Hepatobiliary Adverse Events Associated With Avacopan: Analysis of the JADER Database

BACKGROUND/AIM: Avacopan, a selective C5a receptor antagonist approved for anti-neutrophil cytoplasmic antibody-associated vasculitis, has been associated with hepatobiliary disorders including vanishing bile duct syndrome (VBDS). These events have been reported more frequently in Japanese patients than in Western populations. To address this population-specific safety concern, we characterized the reporting patterns of avacopan-associated hepatobiliary disorders using the Japanese Adverse Drug Event Report (JADER) database. PATIENTS AND METHODS: We analyzed reports submitted to JADER between April 2004 and January 2026 in which avacopan was registered as a suspect drug. Hepatobiliary adverse events were defined as a composite set comprising preferred terms (PTs) under the System Organ Class (SOC) "Hepatobiliary disorders" (code 10019805) of Medical Dictionary for Regulatory Activities (MedDRA)/J version 29.0 and two liver-related PTs classified under the SOC "Investigations" (code 10022891): Liver function test increased (10077692) and hepatic enzymes increased (10060795). Disproportionality was assessed using the reporting odds ratio with 95% confidence intervals (CIs); a signal was defined as three or more reports with a lower CI limit exceeding 1.0. Time to onset was calculated from treatment start to hepatobiliary adverse events onset, and post-event outcomes were categorized based on available JADER outcome data. RESULTS: Among 685 avacopan-related reports, disproportionality signals were detected for all hepatobiliary adverse events evaluated. The median time to onset of hepatobiliary adverse events ranged from 33 to 56.5 days, with most events occurring within one to two months after avacopan treatment. Of 226 reports with outcome data, 19 (8.4%) recorded death. Notably, 13 of 27 VBDS reports (48.1%) recorded death as the outcome, a markedly higher proportion than that for other hepatobiliary adverse events. CONCLUSION: These findings support the importance of continued post-marketing surveillance and monitoring of hepatobiliary events during avacopan treatment.