(P-468) Biliary Toxicity of Immune Checkpoint Inhibitors: A Pharmacovigilance Study Through FDA Adverse Event Reporting System Database

Background: Immune checkpoint inhibitors (ICIs) have demonstrated remarkable clinical benefits in cancer treatment. However, they are associated with a unique spectrum of immune-related adverse events (irAEs). The association and clinical features of ICI-mediated biliary toxicities are not well characterized.

Objectives: We aim to conduct a pharmacovigilance study to characterize ICI-mediated biliary toxicities using the US Food and Drug Administration Adverse Events Reporting System (FAERS), and to further analyze the potential biliary toxicities associated with different ICIs.

Methods: We performed disproportionality analysis to assess the association between biliary adverse events (AEs) and ICIs in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from the third quarter of 2010 to first quarter of 2020. We evaluated the association between ICIs and biliary AEs using reporting odds ratios (ROR) and information component (IC).

Results: 906 reports related to ICI-mediated biliary AEs were identified in the database. The mean age of affected patients was 64.8±12.1 years, the AEs occurred more in men than women (60.1% vs 39.9%), and were most commonly reported from patients with thoracic tumors (39.5%). Comparing with other therapies used to treat cancer, ICI agents were associated with increased reporting of biliary AEs (ROR 1.82, 95%CI 1.69-1.95; IC0250.78), particularly cholangitis (ROR 5.52, 95%CI 4.94-6.17; IC0251.93), biliary tract infection (ROR 5.58, 95% CI 3.91-7.96; IC0251.54). PD-1 inhibitors, nivolumab (ROR 18.76, 95% CI 13.81-25.48; IC0253.13) and pembrolizumab (ROR 24.56, 95% CI 17.69-34.10; IC025 3.46), showed strong signals in sclerosing cholangitis; anti-CTLA-4 therapy (ipilimumab) had no association with any biliary AEs

Conclusions: ICIs showed a spectrum of distinct classes of biliary AEs that maybe life-threatening. Clinicians should recognize the presentation of these irAEs and differentiate it from cases of traditional immune-mediated hepatotoxicity.