Avacopan for anti-neutrophil cytoplasm antibodies-associated vasculitis: a multicentre real-world study

Avacopan, a selective C5aR1 inhibitor, recently emerged as a glucocorticoid (GCs) sparing agent in anti-neutrophil cytoplasm antibodies (ANCA)-associated vasculitis (AAV). We aim to evaluate the tolerance and efficacy of avacopan given outside randomized clinical trials or with severe kidney involvement.

In this multicentre retrospective study, we reviewed the clinical charts of patients with AAV and contraindication to high dose of GCs who received avacopan 30 mg b.i.d plus standard-of-care regimen owing to the French early access program between 2020 and 2023. Efficacy and safety data were recorded using a standardized case report form.

Among the 31 patients (median age 72 years), 10 had a relapsing AAV, 20 had anti-myeloperoxidase antibodies and 30 had kidney vasculitis. Induction regimen included rituximab (n = 27), cyclophosphamide (n = 2) or both (n = 2). Five patients did not receive GCs. Despite rapid GCs tapering (which were withdrawn in 23 patients before month 3), 25 patients (81%) had a favourable outcome and no severe adverse event. The estimated glomerular filtration rate increased from 19 [15; 34] to 35 mL/min/1.73 m2 [23; 45] at month 12 (P < 0.05), independently of kidney biopsies findings. One patient developed refractory AAV and two had a relapse while receiving avacopan. At month 12, ANCA remained positive in 10/18 patients (55.5%). Two patients developed severe adverse events leading to a withdrawal of avacopan (hepatitis and age-related macular degeneration).

The GCs' sparing effect of avacopan was confirmed, even in patients with severe kidney vasculitis, but further studies are required to identify the optimal dosing of GCs when avacopan is used.