Treatment of ANCA-Associated Vasculitis With Avacopan: Results of the ADVOCATE Trial After Readjudication of the Primary Endpoint

Background The ADVOCATE trial evaluated treatment with avacopan for granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Concerns regarding the 2019 primary outcome adjudication procedures in nine participants prompted readjudication in 2026 of primary outcomes for all participants. Methods Patients with GPA/MPA were randomized 1:1 to prednisone taper or avacopan 30 mg twice daily; participants received treatment with cyclophosphamide or rituximab. An independent, blinded committee readjudicated the primary outcomes of remission at week 26 and sustained remission at week 52. Noninferiority and superiority were established if lower bounds of the 95% confidence interval (CI) for difference in rates were greater than -20.0 and 0.0 percentage points, respectively. Secondary outcomes included glucocorticoid exposure and toxicity, kidney parameters, health-related quality of life, and safety. Results Among 330 participants, remission at week 26 was achieved by 68.1% and 67.1% in the avacopan and prednisone groups, respectively, in the 2026 readjudication (adjusted difference: 2.2%; 95% CI, -7.5, 11.9), compared with 72.3% and 70.1% in the 2019 adjudication (adjusted difference: 3.4%; 95% CI, -6.0, 12.8). Sustained remission at week 52 was achieved by 61.4% and 52.4%, respectively, in the 2026 readjudication (adjusted difference: 9.8%; 95% CI, -0.3, 19.9), compared with 65.7% and 54.9% in the 2019 adjudication (adjusted difference: 12.5%; 95% CI, 2.6, 22.3). Secondary endpoints favored the avacopan group. Conclusions Treatment of GPA/MPA with avacopan in combination with rituximab or cyclophosphamide, when compared with a prednisone taper, resulted in similarly high rates of remission and sustained remission, but reductions in glucocorticoid exposure and toxicity.