Official Sections CTRMS ISVCA IPITA IPTA ISODP IRTA IXA SPLIT TID

2013 - ISBTS 2013 Symposium


This page contains exclusive content for the member of the following sections: TTS, IXA, ITA

Oral Communications 4

21.315 - Infliximab therapy after intestinal transplantation improves IBD-like chronic mucosal inflammation but is not effective in rescuing severe acute cellular rejection

Presenter: Laura, Wozniak, , United States
Authors: Laura J. Wozniak1, Robert S. Venick1,2, Susan Ponthieux2, Vilayphone Hwang2, Elizabeth A. Marcus1, David A. Ziring1, Martin G. Martin1, Sue V. McDiarmid1,2, Douglas G. Farmer2

Infliximab therapy after intestinal transplantation improves IBD-like chronic mucosal inflammation but is not effective in rescuing severe acute cellular rejection

Laura J. Wozniak1, Robert S. Venick1,2, Susan Ponthieux2, Vilayphone Hwang2, Elizabeth A. Marcus1, David A. Ziring1, Martin G. Martin1, Sue V. McDiarmid1,2, Douglas G. Farmer2

1Pediatric Gastroenterology, UCLA Mattel Children's Hospital, Los Angeles, CA, United States; 2Surgery/Liver and Pancreas Transplantation, David Geffen School of Medicine, Los Angeles, CA, United States

Background: Infliximab is an anti-TNF therapy that has been reported in a few cases to effectively treat refractory acute cellular rejection (ACR) following intestinal transplantation (ITx). Minimal data exists regarding its efficacy for treatment of chronic mucosal inflammation (CMI), defined as an IBD-like condition including active enteritis with a lymphocyte predominant infiltrate and/or ulcerations not attributable to rejection. We have been using infliximab as a rescue agent for severe ACR as well as primary treatment for CMI after ITx. Our aim was to review our experience with these therapies in an effort to examine efficacy. Methods: An IRB-approved, retrospective review was performed using a prospectively maintained single-center database. All ITx were reviewed and any recipient who received infliximab was included. Infliximab therapy was used on a case-by-case basis for patients with severe ACR refractory to standard medical management starting in 2005. In 2007, infliximab was added for recipients with CMI. Infliximab (Remicade®, Janssen Biotech, Inc., Horsham, PA) was administered at 5mg/kg/dose. Doses were administered at 6-8 week intervals for patients with CMI. Results are reported as median (range). Response to therapy was examined over a follow-up time of 3.1 (0.3-6.1) years. Results: Eleven patients (7 with liver-inclusive allografts) were treated with infliximab for 12 different episodes of allograft dysfunction: early severe ACR (n=4), late severe ACR (n=3), and CMI (n=5). Four patients had early ACR diagnosed at 23 (14-46) days post-ITx. Their ACR was initially refractory to antibody therapy, prompting salvage therapy with infliximab at 9 (6-11) days after initial ACR diagnosis. All 4 patients suffered allograft failure. Three patients had late severe exfoliative ACR diagnosed at 11 (8-16) months post-ITx. Despite treatment with ATG and infliximab, allograft rescue was achieved in only 1 patient who later went on to develop CMI. Five patients developed persistent CMI at 1.3 (1-4.8) years post-ITx. Serum testing was negative for HLA donor-specific antibodies, and stool testing was negative for infectious enteritides. Four of 5 improved clinically with infliximab therapy. Two had resolution of CMI after 1 and 7 doses of infliximab, respectively. Two are being treated with ongoing infliximab therapy and have already received 7 and 10 doses, respectively. No severe infusion reactions were experienced. Conclusion: In contrast to published reports, infliximab was not effective as a salvage therapy for early severe ACR that was initially refractory to antibody therapy. Nor was infliximab useful as an adjunctive therapy with ATG for late severe ACR. However, infliximab was highly effective in reversing CMI. Infliximab therapy should be considered as a treatment for patients with CMI after ITx but should be examined further as an adjunct or rescue agent for severe ACR.


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