Integrated pharmacovigilance assessment of drug-associated cholangitis: signal detection, clinical characterization, and mechanistic insights.

BACKGROUND: Drug-related cholangitis has been increasingly recognized in clinical practice; however, the spectrum of implicated agents and their relative contributions remain incompletely characterized. OBJECTIVE: To systematically identify drugs associated with cholangitis reporting and to characterize disproportionality signals and time-to-onset patterns using a large pharmacovigilance database. METHODS: Data were extracted from the FDA Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the second quarter of 2025. Disproportionality analysis was performed using reporting odds ratios (RORs) with 95% confidence intervals (CIs). Significant signals were defined as ROR >1, with the lower bound of the 95% CI > 1, and a Bonferroni correction was applied for multiple comparisons. A case/non-case design was used for regression analyses. Candidate drugs were selected using the least absolute shrinkage and selection operator (LASSO) regression and further evaluated in a multivariable logistic regression model. Time-to-onset was assessed using descriptive statistics and visualized using distribution plots. RESULTS: A total of 17,083 reports of drug-related cholangitis were identified. Eighty-four drugs showed significant disproportionality signals, predominantly involving antineoplastic agents, immunomodulators, and antidiabetic drugs. Multivariable analysis identified older age, female sex, and 21 drugs as factors associated with increased reporting odds of cholangitis reporting within the FAERS database. These findings should be interpreted as pharmacovigilance signals intended for hypothesis generation rather than confirmation of causal relationships. The median time to onset was 97 days (interquartile range [IQR], 7-102 days), with most cases occurring within the first 3 months after treatment initiation. CONCLUSION: This large-scale pharmacovigilance study identified multiple drug classes associated with increased reporting odds of cholangitis and demonstrated an early-onset pattern. These findings highlight the importance of clinical vigilance during the initial treatment period and provide a basis for future mechanistic and epidemiological studies.