Safety and Efficacy of Upadacitinib in Patients with Inflammatory Bowel Disease After Liver Transplantation: A Case Series

Purpose Approximately 2% of patients with inflammatory bowel disease (IBD) have primary sclerosing cholangitis (PSC), and some require liver transplantation (LT). Managing IBD after LT is challenging given concomitant anti-rejection immunotherapies. We report our experience using upadacitinib (UPA) to treat patients with IBD after LT. Methods Retrospective, single-center observational study at a tertiary center, identifying patients after LT who received UPA. We assessed efficacy and safety of UPA. Results Four patients after LT (Crohn’s disease n = 3; ulcerative colitis n = 1) received UPA for IBD control ( n = 3) or as a steroid-sparing adjunct for anti-rejection ( n = 1), alongside anti-rejection immunosuppression. Median follow-up from UPA initiation was 10.5 months (IQR 8.9–14.6); age 41.5 years (IQR 40–44); interval from LT 3.2 years (IQR 2.3–5.6). Two receiving prednisone for Crohn’s control at baseline achieved steroid-free remission (Harvey–Bradshaw Index < 5). Three developed liver enzyme elevation: one stopped UPA at one month with subsequent normalization of alanine and aspartate aminotransferase; one underwent liver biopsy showing no rejection and continued UPA with 9-month follow-up; and one receiving UPA for potential anti-organ rejection plus vedolizumab ultimately discontinued UPA for suspected rejection after tapering steroids. One patient experienced mild COVID-19 that resolved without treatment change. No life-threatening adverse events were observed. Conclusion In this small series, UPA controlled IBD activity in 2 of 4 patients after LT but was associated with liver-enzyme elevations in 3, prompting discontinuation in 2. These findings support cautious, closely monitored use and highlight the need for a larger multi-center study of UPA in patients with IBD after LT.