S88 Immune Checkpoint-Inhibitors Are Associated With a Higher Risk of Cholangitis: A Nationwide Population-Wide Study

Abstract

Introduction: Immune checkpoint-inhibitors (ICIs) improve the survival in certain cancers. However, side effects of ICIs might limit its use. Little is known about their biliary toxicity. Accordingly, we used a large database to investigate the epidemiology of ICI-induced cholangitis and describe underlying associations. Methods: A multi-institutional database (Explorys Inc, Cleveland, OH, USA), an aggregate of electronic health record data from 26 US healthcare systems was surveyed. A cohort of patients who were on ICIs (nivolumab, pembrolizumab, ipilimumab and atezolizumab) between 2011 and 2022 was identified. Subsequently, patients who developed new Systematized Nomenclature of Medicine-Clinical Terms diagnosis of cholangitis after taking ICIs were selected. The prevalence of ICI-induced cholangitis as calculated, and underlying associations were described. Results: There were 70,398,640 in the database of which 417,390 patients had a diagnosis of cholangitis. Among these patients, 260 patients had a prior history of ICI use. Compared to patients with history of ICI use who didn’t develop cholangitis (n=19,940), patients with ICI and cholangitis were more likely to be female [OR: 1.38; 95% CI 1.08–1.76]. There were no statistically significant age or race-based differences. Overall, patients who received any ICI had a significantly higher risk of cholangitis compared to the general population [OR: 1.28; 95% CI 1.13–1.45]. Patients who received Ipilimumab had the highest odds of developing ICI-induced cholangitis (Figure). Conclusion: In this large retrospective study, we found that patients taking ICI have a higher risk of cholangitis compared to the general population. Ipilimumab poses the greatest risk for ICI-induced for cholangitis. The risk of cholangitis should be discussed with all patients prior to initiating an ICI, as it may be a factor in choosing among ICIs.Figure 1.: Odds Ratio with 95% Confidence Interval of Immune Checkpoint Inhibitor-Induced Cholangitis Table 1. - Baseline Characteristics of Patients Receiving ICIs Variable Patients who received ICI Patients with Cholangitis who did not receive ICI ICI without Cholangitis ICI-Induced Cholangitis Age18 -65>65 7190 (37%)12,250 (63%) 90 (35%)160 (62%) 417,140 (59%)288,960 (41%) Female 8,130 (42%) 130 (50%) 475,350 (67%) RaceCaucasianOthers 16,150 (84%)3180 (16%) 220 (85%)40 (15%) Co-morbiditiesHypertensionT2DMHyperlipidemiaObesityCADCholedocholithiasis 19,330 (71%)5,560 (29%)11,830 (62%)4,510 (23%)5,720 (30%)1,570 (8%) 200 (77%)90 (35%)160 (62%)90 (35%)90 (35%)170 (65%) 382,890 (54%)176,910 (25%)329,520 (47%)236,120 (33%)130,060 (18%)532,590 (75%)