Anti-Tumor Necrosis Factor Therapy for Inflammatory Bowel Disease Management in Liver Transplant Recipients

Abstract

Purpose: Ulcerative colitis (UC) or Crohn's disease can be difficult to manage following orthotopic liver transplantation (OLT) despite conventional immunosuppressive therapy. We sought to evaluate the efficacy and safety of antitumor necrosis factor (anti-TNF) agents for the management of inflammatory bowel disease (IBD) following OLT. Methods: All patients with an established diagnosis of UC or Crohn's disease who underwent OLT at the Mayo Clinic between January 1, 1985 and December 30, 2009 were identified. Patients were included if they had received anti-TNF therapy post-OLT. Medical records were reviewed to obtain patient demographic, clinical, and outcomes data. Response was defined as a clinician's assessment of improvement after 12 weeks of usage and mucosal healing was defined as the absence of ulcerations on follow-up endoscopy. Results: Of the 8 patients identified, median age was 42 years and 38% were females. All patients had an IBD diagnosis prior to OLT, 3 with UC and 5 with Crohn's disease. Median IBD disease duration was 17 years (range, 5-48 years). All patients underwent OLT for primary sclerosing cholangitis (PSC), 3 also had cholangiocarcinoma. Three patients had received anti-TNF therapy before OLT, but no anti-TNF agents were continued at the time of OLT. Median time from OLT to anti-TNF usage was 3.5 years (range, 1-14 years). Agents administered included infliximab (n=4), infliximab followed by adalimumab (n=2), and adalimumab (n=2). Reasons for changing from infliximab to adalimumab included infusion reaction (n=1) and loss of response (n=1). The most common indications for anti-TNF agents were diarrhea (n=6), diarrhea with penetrating disease (n=1), and diarrhea with extra-intestinal disease manifestations (n=1). Clinical response was demonstrated in 7 of 8 patients with initial therapy. Of the two patients changed to adalimumab, only one demonstrated a clinical response (patient with infliximab allergy). Mucosal healing was demonstrated in 3 of 7 patients. Five patients were tapered off prednisone. Four infections in 3 patients were reported while on anti-TNF therapy, including oral candidiasis, Clostridium difficile colitis, pneumonia, and cryptosporidiosis. One individual developed an Epstein-Barr virus-positive polymorphic post-transplant lympho-proliferative disorder in the absence of depleting antilymphocyte therapy. No organ rejection was reported while on anti-TNF therapy. One death occurred due to complications from recurrent PSC. Conclusion: Initiation of anti-TNF therapy post-OLT appears to be an effective option for IBD management. Further studies are needed to adequately assess potential risks. Disclosure: Dr Bruining: Centocor-past research support.