S6141 Vedolizumab for Severe Refractory Acute Cellular Rejection After Intestinal Transplantation

Introduction: Despite advances in immunotherapy, acute cellular rejection (ACR) affects 30–40% of adult intestinal transplant (ITx) recipients. ACR is traditionally managed with high-dose corticosteroids and intensified immunosuppression. With the development of monoclonal antibodies targeting CD3, CD20, CD52, IL-2, and TNF-alpha, biologics are increasingly used for induction, maintenance, and anti-rejection therapy. Vedolizumab (VDZ), an anti-integrin α4β7 monoclonal antibody approved for inflammatory bowel disease (IBD), has gut-specific immunomodulatory effects that may offer a therapeutic option in intestinal graft rejection. We present a case of severe, treatment-refractory ACR successfully managed with VDZ. Case Description/Methods: A 19-year-old man developed short bowel syndrome after massive intestinal resection due to an abdominal gunshot wound and subsequently underwent ITx, including small intestine and ascending colon. He was continued on teduglutide, a glucagon-like peptide 2 analog (GLP-2) post-transplant and presented for diverting loop ileostomy reversal 4 months post-ITx. Surgical pathology showed mild ACR, for which infliximab and high-dose methylprednisolone were given. He was discharged on a prednisone taper with ongoing tacrolimus and monthly basiliximab. Two days later, he returned with abdominal pain and distension due to small bowel obstruction. He underwent limited small bowel resection with anastomosis and cecostomy creation. Endoscopy revealed denuded, edematous and ulcerated duodenal and colonic graft mucosa, and histology confirmed severe ACR. He received intravenous VDZ 300 mg, eculizumab 900 mg, and methylprednisolone 500 mg. Within 4 days of VDZ, serial endoscopies showed marked improvement in mucosal edema and inflammation with re-epithelialization. The graft continues to show endoscopic and histologic recovery following 2 doses of VDZ for ACR. Discussion: This case highlights VDZ as a safe and effective treatment option for ACR in ITx. This is the third reported case of VDZ used for ACR in ITx and the first in a non-IBD patient. Our patient responded rapidly to VDZ after failing high-dose methylprednisolone, infliximab and basiliximab. VDZ’s gut-selective mechanism may allow for targeted immunosuppression with fewer systemic effects. Additionally, we postulate that GLP-2 analogs used in the post-transplant period may aid epithelial protection and mucosal recovery during ACR. Further studies are needed to assess long-term efficacy and safety of VDZ in this setting.