Kidney international reports
Distinct Pharmacodynamic Complement Biomarker Signatures Define Iptacopan and Pegcetacoplan Treatment in C3 Glomerulopathy
By Zhang Y, Martín Merinero H, Carmen AR and 11 others.
Abstract
Introduction
C3 glomerulopathy (C3G) is driven by alternative pathway (AP) dysregulation. Iptacopan inhibits factor B, whereas pegcetacoplan inhibits C3/C3b, suggesting distinct pharmacodynamic (PD) biomarker profiles.
Methods
We conducted an exploratory, nonrandomized observational cohort study of patients with biopsy-confirmed C3G treated with iptacopan (n = 9) or pegcetacoplan (n = 9), using paired pretreatment and approximately 3-month posttreatment samples. Complement activity, protein levels, activation products, autoantibodies, and genetic findings were assessed. Profiles were classified as PD-concordant (PDC), largely PD-concordant (LPDC), or PD-discordant (PDD) using treatment-specific signatures.