Infection-related and Hepatobiliary Death Outcome Reports Involving Avacopan in the Japanese Pharmacovigilance Database.

BACKGROUND/AIM: Avacopan is used to treat antineutrophil cytoplasmic antibody-associated vasculitis. In Japan, serious hepatobiliary adverse events, including vanishing bile duct syndrome, have recently become a major safety concern. This study characterized reports with death recorded as the outcome involving avacopan in the Japanese Adverse Drug Event Report database (JADER). PATIENTS AND METHODS: Reports involving avacopan as a suspected drug and death recorded as the outcome were extracted from JADER. Adverse events were classified by primary system organ class and preferred term. Quarterly reporting trends and time-to-onset were evaluated for hepatobiliary and infection-related adverse events. RESULTS: A total of 79 reports were identified; 64 involved patients aged ≥70 years. Infections and infestations were the most frequent system organ classes among adverse events with death recorded as the outcome (n=46), followed by hepatobiliary disorders (n=21). Vanishing bile duct syndrome was the most frequent hepatobiliary preferred term (n=13). Pneumocystis jirovecii pneumonia and pneumonia were the most frequent infection-related preferred terms (n=9 each). Median time-to-onset was 49 days for hepatobiliary disorders and 75 days for infections and infestations. The proportions of events occurring within 90 days were 94.1% for hepatobiliary disorders and 57.1% for infections and infestations. CONCLUSION: In JADER, death outcome reports involving avacopan frequently included infection-related and hepatobiliary events. Hepatobiliary events occurred mainly within 90 days, whereas infection-related events showed a broader time-to-onset distribution. These findings suggest the need for early hepatobiliary monitoring and continued attention to serious infections during avacopan treatment.