A pharmacovigilance study of immune checkpoint inhibitor-associated cholangitis using the Food and Drug Administration adverse event reporting system

Background Immune checkpoint inhibitor (ICI)-associated cholangitis is a rare immune-related adverse event (irAE). However, large-scale clinical studies specifically investigating this toxicity are still lacking. This study aimed to describe ICI-associated cholangitis reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Methods Reports of irAEs were extracted from the FAERS database (Q1 2011 to Q4 2024). Cases of ICI-associated cholangitis were identified using the following Preferred Terms from the Medical Dictionary for Regulatory Activities (version 27.1): “cholangitis”, “sclerosing cholangitis”, and “immune-mediated cholangitis”. Reporting odds ratio (ROR) method was performed to evaluate the association between cholangitis and different ICI therapies. Additionally, the clinical features of ICI-associated cholangitis were characterized, and the time-to-onset (TTO) of ICI-associated cholangitis was assessed. Results A total of 1,102 patients with ICI-associated cholangitis were identified. Male patients (n = 628, 56.99%) outnumbered females (n = 334, 30.31%). Most patients were aged ≥ 65 years (n = 540, 49.00%) and from Japan (n = 817, 74.14%). Hospitalization (n = 454, 41.20%) was the most frequent clinical outcome. Programmed cell death protein 1 inhibitors showed the strongest risk association (ROR = 24.65, 95% confidence interval [CI]: 22.84–26.59), followed by programmed death-ligand 1 inhibitors (ROR = 19.03, 95% CI: 16.41–22.08). In contrast, cytotoxic T-lymphocyte-associated protein 4 inhibitors demonstrated no significant association (ROR = 2.08, 95% CI: 0.93–4.64). The median TTO was 77 days (interquartile range: 31–164 days). Conclusion ICI-associated cholangitis represents a rare but clinically significant irAE. This study elucidates distinct risk profiles across ICI classes and characterizes the clinical features of this toxicity, providing unique insights to inform clinical management.