What is the treatment for Antineutrophil Cytoplasmic Antibody (ANCA) positive vasculitis?

From the Guidelines

The treatment of ANCA-positive vasculitis should involve induction therapy with a combination of high-dose corticosteroids and either rituximab or cyclophosphamide, followed by maintenance therapy with less toxic agents such as azathioprine, methotrexate, or mycophenolate mofetil, as recommended by the most recent guidelines 1. The choice of induction therapy depends on the severity of the disease, with rituximab preferred in relapsing disease and cyclophosphamide considered for patients with organ-threatening or life-threatening disease. Some key points to consider in the treatment of ANCA-positive vasculitis include:

• The use of glucocorticoids, with a starting dose of 50-75 mg prednisolone equivalent/day, and a stepwise reduction according to clinical guidelines 1
• The consideration of avacopan in combination with rituximab or cyclophosphamide as part of a strategy to substantially reduce exposure to glucocorticoids 1
• The potential use of plasma exchange for patients with severe renal involvement or pulmonary hemorrhage 1
• The importance of maintaining remission with less toxic agents, such as azathioprine, methotrexate, or mycophenolate mofetil, and considering rituximab as an alternative 1
• The need for regular monitoring of disease activity, medication side effects, and complications, as well as the provision of Pneumocystis pneumonia prophylaxis with trimethoprim-sulfamethoxazole (or alternatives if contraindicated) 1. It is also important to note that the treatment approach may vary depending on the specific type of ANCA-positive vasculitis, such as GPA, MPA, or EGPA, and the presence of organ-threatening or life-threatening manifestations 1. Overall, the treatment of ANCA-positive vasculitis requires a comprehensive and individualized approach, taking into account the severity of the disease, the presence of comorbidities, and the potential risks and benefits of different treatment strategies, as supported by the most recent and highest quality evidence 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 Table 22 Percentage of Patients with GPA/MPA Who Achieved Complete Remission at 6 Months (Intent-to-Treat Population) RITUXAN(n = 99) 64% Cyclophosphamide(n = 98) 53% Treatment Difference(RITUXAN – Cyclophosphamide) 11%

Treatment of ANCA positive vasculitis:

• Rituximab is a treatment option for ANCA positive vasculitis, specifically for Granulomatosis with Polyangiitis (GPA) and Microscopic Polyangiitis (MPA).
• The study demonstrated non-inferiority of RITUXAN to cyclophosphamide for complete remission at 6 months, with 64% of patients achieving complete remission in the RITUXAN group compared to 53% in the cyclophosphamide group.
• The treatment difference between RITUXAN and cyclophosphamide was 11% 2.

From the Research

Treatment Options for ANCA Positive Vasculitis

• Rituximab versus cyclophosphamide for ANCA-associated vasculitis: A study published in 3 found that rituximab was noninferior to cyclophosphamide for remission induction in severe ANCA-associated vasculitis.
• Combination treatment with rituximab, low-dose cyclophosphamide, and plasma exchange for severe ANCA-associated vasculitis: Research published in 4 reported that this combination regimen was effective in achieving disease remission and allowed for rapid tapering of high-dose glucocorticoids.
• Combination therapy with rituximab and cyclophosphamide for remission induction in ANCA vasculitis: A study in 5 found that this combination therapy was efficacious and well-tolerated, with a median time to complete remission of 4 months.

Glucocorticoid Dosage in ANCA-Associated Vasculitis Treatment

• Reduced-dose versus high-dose glucocorticoids added to rituximab on remission induction in ANCA-associated vasculitis: A randomized clinical trial published in 6 found that a reduced-dose glucocorticoid plus rituximab regimen was noninferior to a high-dose glucocorticoid plus rituximab regimen with regard to induction of disease remission at 6 months.
• Long-term follow-up of reduced-dose versus high-dose glucocorticoids added to rituximab on remission induction in ANCA-associated vasculitis: A 2-year follow-up study published in 7 reported that the majority of patients in the reduced-dose group discontinued prednisolone, and serious adverse events were less frequent in the reduced-dose group.

Efficacy and Safety of Treatment Options

• Rituximab-based regimen was more efficacious than the cyclophosphamide-based regimen for inducing remission of relapsing disease, as reported in 3.
• Combination treatment with rituximab, low-dose cyclophosphamide, and plasma exchange was associated with prolonged B cell depletion and low rates of relapse, as found in 4.
• Reduced-dose glucocorticoid plus rituximab regimen was associated with fewer serious adverse events and infections compared to the high-dose glucocorticoid plus rituximab regimen, as reported in 6 and 7.