From the Guidelines
Rituximab is the preferred therapy for suppressing the autoimmune response to PR3, particularly for patients with known relapsing disease, PR3-AAV, and azathioprine allergy, due to its efficacy in preventing relapses and improving health-related quality of life, as shown in the MAINRITSAN study 1.
Key Considerations
- The choice of therapy should be based on the individual patient's risk of relapse, with patients having a prior history of relapse and PR3-ANCA being at higher risk 1.
- Maintenance therapy should be given to all patients after induction of remission, with the goal of preventing relapses and minimizing adverse events 1.
- The duration of maintenance therapy should be tailored to the individual patient's risk of relapse, with some patients requiring longer durations of therapy 1.
Treatment Options
- Rituximab (500 mg every 6 months) is a preferred option for maintenance therapy, due to its efficacy in preventing relapses and improving health-related quality of life 1.
- Azathioprine (2 mg/kg/day) is an alternative option for maintenance therapy, although it may have a higher risk of relapse compared to rituximab 1.
- Methotrexate (20-25 mg weekly) may be used for induction therapy in less severe disease, although its efficacy in maintenance therapy is less well established 1.
Monitoring and Adjustments
- Regular monitoring of blood counts, liver and kidney function, and disease activity markers is essential during treatment to adjust dosing and prevent complications 1.
- The dose and duration of therapy should be adjusted based on the individual patient's response to treatment and risk of relapse 1.
From the Research
Therapy Suppressing the Autoimmune Response to PR3
- The studies 2, 3, 4, 5, 6 provide evidence on various therapies used to suppress autoimmune responses, including those related to PR3.
- Rituximab, a B-cell depleting agent, has been shown to be effective in inducing remission in patients with granulomatosis with polyangiitis (GPA) 2 and primary membranous nephropathy 3.
- The combination of rituximab with other immunosuppressive agents, such as cyclophosphamide and prednisone, has been found to be effective in achieving complete remission in patients with primary membranous nephropathy 3.
- A Bayesian network meta-analysis of randomized controlled trials found that rituximab was associated with lower relapse rates compared to other immunosuppressive agents, such as mycophenolate mofetil and methotrexate, in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) 4.
- First-line use of rituximab combined with short-term prednisone has been shown to be more effective than prednisone alone in achieving complete remission off-therapy in patients with pemphigus 5.
- Synthetic drugs, such as hydroxychloroquine, azathioprine, and mycophenolate mofetil, are commonly used to treat systemic lupus erythematosus (SLE) and have been found to be effective in ameliorating symptoms and positively influencing outcome 6.
Mechanism of Action
- Rituximab works by depleting B-cells, which are involved in the production of autoantibodies, such as those against PR3 2, 3, 4, 5.
- Cyclophosphamide and prednisone work by suppressing the immune system and reducing inflammation 3.
- Azathioprine and mycophenolate mofetil work by inhibiting the proliferation of T-cells and B-cells, which are involved in the autoimmune response 4, 6.
- Hydroxychloroquine works by reducing the production of autoantibodies and inhibiting the activation of immune cells 6.