Hepatotoxic adverse events with immune checkpoint inhibitors: Real world pharmacovigilance study using FAERS database.

2602 Background: Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment. With their increasing use, it is important to track and manage potential adverse events (AEs) . One such AE of ICI therapy is immune-mediated liver injury (ILICI). We aim to review the real-world data on ILICI using FDA Adverse Event Reporting System (FAERS) database. Methods: We queried FAERS using a search-by-product strategy on 22nd January 2025 and retrieved 224889 adverse events from 2013-2024. We employed 5 ICIs in the analysis (Pembrolizumab, Nivolumab, Atezolizumab, Durvalumab, and Ipilimumab). Descriptive statistics were carried out, and disproportionality analysis was done by calculating the reportable odds ratio (ROR) with 95% confidence intervals (CI). ROR was considered significant when the lower limit of the 95% CI was > 1. RORs were calculated for all hepatic events in general and Autoimmune Hepatitis (AIH), Drug-induced liver injury (DILI), Vanishing bile duct syndrome (VBDS), Primary biliary cholangitis (PBC), and Venooccluisve disease (VOD). Results: Total AEs from all included ICIs were 224889 and Hepatobiliary AEs constitute 9.2% of all AEs across all ICIs. ROR for any hepatic event is highest with Durvalumab i.e., 17.97 (16.08,20.08) in general as compared to the rest of the ICIs. AIH was seen highest with Ipilimumab with a ROR of 48.0 (43.1, 53.5); DILI with Pembrolizumab with a ROR of 5.8 (5.3, 6.4) (Overlapping CI); VBDS and PBC with Pembrolizumab with a ROR of 7.93 (4.9, 12.8) and 7.91 (4.46,14.03) respectively. Atezolizumab showed the highest ROR of 6.15 (3.6, 10.4) for VOD . (Table) Conclusions: This is the largest real-world study demonstrating specific hepatotoxic AEs with ICIs. Our results show varying patterns of hepatotoxicity with ICIs. Knowing these patterns will help us make better decisions in treating patients with ICIs. Baseline characteristics, hepatic AEs and outcomes. Baseline characteristic Pembrolizumab(n= 67603) Nivolumab(n=79283) Atezolizumab(n=28521) Durvalumab (n=13303) Ipilimumab (n= 36179) ROR for any hepatic event (95% CI) 8.24 (7.66,8.87) 7.46 (6.95, 8.01) 7.94 (7.08, 8.89) 17.97 (16.08, 20.08) 11.47 (10.54, 12.48) ROR for AIH 21.34 (18.9, 24.0) 27.3 (24.8, 30.1) 22.3 (18.7, 26.5) 22.3 (18.7, 26.5) 48.0 (43.1, 53.5) ROR for DILI 5.8 (5.3, 6.4) 3.74 (3.34, 4.19) 5.3 (4.61,6.29) 5.3 (4.61, 6.29) 5.04 (4.37, 5.82) ROR for VBDS 7.93 (4.9, 12.8) 4.37 (2.41, 7.94) 0.5 (0.03, 8.8) 1.1 (0.15, 7.86) 2.61 (0.84, 8.1) ROR for VOD 2.22 (1.2, 3.9) 3.79 (2.5, 5.6) 6.15 (3.6, 10.4) 0.44 (0.06, 3.12) 2.08 (0.9, 4.63) ROR for PBC 7.91 (4.46,14.03) 3.37 (1.5, 7.5) 0.78 (0.04, 12.5) 1.51 (0.21, 11.1) 2.46 (0.6, 9.8) Hepatic AEs included in the ROR calculation with these agents are Drug-Induced Liver Injury (DILI), Autoimmune hepatitis (AIH), Vanishing bile duct syndrome (VBDS), Veno-occlusive disease (VOD), Primary biliary cholangitis (PBC).