Kidney Week Educational Symposia-Emerging Therapies for ANCA-Associated Vasculitis

Video Transcription

Video Summary

The session introduces “Emerging Therapies for ANCA-Associated Vasculitis,” emphasizing recent progress implicating the complement system as a therapeutic target. ANCA vasculitis is an autoimmune small-vessel vasculitis with frequent renal involvement, typically pauci-immune necrotizing crescentic glomerulonephritis. Current therapies (cyclophosphamide/rituximab plus glucocorticoids) are effective but nonspecific, toxic, and complicated by relapse and infection risk, motivating pathogenesis-based approaches.<br /><br />Background evidence supporting complement involvement is reviewed: kidney biopsies in ~50% of patients show immunoglobulin and complement deposition (challenging the “pure pauci-immune” concept). Mouse models demonstrated a key role for the alternative pathway and especially C5a–C5a receptor (C5aR) signaling in neutrophil activation and tissue injury. C5aR-deficient and pharmacologic blockade models showed protection from ANCA glomerulonephritis, leading to clinical translation with C5aR inhibition (avacopan).<br /><br />Prof. Bar-Gemmer summarizes human renal-tissue studies assessing complement components (immunofluorescence, EM, mass spectrometry, transcriptomics). Findings are heterogeneous: C3 deposits appear in about half of biopsies; pathway attribution varies (alternative vs possible classical contributions), serum complement levels often do not reflect tissue activation, and C3 positivity may associate with worse renal/survival outcomes. She calls for larger standardized biopsy cohorts linking complement “phenotypes” to histology, clinical course, and treatment response.<br /><br />Prof. Jones reviews treatment: induction with rituximab or cyclophosphamide (plus steroids), selective use of plasma exchange for highest ESKD risk, maintenance often with rituximab (but limited by hypogammaglobulinemia/infections), and steroid minimization (PEXIVAS reduced-dose regimen). Complement targeting addresses unmet need for steroid-sparing therapy. CLEAR/CLASSIC supported safety and suggested renal benefits; the phase 3 ADVOCATE trial showed avacopan was noninferior to prednisone for remission at 26 weeks, superior for sustained remission at 52 weeks, improved quality of life, reduced steroid toxicity, and improved eGFR recovery. Q&A covers plasma exchange selection, interpretation of low-positive PR3 without biopsy vasculitis, pulmonary hemorrhage evidence gaps, and trial design considerations.

Asset Subtitle

Moderators: Ulf Panzer

Introduction - Ulf Panzer
Pathogenesis and Diagnostic Approaches to ANCA Vasculitis - Ingeborg Bajema
Updates on the Treatment of ANCA Vasculitis - Rachel Jones

Support is provided by an educational grant from ChemoCentryx, Inc.

Meta Tag

Date 11/5/2022

Pathway 1 Glomerular Diseases

Pathway 2

Session ID 438084

Session Type ES - Educational Symposium

Keywords

ANCA-associated vasculitis

pauci-immune necrotizing crescentic glomerulonephritis

complement system

alternative complement pathway

C5a–C5a receptor (C5aR) signaling

avacopan

rituximab

cyclophosphamide

glucocorticoid-sparing therapy

ADVOCATE trial