From the Guidelines
Vasculitis treatment should prioritize the use of rituximab alongside corticosteroids for ANCA-associated vasculitis, as recommended by the most recent guidelines 1.
Key Considerations
- The treatment approach for vasculitis involves a combination of corticosteroids and immunosuppressive medications, with the specific choice depending on the type and severity of the disease.
- For ANCA-associated vasculitis, rituximab has become a first-line therapy, often used in conjunction with corticosteroids like prednisone, starting at a dose of 1 mg/kg/day.
- The treatment typically consists of an induction phase lasting 3-6 months to achieve remission, followed by a maintenance phase of 18-24 months or longer, using lower doses of immunosuppressants such as azathioprine (2 mg/kg/day) or mycophenolate mofetil.
- Regular monitoring of organ function, blood counts, and inflammatory markers is crucial during treatment, and patients should be aware of the signs of infection due to immunosuppression.
- Pneumocystis pneumonia prophylaxis with trimethoprim-sulfamethoxazole is recommended when patients are on significant immunosuppression.
Disease-Specific Recommendations
- For GPA or MPA with organ-threatening or life-threatening disease, treatment with a combination of glucocorticoids and either rituximab or cyclophosphamide is recommended, with rituximab preferred in relapsing disease 1.
- For non-organ-threatening or non-life-threatening GPA or MPA, treatment with a combination of glucocorticoids and rituximab is recommended, with methotrexate or mycophenolate mofetil as alternatives to rituximab.
- For EGPA, treatment approaches vary based on the presence of organ-threatening or life-threatening manifestations, with recommendations including the use of high-dose glucocorticoids, cyclophosphamide, and rituximab for severe cases, and glucocorticoids alone for less severe cases.
Underlying Mechanism and Monitoring
- The underlying mechanism of vasculitis involves immune system dysregulation, with autoantibodies or immune complexes triggering inflammation in vessel walls.
- Regular monitoring and a structured clinical assessment are essential for managing vasculitis, rather than relying solely on ANCA and/or CD19+ B cell testing to inform treatment decisions 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 In the RITUXAN group, 44% of patients achieved CR at 6 and 12 months, and 38% of patients achieved CR at 6,12, and 18 months
Vasculitis Treatment with Rituximab:
- Rituximab has been shown to be effective in treating Granulomatosis with Polyangiitis (GPA) and Microscopic Polyangiitis (MPA), two forms of ANCA-associated vasculitis.
- In a randomized, double-blind, active-controlled study, rituximab demonstrated non-inferiority to cyclophosphamide for complete remission at 6 months.
- The main outcome measure was achievement of complete remission at 6 months, defined as a BVAS/GPA of 0, and off glucocorticoid therapy.
- Key findings include:
- 64% of patients in the rituximab group achieved complete remission at 6 months.
- 44% of patients in the rituximab group achieved complete remission at 6 and 12 months.
- 38% of patients in the rituximab group achieved complete remission at 6,12, and 18 months. 2
From the Research
Definition and Classification of Vasculitis
- Vasculitis refers to a group of inflammatory conditions that affect the blood vessels, leading to severe consequences such as tissue ischemia, structural abnormalities, and end-organ damage 3.
- The different forms of vasculitis are commonly classified based on the size of the blood vessel involved, including large-vessel, medium-vessel, and small-vessel vasculitis 3.
Diagnosis of Vasculitis
- Approaching the diagnosis of vasculitis can be challenging due to the differing clinical presentation and organ manifestations 4.
- Vasculitis is often considered too late, given the heterogeneous presentation and various mimics, highlighting the need for a diagnostic approach to vasculitis 4.
Treatment of Vasculitis
- Glucocorticoids remain the backbone of treatment for systemic vasculitis, but are associated with numerous toxicities 5.
- Biologic and novel small molecule therapies have demonstrated efficacy in sparing glucocorticoids and improving outcomes in various forms of vasculitis, including giant cell arteritis, ANCA-associated vasculitis, and eosinophilic granulomatosis with polyangiitis 5, 6.
- Specific treatments, such as tocilizumab, rituximab, and mepolizumab, have shown promise in refining the mechanistic immunological classification of vasculitis and guiding treatment decisions 5, 6, 7.
Mechanistic Immunological Classification of Vasculitis
- Clinical studies with cytokine and cell-specific drugs are dissecting the heterogeneous immunopathogenic mechanisms of vasculitis and supporting a mechanistic immunological classification 6.
- Cytokine antagonism is pointing towards immunological distinctions between different forms of vasculitis, such as eosinophilic granulomatosis with polyangiitis and granulomatosis with polyangiitis/microscopic polyangiitis 6.