Avacopan for the Treatment of ANCA-Associated Vasculitis
In the phase 3 ADVOCATE trial, avacopan was non-inferior at week 26 and superior at week 52 for sustained remission in ANCA-associated vasculitis, with improved renal recovery and markedly reduced glucocorticoid exposure compared with a prednisone taper.
Background
ANCA-associated vasculitis frequently involves the kidneys and is conventionally treated with high-dose, prolonged glucocorticoids that carry substantial toxicity. Avacopan, an oral complement C5a receptor inhibitor, was developed to allow effective disease control while sparing glucocorticoids.
Study design
ADVOCATE was a 330-patient phase 3 trial comparing avacopan with a standard prednisone taper, both on a background of induction therapy with rituximab or cyclophosphamide; about 81% of patients had renal involvement. Key efficacy outcomes were remission at week 26 and sustained remission at week 52, with additional assessment of glucocorticoid toxicity, eGFR, and albuminuria.
Key findings
In the rituximab subgroup, remission at week 26 was similar between arms (77.6% avacopan vs 75.7% prednisone taper), while sustained remission at week 52 favoured avacopan (71.0% vs 56.1%). eGFR increased on average 7.3 mL/min/1.73 m2 with avacopan versus 4.1 with prednisone at week 52, and among patients with baseline eGFR of 20 or below, eGFR rose 16.1 versus 7.7 mL/min/1.73 m2. Relapse rate, speed of albuminuria reduction, and glucocorticoid toxicity all favoured avacopan, with serious adverse events comparable between groups.
Clinical implications
Avacopan provided durable remission with better renal recovery and substantially lower glucocorticoid burden, supporting it as a glucocorticoid-sparing option in ANCA-associated vasculitis, including patients with severe renal insufficiency at presentation.
Category
Research
Source
N Engl J Med
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