A Pharmacovigilance Study of Immune Checkpoint Inhibitor-Associated Cholangitis: Insights From the FDA Adverse Event Reporting System.

[AIM] 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. The aim was 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 cholangitis following ICI treatment was assessed.

[RESULTS] A total of 1102 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%). 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 and 95% confidence interval [CI]: 22.84-26.59), followed by programmed death-ligand 1 inhibitors (ROR = 19.03 and 95% CI: 16.41-22.08). In contrast, cytotoxic T-lymphocyte-associated protein 4 inhibitors showed no significant association (ROR = 2.08 and 95% CI: 0.93-4.64). The median TTO was 77 days (interquartile range: 31-164 days).

[CONCLUSION] From a pharmacovigilance perspective, this study characterizes certain clinical features of ICI-associated cholangitis, elucidates distinct risk profiles across ICI classes, and emphasized the importance of constant monitoring. However, further studies remain essential to fully understand this rare irAE.