#386 Avacopan versus prednisone taper in newly diagnosed or relapsing granulomatosis with polyangiitis or microscopic polyangiitis in the ADVOCATE trial
Authors: Kronbichler Andreas , Geetha Duvuru , Bray Sarah , Gurlin Rachel E , Merkel Peter A , Jayne David R W 
Published: May 2024

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%) GPA/MPA. There was a larger improvement in eGFR over 52 weeks (newly diagnosed: 8.1 vs 5.3; relapsed: 5.0 vs 0.7) and earlier reduction in UACR at 4 weeks (newly diagnosed: −42% vs −1%; relapsed: −32% vs 3%) in the avacopan arm than in the prednisone taper arm. The total all-source median glucocorticoid dose was 625 mg in the avacopan arm compared with 3048 mg in the prednisone taper arm for newly diagnosed GPA/MPA, and 500 mg in the avacopan arm compared with 3139 mg in the prednisone taper arm for relapsed GPA/MPA. At week 26, the GTI cumulative worsening and aggregate improvement scores were lower (more favourable) with avacopan than with a prednisone taper in both arms. The change from baseline in both analysed HRQoL scales was numerically higher with avacopan than with a prednisone taper at week 52 in both groups (Table 2). Fewer adverse events per patient were reported with avacopan vs a prednisone taper in both disease status groups (Table 1).

Conclusion
In this post hoc subgroup analysis of the ADVOCATE trial, efficacy and safety outcomes in patients with newly diagnosed or relapsed GPA/MPA favoured avacopan compared with a prednisone taper, supporting the use of avacopan in these patient types. The observed clinical efficacy of avacopan especially in patients with relapsing GPA/MPA provides valuable insights into the treatment of this difficult-to-treat subgroup.