386 Avacopan versus prednisone taper in newly diagnosed or relapsing granulomatosis with polyangiitis or microscopic polyangiitis in the ADVOCATE trial

Abstract Background and Aims In granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), two types of antineutrophil cytoplasmic autoantibody-associated vasculitis, relapses are common, with 14–44% of patients experiencing a relapse at 18–36 months, depending on patient characteristics, duration of follow-up, and maintenance treatment [1]. In the phase 3 ADVOCATE trial, 69% of patients were newly diagnosed and 31% had relapsing GPA/MPA [2]. This post hoc subgroup analysis of ADVOCATE evaluates the safety and efficacy of avacopan compared with a prednisone taper in patients with newly diagnosed or relapsing GPA/MPA. Method ADVOCATE, a randomised, double-blind, double-dummy, active-controlled clinical trial, assigned eligible patients 1:1 to receive avacopan or a prednisone taper on a background of either cyclophosphamide (followed by azathioprine or mycophenolate mofetil) or rituximab. Data from patients with newly diagnosed (N = 229) or relapsing (N = 101) GPA/MPA were analysed. Key outcomes were the percentage of patients achieving remission at week 26 and sustained remission at week 52. Other outcomes included relapse rate, change in estimated glomerular filtration rate (eGFR), urinary albumin to creatinine ratio (UACR), glucocorticoid dose (prednisone-equivalent), Glucocorticoid Toxicity Index (GTI), health-related quality of life (HRQoL), and safety. Results Baseline characteristics were comparable between the avacopan and prednisone taper arms within each disease status group (Table 1). Efficacy outcomes are reported in Table 2. At week 26, similar proportions of patients with newly diagnosed GPA/MPA achieved remission in the avacopan and prednisone taper arms (66.1% vs 66.7%; difference [95% confidence interval (CI)]: −0.6% [−12.8, 11.7]). In the relapsed group, a numerically higher proportion of patients receiving avacopan than those receiving a prednisone taper achieved remission at week 26 (86.3% vs 78.0%; difference [95% CI]: 8.3% [−6.6, 23.1]). Compared with the prednisone taper arm, the proportion of patients who achieved sustained remission at week 52 with avacopan was similar in newly diagnosed GPA/MPA (60.9% vs 57.9%; difference [95% CI]: 3.0% [−9.7, 15.7]) and higher in relapsed GPA/MPA (76.5% vs 48.0%; difference [95% CI]: 28.5% [10.4, 46.6]). The relapse rate over 52 weeks after remission at any time was lower with avacopan than with a prednisone taper in both newly diagnosed (8.2% vs 18.2%) and relapsed (14.6% vs 27.7%)