Outcomes of Use of Advanced Therapies in the Management of Inflammatory Bowel Disease Post-liver Transplant

Background:
Patients with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC) may require liver transplantation for management of underlying liver disease. There is overlap in medical therapies used for immunosuppression following liver transplantation and IBD; however, patients often require additional IBD-directed therapies for disease management. Anti-tumor necrosis factor (TNF) agents have been the mainstay of treatment for moderate to severe IBD. However, there is limited data on the effectiveness of other advanced therapies such as anti-integrin and anti-interleukin agents, and Janus kinase inhibitors. As there is limited published data on the management of IBD in the post-liver transplant period, we aimed to describe the outcomes of advanced IBD therapies in the post-transplant setting in patients with PSC and IBD.
Methods:
Using large prospective registries of patients with PSC with and without IBD at our institution, 526 patients were identified with PSC and IBD who underwent liver transplantation. Relevant demographic and clinical data were abstracted.
Results:
Two hundred forty-seven patients met inclusion criteria (32.4% female) after excluding patients with prior colectomy predating liver transplant, absence of colonoscopy reports available for review, and/or death within a year of liver transplant. Most had ulcerative colitis (UC) (89.5%) with median age at UC diagnosis of 36 years. Of these, most had extensive colitis (96.4%). IBD was more often diagnosed prior to liver transplant (82.4%). The most common IBD-directed therapy prior to liver transplant was 5-aminosalicylate (5-ASA) agents (56.7%). Only 19 (7.7%) patients were on anti-TNF therapy prior to transplant. Fourteen (5.7%) patients were on >3 or more IBD-related medical therapies prior to transplant. Median age at liver transplantation was 49 years in those with UC. Sixty-six patients with UC (29.9%) had a history of liver allograft-related rejection, 16 (7.2%) required a second liver transplant, and 31 (14%) had recurrent PSC. The most common immunosuppressant agent used following liver transplant was tacrolimus (65.6%). Following liver transplantation, most patients were continued on 5-ASA agents (74.9%) with the addition of vedolizumab in 30 (12.1%) followed by infliximab in 21 (8.5%), adalimumab in 11 (4.5%), ustekinumab in 8 (3.2%), upadacitinib in 4 (1.6%), risankizumab in 2 (0.8%), certolizumab in 1 (0.4%), and golimumab in 1 (0.4%) patient(s). Eighteen (7.3%) patients required more than 1 advanced therapy for management of IBD in the post-transplant period. In those on vedolizumab and infliximab, endoscopic and histologic improvements were demonstrated on follow-up. Thirty-one (12.6%) patients required colectomy following liver transplant for colorectal dysplasia.
Conclusions:
There are currently no randomized controlled studies or retrospective comparative studies evaluating the use of advanced therapies in patients with IBD after liver transplant. Based on the current literature and with the findings in this study, use of anti-TNF and anti-integrin therapy seem to be safe and effective after liver transplantation. It is unclear if endoscopic and/or histologic response rates are higher in the transplant population in comparison to the general IBD population without liver transplant in the setting of baseline immunosuppression post-transplant. Further studies comparing response and remission rates between these populations are needed.