Dr ANNA POSTEMA1, DR KEN CHAU1,2, DR ZIHAO TAN3, DR PAUL KUBLER4, PROF DWARAKANATHAN RANGANATHAN1, DR MADHIVANAN SUNDARAM1, DR DHARMENAAN PALAMUTHUSINGAM1, Dr EOIN O' SULLIVAN1,5,6, DR SHAUN CHANDLER1
1Kidney Health Service, Metro North Hospital and Health Service, Brisbane, Australia, 2School of Medicine and Dentistry, Griffith University, Brisbane, Australia, 3Department of Immunology, Royal Brisbane and Womens Hospital, Brisbane, Australia, 4Department of Rheumatology, Royal Brisbane and Womens Hospital, Brisbane, Australia, 5QIMR Berghofer Medical Research Institute, Brisbane, Australia, 6Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia
Biography:
Dr. Shaun Chandler is a Consultant Nephrologist based in Brisbane, Australia, affiliated with the Metro North Kidney Health Service. He also holds academic positions as a Senior Lecturer at both the University of Queensland and Griffith University. Dr. Chandler's clinical and research interests encompass a broad spectrum of nephrology, including kidney transplantation, complement disorders, dialysis and glomerular disease.
Aim:
To describe early Australian experience with avacopan in the management of ANCA-associated vasculitis (AAV), focusing on safety signals, drug interactions, and monitoring requirements.
Background:
Avacopan is an oral C5a receptor inhibitor approved for AAV, with potential to reduce glucocorticoid exposure and related toxicity. However, real-world post-marketing data, especially regarding adverse effects and drug interactions, are still emerging.
Methods:
We retrospectively reviewed five consecutive patients initiated on avacopan at a tertiary Australian centre since PBS listing of avacopan in Oct 2024. Clinical indications, adverse events, and treatment outcomes were assessed through medical record review.
Results:
Steroid minimisation was the primary indication across all cases, driven by comorbidities including osteoporosis, metabolic syndrome, limited scleroderma, and infection risk. By three months following initiation, three patients remained on avacopan, of which two achieved biochemical remission. Discontinuations were related to liver enzyme derangement (n=1) and marked eosinophilia (n=1). One patient developed hepatotoxicity whilst concurrently on fluconazole, raising concern for CYP3A4-mediated interactions even with relatively weak inhibitors, underscoring the need for caution during coadministration. Drug interactions, particularly with azole antifungals, pose a significant challenge to avacopan use. Hepatotoxicity remains a key concern due to post-marketing reports including vanishing bile duct syndrome, although imaging findings were negative in this case. A second patient developed significant eosinophilia, which resolved following withdrawal of avacopan. Weekly liver function tests and white cell count monitoring enabled early detection of these complications.
Conclusions:
This early experience with avacopan highlights important safety considerations, including vigilance for hepatotoxicity, eosinophilia, and drug interactions. Proactive monitoring and multidisciplinary management are critical for optimising patient outcomes. Staggered introduction of medications associated with liver injury may mitigate risk and isolate culprit agents.