Abstract: FR-PO0888
Changes in Urinary sCD163 and Plasma Endotrophin Levels in Response to Treatment with Avacopan for Granulomatosis with Polyangiitis (GPA) and Microscopic Polyangiitis (MPA) with Kidney Involvement
Session Information
- Glomerular Outcomes: From Proteinuria to Prognosis
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Almaani, Salem, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Song, Christina, Amgen Inc, Thousand Oaks, California, United States
- Bozeman, Alana, Amgen Inc, Thousand Oaks, California, United States
- Gulati, Jyotsna, Amgen Inc, Thousand Oaks, California, United States
- Jayne, David R.W., University of Cambridge, Cambridge, England, United Kingdom
- Merkel, Peter A., University of Pennsylvania, Philadelphia, Pennsylvania, United States
- Geetha, Duvuru, Johns Hopkins University, Baltimore, Maryland, United States
- Little, Mark Alan, Trinity College Dublin Trinity Translational Medicine Institute, Dublin, Leinster, Ireland
Group or Team Name
- ADVOCATE Study Group.
Background
For patients with kidney disease due to GPA/MPA in the Phase 3 ADVOCATE trial, those in the avacopan arm had greater improvement in eGFR at week (W) 52 and faster reduction in albuminuria than those in the prednisone taper arm. Further biomarker analysis, including markers of kidney inflammation and fibrosis, may help elucidate mechanisms underlying differential kidney response to treatment.
Methods
In ADVOCATE, 268 (81%) of 330 patients had kidney involvement at baseline and were randomized to receive a prednisone taper (n=134) or avacopan regimen (n=134) with allowances for glucocorticoids (GC) in both arms. Urinary soluble CD163, a marker of macrophage activation, was measured by Luminex assay and normalized to urinary creatinine as a ratio (UsCD163/Cr), and plasma endotrophin, a marker of inflammation and fibrosis, was measured by PRO-C6 ELISA.
Results
Baseline UsCD163/Cr and plasma endotrophin levels were higher in patients with lower baseline eGFR (p<0.01 for both; Figure 1). Although there was a suggested faster decline at W4 in UsCD163/Cr in the avacopan vs prednisone taper arm in patients with eGFR <30 mL/min/1.73m2 (Figure 1A), percent change from baseline was not significantly different. Across all eGFR categories, plasma endotrophin was highest at W4 in the avacopan arm followed by a progressive decline; the prednisone taper arm showed an initial decrease at W4 followed by an increase with highest levels at W26 and a decline at W52 (interaction p<0.01 at W4 for all groups and W26 for eGFR <30; Figure 1B).
Conclusion
This secondary analysis suggests that avacopan and prednisone taper regimens affect macrophage activation, yet exhibit marked early differences in plasma endotrophin levels. Early differences could indicate that an avacopan regimen with earlier GC discontinuation may have divergent effects on fibrotic remodeling, potentially influencing clinical outcomes that need to be explored.
Funding
- Commercial Support – This study was funded by Amgen Inc. Writing and editorial support was funded by Amgen Inc. and provided by Rachel Gurlin, PhD, of Amgen Inc. and Rebecca Lane, PhD, of Peloton Advantage, LLC, an OPEN Health company.