Vedolizumab for the Treatment of Refractory Severe Rejection in Intestinal Transplantation

Abstract

Introduction: Acute cellular rejection (ACR) is a continuous challenge in intestinal transplantation despite the advent of potent immunosuppressive drugs. Most of the traditional drugs used to treat ACR destroy specific cell lines with important systemic side effects. Migration of the activated recipient lymphocytes (T Cells) to the mucosal surface can trigger ACR in intestinal transplant. It has been demonstrated in a murine model of intestinal transplantation that during ACR allografts are infiltrate by large numbers of α4β7 T cells and the treatment with a blocking antibody specific for β7 significantly reduces the cellular infiltrate and inhibits ACR.[1] Vedolizumab is a humanized monoclonal antibody that binds specifically to the α4β7 integrin, inhibiting T lymphocytes from binding to adhesion molecules (MAdCAM-1), which are expressed mainly in the small bowel and colon. Consequently, vedolizumab can be considered a specific intestinal immunosuppressant, making it especially attractive in intestinal transplantion. Vedolizumab could provide specific down-modulation of the mucosal inflammatory response that is characteristic of IBD and allograft intestinal rejection, thereby allowing re-establishment of homeostasis in the intestinal immune system. Methods: Our group is reporting, to the best of our knowledge, the first report of using Vedolizumab for the treatment of severe ACR in intestinal transplantation. Results: 25 years old, female, with history of Crohn’s disease received an intestinal and colon transplant. After 6 months of follow up patient started missing clinical appointments and presenting undetectable immunosuppressant levels. Eleven months after the transplant patient presented to the ER critically ill. Scope with biopsy was performed showing severely inflamed mucosa, absence of villi, diffuse bleeding and ulcers. All the viral studies were negative. Alemtuzumab 30 mg X 2, Rituximab and steroids were given. After 2 weeks without improvement of symptoms another endoscopic evaluation was performed. Areas of moderate to severe erythematous mucosa without villi, severe friability and active bleeding was found. Patient was over-immunosuppressed and we opted to treat with Vedolizumab (x3). After 10 days from the first dose, a new scope was performed showing regeneration of villi, improved friability and no active bleeding. New scopes showed continuosly improvement of the mucosa followed by resolution of symptoms. PN was weaned and patient was discharged without parenteral support. Conclusions: Vedolizumab was successfully used to rescue a patient with severe rejection after failure of other therapies. It acts specifically in the intestinal mucosa with a much safer side-effect profile. More studies are necessary but it may become an excellent choice to treat or prevent rejection in intestinal transplantation. Reference: 1. Kellersmann R, et al. Monoclonal antibody against beta7 integrins, but not beta7 deficiency, attenuates intestinal allograft rejection in mice. Transplantation 2002 Nov 15;74(9):1327–34