What is the efficacy of rituximab (Rituxan) in treating vasculitis, specifically granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), as shown in the ADVOCATE trial?

From the Guidelines

Rituximab is a highly effective treatment for ANCA-associated vasculitis, including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), as demonstrated by its non-inferiority to cyclophosphamide for induction therapy and superiority to azathioprine for maintenance therapy 1. The ADVOCATE trial, although primarily comparing avacopan to prednisone alongside cyclophosphamide or rituximab, supports the use of rituximab in treating ANCA-associated vasculitis. Key points to consider when using rituximab for ANCA-associated vasculitis include:

• Administration: typically four weekly infusions of 375 mg/m² or two 1000 mg infusions separated by two weeks, followed by maintenance therapy every 4-6 months for 2-5 years depending on disease severity and relapse risk.
• Mechanism: depleting B cells, which produce autoantibodies driving vasculitis pathogenesis.
• Efficacy: non-inferior to cyclophosphamide for induction therapy and superior to azathioprine for maintenance therapy, with remission rates of approximately 60-80% at 6 months 1.
• Patient considerations: screen for hepatitis B before starting treatment, provide pneumocystis pneumonia prophylaxis, and monitor immunoglobulin levels during long-term therapy due to the risk of hypogammaglobulinemia.
• Benefits: particularly beneficial for patients with relapsing disease, those desiring to preserve fertility, and those with contraindications to cyclophosphamide. It is essential to note that while the ADVOCATE trial primarily focused on avacopan, the existing body of evidence, including the RAVE trial, supports the efficacy of rituximab in treating ANCA-associated vasculitis 1.

From the Research

ADVOCATE Trial Overview

The ADVOCATE trial is not directly mentioned in the provided evidence. However, the efficacy of rituximab in treating vasculitis, specifically granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), can be summarized as follows:

Efficacy of Rituximab

• Rituximab has been shown to be effective in inducing remission in patients with GPA and MPA, with a complete remission rate of 64% at 6 months, compared to 55% with cyclophosphamide 2.
• A prospective observational cohort study demonstrated that rituximab and glucocorticoids can induce remission in 90% of patients with relapsing ANCA-associated vasculitis by 4 months 3.
• Rituximab has been compared to azathioprine for maintaining remission in the MAINRITSAN trial and may be more efficacious in maintaining remission in patients treated with cyclophosphamide induction 4.

Safety Profile

• Rituximab has a different and less frequent adverse effect profile compared to cyclophosphamide, with more frequent infections, thrombocytopenia, diarrhea, peripheral edema, cough, and cardiovascular disorders 2.
• The safety profile of rituximab is similar to that of cyclophosphamide in randomized control trials, but its use can be considered over cyclophosphamide in patients who have relapsing or refractory disease or in young patients seeking to preserve fertility 4.

Key Findings

• Rituximab is a non-inferior alternative to standard cyclophosphamide-based therapy for induction of remission in GPA and MPA 2, 4.
• Rituximab may be more efficacious in maintaining remission in patients treated with cyclophosphamide induction 4.
• Rituximab can induce remission in patients with relapsing ANCA-associated vasculitis, with a high level of efficacy and a similar safety profile to previous studies 3.