for at least 18-24 months.
- Rituximab is conditionally recommended over methotrexate or azathioprine for remission maintenance in patients with severe GPA/MPA whose disease has entered remission after treatment with cyclophosphamide or rituximab 1.
- The duration of non-GC remission maintenance therapy and GC therapy should be guided by the patient’s clinical condition, preferences, and values 1.
Special Considerations
- In patients with GPA/MPA receiving remission maintenance therapy with rituximab who have hypogammaglobulinemia and recurrent severe infections, immunoglobulin supplementation is conditionally recommended 1.
- For patients with active, nonsevere GPA, methotrexate and GCs are conditionally recommended as the initial treatment, offering a balance between efficacy and toxicity 1.
Conclusion of Recommendations
Given the complexity and variability of GPA, treatment must be individualized, considering the severity of the disease, organ involvement, and patient preferences. The guidelines 1 provide a framework for managing GPA, emphasizing the importance of rituximab in the treatment of severe disease and the role of maintenance therapy in preventing relapses and improving long-term outcomes.
From the FDA Drug Label
- 4 Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA) RITUXAN, in combination with glucocorticoids, is indicated for the treatment of adult and pediatric patients 2 years of age and older with Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA). The treatment of choice for Wegener's disease (also known as Granulomatosis with Polyangiitis or GPA) is RITUXAN in combination with glucocorticoids 2.
- Key points:
- RITUXAN is indicated for the treatment of adult and pediatric patients 2 years of age and older with GPA (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA).
- The treatment should be administered in combination with glucocorticoids.
From the Research
Treatment Options for Wegener's Disease
The treatment of choice for Wegener's disease, also known as granulomatosis with polyangiitis (GPA), depends on the severity of the disease.
- For patients with active but non-severe GPA, methotrexate and glucocorticoids can induce and maintain remission 3.
- For patients with severe disease, options include glucocorticoids combined with either cyclophosphamide or rituximab 3.
- Cyclophosphamide (CYC) plus corticosteroids (CSs) is the mainstay of therapy for generalized, multisystemic GPA, with a recommended short-course (3 to 6 months) induction treatment followed by maintenance therapy with less toxic agents such as methotrexate or azathioprine 4.
- Rituximab may be useful for induction therapy or CYC-refractory GPA, and has been shown to be as effective as cyclophosphamide in inducing remission of severe active GPA 3, 5, 6.
Maintenance Therapy
Maintenance therapy is an important aspect of treating GPA, with the goal of preventing relapse and minimizing toxicity.
- Methotrexate combined with CS may be adequate for limited, non-life-threatening GPA 4.
- The addition of a conventional maintenance agent to rituximab and glucocorticoids has been shown to decrease the incidence of relapse without increasing adverse events 5.
- Low-dose rituximab maintenance treatment has been associated with low rates of relapse and a favorable safety profile 6.
Special Considerations
Certain patient populations may require special consideration when selecting a treatment regimen.
- Patients with relapsing disease who have had prior cyclophosphamide exposure may benefit from rituximab therapy 3.
- Patients with alveolar hemorrhage requiring mechanical ventilation or rapidly progressive glomerulonephritis requiring dialysis may require cyclophosphamide due to limited experience with rituximab in these settings 3.