P4450 - A Rare Case of Drug Induced Liver Injury Secondary to Ustekinumab and Risankizumab in a Crohn’s Disease Patient

Shayan Amini, MD¹, Usman Ansari, DO², Mukul Divatia, MD³, Tamneet Basra, MD², Neha Mathur, MD^2
1Houston Methodist-Weill Cornell Graduate School of Medical Sciences, Houston, TX; ²Houston Methodist Hospital, Houston, TX; ³University of Washington Medical Center, Seattle, WA

Introduction: Liver is one of the primary sites of drug metabolism, making it susceptible to drug induced liver injury (DILI). DILI is hypothesized to be due to the binding of drug metabolites to other proteins, mimicking an antigen and inducing T-cell mediated immune response. We report a rare case of DILI in a patient with Crohn’s disease (CD) after therapy with Ustekinumab and Risankizumab.

Case Description/Methods: Patient is a 25-year-old male with fistulizing CD who initially presented in 1/2023 with sepsis secondary to intra-abdominal abscesses, enterocutaneous, and enterovesicular fistulas. He underwent drainage of the abscesses, course of antibiotics, and later underwent surgical fistula takedown and diverting ileostomy. He was started on Ustekinumab in 2/2023 every 8 weeks with excellent response. However, he developed elevated liver function tests (LFTs) with ALT 103 U/L and AST 53 U/L in 6/2023 from normal baseline. Chronic liver disease work-up was unremarkable. MRI enterography showed partial thrombosis in the superior mesenteric vein. He was started on Apixaban with normalization of his LFTs. However, his ALT and AST rose to 107 U/L and 68 U/L one month later. He underwent trans-jugular liver biopsy and pathology was consistent with DILI (Figure 1). Ustekinumab was stopped followed by normalization of LFTs. Patient was transitioned to Risankizumab in 1/2024. After the first induction dose, he developed transaminitis with ALT of 117 U/L and AST of 216 U/L. CT abdomen showed normal liver parenchyma and hepatic vasculature. Further infusion of Risankizumab was held and his LFTs normalized. He is currently being evaluated for an alternative therapy for CD.

Discussion: Ustekinumab and Risankizumab are commonly used for the treatment of CD. Ustekinumab is a monoclonal antibody that inhibits IL-12 and IL-23 by binding to their p40 subunit. Risankizumab inhibits IL-23 through binding to its p23 subunit. DILI is a rare side effect of both medications. Clinical trials with Ustekinumab did not show an increased risk of DILI. Similarly, the rate of Risankizumab induced liver injury was ≤2% in clinical trials. Despite low risk of hepatotoxicity, our patient developed DILI with both medications. Thus, DILI should be considered in the differential diagnosis of CD patients who develop transaminitis while on Ustekinumab or Risankizumab.



Disclosures:


Shayan Amini, MD¹, Usman Ansari, DO², Mukul Divatia, MD³, Tamneet Basra, MD², Neha Mathur, MD². P4450 - A Rare Case of Drug Induced Liver Injury Secondary to Ustekinumab and Risankizumab in a Crohn’s Disease Patient, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.