POS-444 EFFECT OF AVACOPAN, A SELECTIVE C5A RECEPTOR INHIBITOR, ON KIDNEY FUNCTION IN PATIENTS WITH ANCA-ASSOCIATED VASCULITIS

Abstract

Patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis and renal disease have a poor prognosis. The effect of avacopan, an oral C5a receptor inhibitor, on renal function is described. The ADVOCATE Phase 3 trial randomized patients to receive avacopan or prednisone taper on a background of either cyclophosphamide (followed by azathioprine) or rituximab. Primary endpoints were remission at Week 26 and sustained remission at Week 52. Secondary objectives included evaluation of kidney function. At Week 52, the difference in eGFR recovery in patients with eGFR <60 mL/min/1.73 m2and/or urinary abnormalities at baseline between avacopan and prednisone treatment groups was 5.5 mL/min/1.73 m2(95% CI [1.4, 9.6], p<0.01) (Figure 1A ). Improvement in eGFR with avacopan was most prominent in patients with eGFR <30 mL/min/1.73 m2at baseline, when by week 52, the least squares mean (LSM) increase in eGFR was 13.7 (avacopan group) vs. 8.2 mL/min/1.73 m2(prednisone group) (p<0.01) (Figure 1B) . Among patients with CKD Stage 4 at baseline: in the avacopan group (n=52), 26 (50%) improved 1 stage and 3 (5.8%) improved 2 stages; in the prednisone group (n=48), 21 (44%) improved 1 stage and 1 (2.1%) improved 2 stages (p=0.32). Avacopan was also associated with more rapid reduction in proteinuria and hematuria. Urinary albumin:creatinine ratio improved 40% within the first 4 weeks of treatment with avacopan vs. no change in the prednisone group (difference -40, 95% CI [-53, -22]). Figure 1. Change in Renal Function Through Week 52 In ADVOCATE, patients with ANCA-associated vasculitis in the avacopan group had greater recovery of kidney function compared to patients in the prednisone group, especially among patients with CKD Stage 4 and those with eGFR <60 mL/min/1.73 m2and/or urinary abnormalities at baseline.