Renal Recovery for Patients with ANCA-Associated Vasculitis and Low eGFR in the ADVOCATE Trial of Avacopan

Predictive Factors of Renal Recovery and Progression to End-Stage Kidney Disease in Patients With Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis With Severe Kidney Disease

“… 24 Cortazar et al. 34 recently showed that among patients with baseline eGFR ≤20 ml/min per 1.73 m 2 in the ADVOCATE (Avacopan for the Treatment of ANCA-Associated Vasculitis) trial, eGFR improved more in the avacopan group when compared to the prednisone group (mean change of eGFR 16.1 vs. 7.7 ml/min per 1.73 m 2 ; P = 0.003; increase in eGFR in ≥2-fold in 40.7% vs. 13.0%; P = 0.030). The integration of these data on the treatment of patients with eGFR <15 ml/min per 1.73 m 2 is likely to change the standard-of-care of patients with severe kidney disease.…”

Use of Avacopan in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and Estimated Glomerular Filtration Rate <15 ml/min per 1.73 m2

“…This remains speculative in the absence of repeated biopsy studies comparing the impact of avacopan versus prednisone on kidney histology. In the cohort from ADVOCATE with eGFR <20 ml/min per 1.73 m 2 , more than 80% of patients had myeloperoxidase-antineutrophil cytoplasmic antibody subtype, 3 which is associated with more glomerulosclerosis, fibrosis, and worse long-term kidney function as compared to proteinase 3-antineutrophil cytoplasmic antibody. 6 Therefore, mitigation of fibrosis with avacopan may explain superior eGFR recovery in this subgroup.…”

“… 2 Avacopan resulted in a significant increase in estimated glomerular filtration rate (eGFR), including the subset of patients with eGFR <20 ml/min per 1.73 m 2 . 3 The ADVOCATE trial excluded patients with eGFR <15 ml/min per 1.73m 2 ; data in this subgroup are currently limited to 1 case series in which all patients required kidney replacement therapy. 4 Here, we report the experience using avacopan at our center in 4 patients with AAV with baseline eGFR <15 ml/min per 1.73 m 2 .…”

Management of antineutrophil cytoplasmic antibody–associated vasculitis with glomerulonephritis as proposed by the ACR 2021, EULAR 2022 and KDIGO 2021 guidelines/recommendations

“…reduced relapse rate within the first 52 weeks and a higher eGFR recovery at Week 26 and 52 when compared with GC tapering [ 52 ]. Cortazar et al [ 54 ] recently showed that among patients with baseline eGFR ≤20 mL/min/1.73 m 2 in the ADVOCATE trial, eGFR improved more in the avacopan group when compared with the prednisone group ( P = .030). Of note, GC use was lower but not absent in avacopan- compared with GC-treated patients (1348.9 ± 2040.29 mg versus 3654.5 ± 1709.83 mg mean total dose ± SD, respectively).…”

“…Clinical trials will continue to help determine how best to use available and new treatments, and in the evaluation of outcomes of interest. It will be interesting to evaluate the performance of avacopan in patients with life-threatening kidney disease: although promising results were recently published by Cortazar et al , these were not available at the time of the EULAR recommendations (presented in June 2022 in Copenhagen), nor were the ADVOCATE trial results published at the time of the publication of the ACR/VCRC and KDIGO guidelines [ 54–56 ]. The KDIGO guidelines for ANCA vasculitis are currently undergoing an update.…”