A0541 - Early Use of Tocilizumab as an Effective Steroid-Sparing Strategy for the Treatment of Immune Checkpoint Inhibitor-Mediated Cholangiopathy: Building Foundations for Personalized Management

Introduction: Immune-mediated cholangiopathy (IMCp) is an increasingly recognized complication of immune checkpoint inhibitor therapy, often associated with exposure to anti-PD-1/L1 agents. Both intra- and extrahepatic manifestations can occur. Potential sequelae include biliary strictures and acute cholangitis. The management of IMCp remains undefined across multiple society guidelines, but published cases have offered insight into formulating effective treatment strategies. We present a complex case of a patient with IMCp successfully treated with budesonide and early tocilizumab, an IL-6 receptor antagonist.

Case Description/Methods: A 70-year-old man with a history of urothelial carcinoma (treated with neoadjuvant carboplatin/gemcitabine, followed by 3 cycles of an anti-PD-1 agent, pembrolizumab), pre-diabetes, and no underlying liver disease, presented with abnormal liver enzymes. ERCP revealed some biliary sludge but no biliary stricture. Endoscopic ultrasound 3 months later was normal. ALT normalized, but alkaline phosphatase (ALP) remained elevated; both then increased to CTCAE grade 2. R factor was 0.5. Elective cholecystectomy was attempted but aborted: He had a firm, contracted gallbladder with dilated extrahepatic biliary ducts, and the surgeon could not demarcate borders of the cystic and common bile ducts. MRCP showed intrahepatic biliary ductal dilation, ductal thickening and enhancement, and CBD dilation with a new stricture. Liver biopsy showed cholestatic hepatitis with portal and lobular inflammation and hepatocyte necrosis. A diagnosis of immune-mediated cholangiohepatitis with IMCp was made. Oral budesonide/azathioprine/ursodiol were prescribed. Five days later, subcutaneous tocilizumab 162 mg was administered without complication. After completion of budesonide/azathioprine, ursodiol was continued long-term for persistent elevation of ALP. Serial ERCPs for plastic biliary stent placement were performed for biliary sludge and for an unresolved CBD stricture. ALP level improved to < 180 U/L about 7-8 months after tocilizumab.

Discussion: Cases of IMCp could be potentially overlooked because ALP is not featured in the society guidelines' assessments for liver toxicity. Although steroids can be used to initially treat IMCp, aggressive escalation to alternative treatments such as tocilizumab is important to mitigate progression to biliary sequelae that might arise. As use of anti-PD-1/L1 agents expand, IMCp may become increasingly common, and prompt treatment is of paramount importance.