1. For the treatment of ANCA-associated vasculitis, avacopan was non-inferior to prednisone taper for the number of remissions at week 26.
2. Avacopan was superior to prednisone taper for sustained remission at week 52.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a life-threatening vasculitis. The current standard of care treatments for patients includes cyclophosphamide or rituximab and a prednisone regimen. One of the disease mechanisms is the activation of the alternative complement system, and avacopan is a C5a receptor antagonist. In this study, patients with ANCA-associated vasculitis were randomized either to avacopan or a prednisone taper. The patients were scored according to the Birmingham Vasculitis Activity Score (BVAS). Remission was defined as score of 0. At week 26, avacopan was non-inferior to prednisone taper for the number of remissions. At week 52, avacopan was superior to prednisone. Serious adverse events, not related to vasculitis worsening, was similar between both groups. Limitations in the trial included that steroids were used in the avacopan group, which was about one third the dose of the prednisone group. Overall, this trial demonstrated that avacopan is an option for the treatment of ANCA-associated vasculitis as opposed to prednisone for patients who have an indication for cyclophosphamide or rituximab.
In-Depth [ randomized controlled trial]: This was a phase 3, randomized, placebo-controlled trial of 331 patients randomized to either avacopan or prednisone. Eligible patients included those with ANCA-associated vasculitis with an indication for cyclophosphamide or rituximab, including newly diagnosed or relapsing granulomatosis with polyangiitis or microscopic polyangiitis. Patients who received more than three grams of intravenous glucocorticoids within four weeks were excluded from the study. All patients received either cyclophosphamide or rituximab. The first primary endpoint was remission defined by a BVAS score of 0 at week 26. Avacopan (72.3%) was non-inferior to prednisone taper (70.1%) at week 26 (95% confidence interval [CI], -6.0 to 12.8, P < 0.001 for noninferiority; P = 0.24 for superiority). Avacopan (65.7%) was superior to prednisone taper (54.9%) at week 52 for sustained remission (95% CI, 2.6 to 22.3, P = 0.007 for superiority). Serious adverse events, not related to vasculitis-worsening, were similar between both groups (avacopan, 37.3; prednisone taper, 39.0%). Adverse events potentially related to glucocorticoid use were more frequent in the prednisone group (80.5%) compared to the treatment group (66.3%; difference, -14.2 percentage points; 95% CI, -23.7 to -3.8). Overall, avacopan is an appropriate alternative to prednisone taper in the treatment regimen for ANCA-associated vasculitis that may reduce steroid adverse events without any significant increase in infections.
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