Understanding the Mechanisms of Action of Emerging B-Cell Modulators in IgAN

In this segment, the panel compares different disease-modifying therapeutic strategies under investigation for IgA nephropathy. They outline how BAFF/APRIL-targeting agents aim to reduce production of galactose-deficient IgA1 by modulating B-cell maturation and plasma cell survival, mentioning emerging agents such as atacicept, povetacicept, and sibeprenlimab. They contrast this upstream approach with interventions that act downstream, including complement pathway inhibitors that target the alternative or lectin pathway to reduce inflammatory injury after immune complex deposition. The group notes that targeted-release budesonide sits between these mechanisms—modulating mucosal immunity without broad systemic suppression. The panel emphasizes that therapy selection will likely depend on disease severity, proteinuria response to supportive care, and patient tolerance. They also address real-world considerations: frequent monitoring early in therapy, interpreting the trajectory of proteinuria and eGFR, and educating patients on expected timelines of response. Overall, the discussion highlights movement toward precision, mechanism-directed therapy.