From the Guidelines
For patients with ANCA-associated vasculitis, rituximab is recommended as the first-line treatment for induction of remission, especially in those with relapsing disease or PR3-ANCA positivity, due to its superior remission rates and lower risk of infectious complications compared to cyclophosphamide 1.
Treatment Overview
The treatment of ANCA-associated vasculitis typically involves a combination of induction therapy with high-dose corticosteroids and either rituximab or cyclophosphamide.
- Induction therapy:
- Rituximab (375 mg/m² weekly for 4 weeks)
- Cyclophosphamide (oral 2 mg/kg/day or IV 15 mg/kg every 2-3 weeks)
- Maintenance therapy:
- Lower-dose steroids tapered over months
- Either azathioprine (2 mg/kg/day), methotrexate (20-25 mg weekly), or rituximab (500 mg every 6 months)
Key Considerations
- Rituximab is preferred over cyclophosphamide for patients with relapsing disease or PR3-ANCA positivity, due to its superior remission rates and lower risk of infectious complications 1.
- Avacopan, an oral C5a receptor antagonist, may be considered as an alternative to glucocorticoids for induction of remission, especially in patients with severe disease or those who are unable to tolerate glucocorticoids 1.
- Plasma exchange may be considered for severe disease with pulmonary hemorrhage or rapidly progressive glomerulonephritis 1.
- Supportive care includes pneumocystis pneumonia prophylaxis with trimethoprim-sulfamethoxazole, bone health protection, and blood pressure control.
Disease Management
- Structured clinical assessment should inform decisions on changes in treatment, rather than relying solely on ANCA and/or CD19+ B cell testing 1.
- Treatment duration typically lasts 18-24 months, with monitoring for disease activity and medication side effects.
- Longer duration of therapy should be considered in relapsing patients or those with an increased risk of relapse, but should be balanced against patient preferences and risks of continuing immunosuppression 1.
From the FDA Drug Label
A total of 197 patients with active, severe GPA and MPA (two forms of ANCA Associated Vasculitides) were treated in a randomized, double-blind, active-controlled, multicenter, non-inferiority study, conducted in two phases – a 6 month remission induction phase and a 12 month remission maintenance phase. The main outcome measure for both GPA and MPA patients was achievement of complete remission at 6 months defined as a BVAS/GPA of 0, and off glucocorticoid therapy The study demonstrated non-inferiority of RITUXAN to cyclophosphamide for complete remission at 6 months As shown in Table 22, the study demonstrated non-inferiority of RITUXAN to cyclophosphamide for complete remission at 6 months Rate64% of patients in the RITUXAN group achieved complete remission at 6 months, compared to 53% of patients in the cyclophosphamide group
Rituximab is effective in treating ANCA-associated vasculitis, with 64% of patients achieving complete remission at 6 months, compared to 53% of patients treated with cyclophosphamide 2.
- Key findings:
- Non-inferiority of rituximab to cyclophosphamide for complete remission at 6 months
- 64% of patients in the rituximab group achieved complete remission at 6 months
- Rituximab is a viable treatment option for ANCA-associated vasculitis
- Safety profile: The safety profile of rituximab in ANCA-associated vasculitis is consistent with its safety profile in RA and GPA/MPA, with common adverse reactions including infusion-related reactions and infections 2.
From the Research
Overview of ANCA-Associated Vasculitis
- ANCA-associated vasculitis (AAV) is a systemic, potentially organ and life-threatening chronic autoimmune disease 3
- The disease is characterized by the presence of antineutrophil cytoplasmic antibodies (ANCA) and can affect various organs, including the kidneys, lungs, and skin 4
Treatment Options
- Current management strategies for AAV include high-dose glucocorticoids in combination with cyclophosphamide or rituximab, with overall remission rates of 70-90% 3
- Rituximab is considered a preferable option for both induction and maintenance of remission 4
- Regimens with less glucocorticoids are equally effective and safer in inducing remission compared with conventional regimens 5, 4
- Avacopan is an effective glucocorticoid-sparing option 4
Role of Glucocorticoids
- Glucocorticoids are a mainstay of treatment for AAV, but their use is associated with significant toxicity 6, 3, 7
- The Glucocorticoid Toxicity Index (GTI) can be used to quantify glucocorticoid-related toxicity and guide treatment decisions 7
- Higher cumulative doses of steroids are associated with worse glucocorticoid-related toxicity 7
Plasma Exchange
- There is no compelling evidence to support the routine use of plasma exchange in addition to standard remission-induction therapy in AAV 5, 4