Medicine Advances · Published 2026-03-01 · DOI 10.1002/med4.70056
ABSTRACT Background Avacopan has been approved for the treatment of severe active the antineutrophil cytoplasmic antibody‐associated vasculitis in adults. However, it has not been subjected to post‐marketing surveillance to assess real‐world adverse reactions (AEs). This study aims to identify potential AEs of avacopan through disproportionality analysis. Methods Using post‐marketing AE data for avacopan obtained from the Food and Drug Administration's Adverse Event Reporting System, we conducted a disproportionality analysis to identify positive and novel signals at the preferred term level. Additionally, our analysis included assessment of time‐to‐onset, Weibull shape parameter, cumulative incidence, clinical priority, and subgroup analysis. Finally, we employed network pharmacology to elucidate the underlying biological mechanisms of avacopan‐associated hepatotoxicity. Results We included a total of 1020 patients and identified 19 positive preferred terms, 11 of which were novel. The median time‐to‐onset for AEs was 55.5 days. The Weibull shape parameter for the entire cohort indicated an early failure type. Subgroup analysis revealed the relative risks associated with specific AEs. Furthermore, through network pharmacology, we predicted a total of 71 potential targets associated with liver injury and identified 54 core target genes. The phosphoinositide 3‐kinase (PI3K)‐protein kinase B (Akt) signaling pathway was determined to be associated with avacopan‐induced hepatotoxicity. Conclusions Hepatotoxicity is a frequently reported AE. The PI3K/Akt pathway is a potential target for mitigating avacopan‐associated hepatotoxicity. Further studies are urgently needed to explore a possible causal relationship between avacopan and vanishing bile duct syndrome.
Abstract from DOAJ. Public domain (CC0 1.0).
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