Abstract: FR-PO651
Renal Recovery for Patients With Baseline eGFR ≤20 in Avacopan ADVOCATE Trial
Session Information
- Glomerular Diseases: Clinical, Outcomes, Trials - II
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1303 Glomerular Diseases: Clinical‚ Outcomes‚ and Trials
Authors
- Cortazar, Frank B., Saint Peter's Hospital, Albany, New York, United States
- Jayne, David R.W., University of Cambridge, Cambridge, Cambridgeshire, United Kingdom
- Bruchfeld, Annette, Karolinska Institutet, Stockholm, Stockholm, Sweden
- Bekker, Pirow, ChemoCentryx Inc, San Carlos, California, United States
Background
In the 330-patient ADVOCATE trial, where 81% of patients with ANCA-associated vasculitis had renal involvement, estimated glomerular filtration rate (eGFR) increased on average 7.3 mL/min/1.73 m2 with avacopan and 4.1 in the prednisone group (P=0.029) at Week 52 (Jayne et al. 2021).
Methods
The aim of this post hoc analysis was to evaluate changes in eGFR in the 50 patients in ADVOCATE who approached the dialysis threshold, i.e., eGFR ≤20 mL/min/1.73 m2.
Results
The mean age was similar to the overall study population (66 vs. 61 years), but with a higher proportion of newly diagnosed (88 vs. 69%), MPO+ (84 vs. 57%) and MPA patients (72 vs. 45%), and higher cyclophosphamide use (50 vs. 35%; Table). eGFR increased on average 16.1 and 7.7 mL/min/1.73 m2 at Week 52 in the avacopan and prednisone groups, respectively (P=0.003). More patients in the avacopan group had an increase in eGFR of ≥2-fold (P=0.030) and above 20 mL/min/1.73 m2 (P=0.024), and a higher number of patients had increases in eGFR above 30 and 45 mL/min/1.73 m2. eGFR in one patient in the avacopan group increased to 65 at Week 52 (baseline 17). Serious adverse events occurred in 13/27 patients (48%) in the avacopan group (1 death due to bronchopneumonia) and 16/23 patients (70%) in the prednisone group (1 death due to pleural empyema).
Conclusion
In ADVOCATE eGFR improved more in the avacopan vs. control group, with greater proportional GFR recovery in those with the most severe renal involvement.
Reference: Jayne et al. NEJM 2021;384:599-609.
eGFR Results
| Avacopan (N=27) | Prednisone (N=23) | |
| Age (years), mean (SD) | 67.1 (11.13) | 64.8 (17.22) |
| Newly diagnosed / Relapsed AAV | 23 (85%) / 4 (15%) | 21 (91%) / 2 (9%) |
| Myeloperoxidase+ / Proteinase 3+ AAV Microscopic polyangiitis / Granulomatosis with polyangiitis | 22 (81%) / 5 (19%) 20 (74%) / 7 (26%) | 20 (87%) / 3 (13%) 16 (70%) / 7 (30%) |
| Rituximab / cyclophosphamide background treatment | 12 (44%) / 15 (56%) | 13 (57%) / 10 (43%) |
| Baseline eGFR (mL/min/1.73 m^2), mean (SD) | 17.6 (1.86) | 17.5 (2.04) |
| LSM change in eGFR at Week 26, mean (SEM) | 11.9 (1.85)* | 6.1 (2.00) |
| LSM change in eGFR at Week 52, mean (SEM) | 16.1 (1.88)** | 7.7 (2.01) |
| Last# eGFR ≥ 2-fold baseline eGFR, n (%) | 11 (40.7%)* | 3 (13.0%) |
| Last eGFR >20 mL/min/1.73 m^2, n (%) | 23 (85.2%)* | 13 (56.5%) |
| Last eGFR ≥ 30 mL/min/1.73 m^2, n (%) | 13 (48.1%) | 7 (30.4%) |
| Last eGFR ≥ 45 mL/min/1.73 m^2, n (%) | 6 (22.2%) | 1 (4.3%) |
| Last eGFR ≥ 60 mL/min/1.73 m^2, n (%) | 1 (3.7%) | 0 (0%) |
| Last eGFR lower than baseline, n (%) | 4 (14.8%) | 4 (17.4%) |
| Requiring dialysis during 52-week period## | 1 (3.7%) | 2 (8.7%) |
| Urinary albumin:creatinine ratio Baseline geometric mean (range) (mg/g) LSM % change from baseline to Weeks 4 / 13 / 26 / 52 | 594 (32-2830) -16%* / -35%* / -55% / -62% | 740 (56-3516) +66% / +20% / -40% / -62% |
| Total glucocorticoid dose during 52-week period, mean / median | 1094 mg / 384 mg | 3661 mg / 2920 mg |
| AAV=ANCA-associated vasculitis; eGFR=estimated glomerular filtration rate; LSM=least squares mean; SD=standard deviation; SEM=standard error of mean. * P < 0.05, ** P < 0.01 for Avacopan vs. Prednisone # Last=last eGFR measurement during the 52-week treatment period ## One patient in each group had a single dialysis session; the number of dialysis sessions in the second patient in the prednisone group is unknown. | ||
Funding
- Commercial Support – ChemoCentryx