What is the evidence for using Tavneos (avacopan) in patients with End-Stage Renal Disease (ESRD) and pauci-immune glomerulonephritis, particularly those with ANCA-associated vasculitis?

Tavneos (Avacopan) for ESRD Patients with Pauci-Immune Glomerulonephritis

Direct Answer

Tavneos (avacopan) can be used in ESRD patients with ANCA-associated vasculitis, including those requiring dialysis, as the ADVOCATE trial specifically included dialysis-dependent patients and post-hoc analysis showed particular benefit in patients with severe renal impairment (GFR <30 ml/min/1.73 m²). 1

Evidence for Use in ESRD Population

Trial Inclusion of Dialysis Patients

• The pivotal ADVOCATE trial (N=331) that led to FDA approval explicitly enrolled patients requiring dialysis at baseline, demonstrating that avacopan is safe and effective even in the most severe renal presentations 2, 3
• The trial achieved sustained remission at 52 weeks in 65.7% of avacopan-treated patients versus 54.9% with prednisone (p=0.007 for superiority), with similar safety profiles between groups 2, 4, 3

Enhanced Benefit in Severe Renal Disease

• Post-hoc analysis specifically demonstrated greater GFR recovery with avacopan compared to glucocorticoids in patients with baseline GFR <30 ml/min/1.73 m², making it particularly advantageous for ESRD or near-ESRD patients 1, 5
• Patients with active glomerulonephritis at baseline showed superior kidney function recovery with avacopan versus prednisone, which is directly relevant to the ESRD population 1, 5

Practical Treatment Algorithm for ESRD Patients

When to Prioritize Avacopan

Use avacopan preferentially in ESRD patients with:

• Active glomerulonephritis with rapidly deteriorating kidney function 5
• Dialysis-dependent status or serum creatinine >3.4 mg/dl (>300 μmol/L) 1
• High risk for glucocorticoid complications (diabetes, osteoporosis, psychiatric disorders, obesity) 1, 5
• Potential for renal recovery (not yet chronically scarred kidneys) 5

Dosing and Administration

• Administer avacopan 30 mg orally twice daily for 52 weeks 2, 3
• Combine with standard immunosuppression: rituximab (preferred) or cyclophosphamide followed by azathioprine 2, 3
• Avacopan replaces high-dose prednisone but does not eliminate need for pulse methylprednisolone (1-3 g cumulative) in severely active disease 1

Critical Considerations for ESRD Context

Extrarenal Disease Management

• Even patients on kidney replacement therapy can experience extrarenal AAV relapses, so remission must be consolidated with maintenance therapy 1
• In patients with kidney failure, anti-MPO positivity, and no extrarenal symptoms, long-term maintenance may not be necessary and should be assessed individually 1

Guideline Positioning

• Both KDIGO 2024 and EULAR 2022 position avacopan as a "practice point" rather than formal recommendation due to moderate certainty of evidence, but this reflects overall population data—not a contraindication in ESRD 1, 5
• The evidence quality for sustained remission and severe adverse events was graded as moderate, with low certainty only for infections and discontinuation rates 1

Safety Profile in Advanced Renal Disease

• Serious adverse events occurred in 37.3% with avacopan versus 39.0% with prednisone, demonstrating comparable safety even in this high-risk population 2, 3
• Avacopan reduced cumulative glucocorticoid exposure by 2.3 g over one year and decreased glucocorticoid toxicity measured by the Glucocorticoid Toxicity Index 1, 5
• No increased risk of infections compared to standard prednisone therapy 5, 3

Adjunctive Therapies in ESRD

Plasma Exchange Consideration

• Consider plasma exchange in ESRD patients with serum creatinine >3.4 mg/dl (>300 μmol/L), especially if oliguric, or those requiring dialysis with rapidly increasing creatinine 1
• Plasma exchange reduces progression to kidney failure at 12 months but increases risk of serious infections (RR 1.19) 1
• The benefit-risk ratio favors plasma exchange most strongly in patients at highest risk of permanent ESRD 6

Common Pitfalls to Avoid

• Do not withhold avacopan based solely on ESRD status—the trial data and post-hoc analyses support its use in this population 1, 5
• Do not assume avacopan eliminates all glucocorticoid use—pulse methylprednisolone may still be needed for severely active disease with GFR <50 ml/min/1.73 m² 1
• Do not continue avacopan beyond 52 weeks without additional evidence—safety and efficacy data beyond one year are not yet available 1, 2, 3
• Do not forget maintenance therapy—even dialysis-dependent patients require consolidation with rituximab or azathioprine to prevent extrarenal relapses 1