P3973 - Budesonide Can Successfully Treat Bosutanib-Induced Autoimmune Hepatitis

Michael Jorgensen, MD¹, Jonathan L. Steinberg, MD¹, Daniel S. Jamorabo, MD^2
1Stony Brook University Hospital, Stony Brook, NY; ²Stony Brook Medicine, Stony Brook, NY

Introduction: Bosutinib, along with other tyrosine kinase inhibitors (TKI) used to treat Chronic Myelogenous Leukemia (CML), frequently causes a mild drug-induced liver injury (DILI), but no cases of drug-induced autoimmune hepatitis (DI-AIH) have been documented. We report a case of a woman on bosutinib for CML who was diagnosed with DI-AIH and was successfully treated with budesonide monotherapy.

Case Description/Methods: A 68-year-old woman with CML who had developed adverse reactions to three different TKIs was started on bosutinib 100mg daily with good response. Within 3 months her transaminases began to rise, and despite decreasing the bosutinib to every other day they remained consistently elevated for the next year, with peak AST of 106 IU/L. She was thus referred to hepatology clinic.



Extensive liver work up revealed an ANA titer of 1:1280 and an anti-smooth muscle antibody level of 49 ( >30 = moderate to strong positive). There were no stigmata of chronic liver disease or cirrhosis. Subsequent liver biopsy showed interface hepatitis with marked portal/periportal bridging fibrosis and incomplete nodule formation, consistent with a diagnosis of AIH with bridging fibrosis (stage 3 of 4) and possible superimposed DILI.



Due to interactions between azathioprine (AZA) and bosutinib, and the desire to avoid more potent steroids, she was started on budesonide monotherapy 9mg daily; transaminases normalized within 4 months, and remained normal even after decreasing to every-other-day dosing because of loose stools. The patient later held budesonide for a 3-month period due to lower extremity weakness and falls, and her transaminases rose with peak AST 118 IU/L. Budesonide every other day was resumed and her transaminases again normalized with no further side effects.

Discussion: While mild hepatocellular DILI can occur in up to 58% of patients on bosutinib, to our knowledge there are no reports of this medication causing DI-AIH. In this patient with significant immunosuppression from CML, there was a strong desire to avoid more potent steroids. Combination therapy with budesonide and AZA, which improves AIH remission rates with fewer steroid-specific side effects, was planned, however due to potential interactions between bosutinib and AZA, she was treated with budesonide monotherapy with excellent response. This case highlights both a rare drug-induced autoimmune phenomenon, and the importance of individualizing treatment plans based on patient-specific factors.



Disclosures:


Michael Jorgensen, MD¹, Jonathan L. Steinberg, MD¹, Daniel S. Jamorabo, MD². P3973 - Budesonide Can Successfully Treat Bosutanib-Induced Autoimmune Hepatitis, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.