P787 Use of upadacitinib to treat IBD in post-liver transplant

Abstract

Abstract Background Approximately 2% of patients with inflammatory bowel disease (IBD) have concurrent primary sclerosing cholangitis (PSC). Liver transplantation (LT) is sometimes required due to progressive PSC. However, the management of active IBD post-LT is challenged due to concomitant anti-rejection immunotherapies. Janus kinase inhibition has been previously described to have anti-rejection properties in patients who have had renal transplants. Here, we describe our experience with upadacitinib (UPA), a selective Janus kinase-1 inhibitor, for post-LT active IBD combined with anti-rejection immunosuppression therapy. Methods This is a retrospective, single-center observational study in a tertiary IBD center. We identified patients with LT treated with UPA for their IBD. Patient related outcomes including transplanted liver status and clinical efficacy and safety of UPA for IBD activity were reviewed. Results We identified four patients (3 with Crohn’s disease, 1 with ulcerative colitis) treated with UPA after LT due to PSC, with the UPA indication for the treatment of IBD (n=3) and organ rejection (n=1). Median follow-up was 3 months (interquartile range (IQR) 1.5-7.1), median age at starting UPA was 41.5 years (IQR 40-44), and median interval from the transplant was 3.2 years (IQR 2.3-5.6). Two patients with Crohn’s disease clinically responded to UPA, one weaned off prednisone 30mg/day and remained in clinical remission after reducing UPA from 30 mg/day to 15 mg/day. Two patients developed elevated AST/ALT of up to 107/57 U/L and 83/228 U/L; one required discontinuation of UPA at one month with subsequent AST/ALT normalization; the other remained on UPA with 1.5 month follow-up so far. One UC patient was treated with UPA combined with vedolizumab in an attempt to discontinue prednisone for their immunosuppression for organ rejection, however, they were unable to wean off prednisone due to recurrent ALT and Alk Phos elevations. One patient acquired a mild case of COVID-19 which resolved without change in therapy. No life-threatening adverse events were observed. Conclusion We describe 4 patients with IBD who had LT for PSC and who were treated with UPA with successful management of active IBD in 2 cases but lack of efficacy in one case and liver enzyme elevations limiting UPA use in a second. These findings support further exploration of this novel mechanism for treatment of IBD in the post-LT setting.