Successful Treatment of Intestinal and Abdominal Wall Rejection with Vedolizumab by Preventing s T-cell Entry

Abstract

Introduction: Intestinal transplantation is an accepted treatment option for patients with end-stage intestinal failure. Despite several improvements in immunosuppressive regimes that are largely adapted from other solid organ programs, rejection of the intestinal graft still far exceeds rejection rates of other solid organs.[1] Vedolizumab is an antibody against the gut homing α4β7 receptor, which prevents entry of various immunological cell types into the intestinal graft.[2] It is approved for use in inflammatory bowel diseases and marketed because of its gut selectivity.[3] Here, we present a case report showing that vedolizumab can prevent both intestinal graft and abdominal wall rejection by inhibiting T-cell entry in the grafts. Case and therapy results: A 24-year old woman with Crohn’s disease developed ultra-short bowel syndrome after several resections with loss of abdominal domain. She was treated for 5 years with total parenteral nutrition (TPN) and developed several episodes of catheter related bloodstream infections, TPN-related liver fibrosis and a low BMI. After thorough review by several experts she underwent a combined intestinal (SB) and abdominal wall (AW) transplantation in March, 2015. Immunosuppression therapy consisted of mycophenolic acid (MMF), prednisolone and tacrolimus. The patient suffered from severe neutropenia on day 15 post-transplant, so MMF was stopped. On day 47, the SB graft showed grade 2 rejection, which was temporarily resolved by a 3-day course of methylprednisolone. On day 68, SB and AW biopsies showed a grade 1 rejection, and because of the antecedent of neutropenia, treatment with vedolizumab (300 mg I.V.) was performed on weeks 0 (day 83), 2, 6 and every 8 weeks thereafter. Rejection resolved in conjunction with a decrease in CD-3 and CD-8 positive cells in both the SB and AW graft. During maintenance phase with vedolizumab, combined with low dose tacrolimus and prednisolone, the patient suffered from gastroenteritis by astrovirus and a primary CMV infection that did not affect the efficacy of the treatment nor the clearance of infections. However, after 6 months, vedolizumab treatment was suspended because of a long-lasting infection with NORO virus. Conclusion: This case report shows that selective blockade of α4β7 with vedolizumab can successfully and relatively safely treat intestinal and abdominal wall rejection.