The safety profiles of avacopan on microscopic polyangiitis and granulomatosis with polyangiitis: A real-world pharmacovigilance analysis

Yang Li^1,2Anna Meng^1,2Yue Wang^2*

• ¹Department of pharmacy,Nanjing First Hospital,NanJing Medical University, Nanjing, China
• ²Nanjing First Hospital, Nanjing, China

Background Avacopan is an oral selective C5a receptor inhibitor. It received FDA approval in October 2021 for use with standard glucocorticoid therapy to treat antineutrophil cytoplasmic antibody-associated vasculitis. However, there are limitations to understanding adverse events (AEs) in clinical practice. In this study, we analyzed AEs related to avacopan by mining the FDA Adverse Event Reporting System (FAERS). Methods Adverse event reports associated with avacopan were retrieved from the FAERS database covering Q1 2022 to Q4 2024. After data standardization, reports exclusively involving avacopan were retained. Two disproportionality analysis methods, namely the reporting odds ratio and Bayesian confidence propagation neural network, were utilized to detect safety signals related to avacopan. A semi-quantitative scoring approach was employed to evaluate the clinical priority of the detected signals. Moreover, racial disparities in the occurrence risks of critical adverse event signals as well as temporal patterns of avacopan-related AEs were examined. Results Among 1,128 avacopan-related reports, 33 adverse event signals were identified. These included label-listed AEs (nausea, fatigue, diarrhea, headache, rash, hypertension, blood creatinine increased, and abnormal liver function). Five new potential AEs were detected, including alopecia, increased appetite, hyperaesthesia teeth, oesophageal disorder, and muscle atrophy. Clinically, 0 were classified as high-priority signals, 2 as moderate-priority signals, and 31 as low-priority signals. Compared to American patients, Japanese patients exhibited a higher risk of liver dysfunction (p<0.001), while alopecia occurred exclusively in the American patient population. The median time to AE onset time for avacopan was 86.5 days(interquartile range [IQR] 27-236.75), with most occurring within the first month of treatment. Conclusions Avacopan exhibits favorable real-world safety with no high-priority AEs identified. Our findings may provide important evidence for future clinical research and the management of safety issues related to avacopan.