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Abstract: FR-PO651

Renal Recovery for Patients With Baseline eGFR ≤20 in Avacopan ADVOCATE Trial

Session Information

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 AAV23 (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 treatment12 (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 / median1094 mg / 384 mg3661 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