Avacopan’s Superiority for ANCA-Associated Vasculitis Persists Despite Low eGFR

Patients with ANCA-associated vasculitis and an eGFR of 20 mL/min/1.73 m2 or less experienced significant improvements in eGFR with avacopan vs prednisone. Source: Getty Images

Avacopan, an orally administered C5a receptor inhibitor approved for treating adults with antineutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitis, improves kidney function better than prednisone among patients with severe renal insufficiency, according to a recent study.

The finding is from a subgroup analysis of patients in the phase 3 ADVOCATE trial who had an estimated glomerular filtration rate (eGFR, in mL/min/1.73 m²) of 20 or less. The trial included 330 patients with ANCA-associated vasculitis (of whom 81% had renal involvement) randomly assigned to receive avacopan (166 patients) or prednisone (164 patients). In the original trial, eGFR increased on average by 7.3 in the avacopan group compared with 4.1 in the prednisone group.

The subgroup analysis included 50 patients who had an eGFR of 20 or less (27 in the avacopan group (16%) and 23 in the prednisone arm (14%). The groups had a mean eGFR at baseline of 17.6 and 17.5, respectively.

At week 52, eGFR increased an average of 16.1 in the avacopan recipients compared with 7.7 in the prednisone recipients, a significant difference between the groups, Frank B. Cortazar, MD, of the New York Nephrology Vasculitis and Glomerular Center at Saint Peter’s Hospital-Albany in Albany, New York, and colleagues reported in Kidney International Reports.

The last eGFR value obtained during the 52-week treatment period was at least 2-fold higher compared with baseline in 41% and 13% of the avacopan and prednisone arms, respectively, also a significant difference.

Serious adverse events occurred in 13 avacopan recipients (48%) and 16 prednisone recipients (70%).

Study findings raise the question of whether avacopan could benefit patients presenting with an eGFR below 15, according to the investigators. “These patients have the highest risk for end-stage kidney disease and mortality, and are in need of effective therapies that reduce these risks and their downstream consequences,” Dr Cortazar’s team wrote. “The data presented here further support the need to study this more severe subgroup who may have much to gain from avacopan.”

Reference

Cortazar FB, Niles JL, Jayne DRW, et al. Renal recovery for patients with antineutrophil cytoplasmic autoantibody-associated vasculitis and low estimated GFR in the ADVOCATE trial of avacopan. Kidney Int Rep. Published online February 2, 2023. doi:10.1016/j.ekir.2023.01.039