Infectious Complications in Liver Transplant Patients Exposed to Vedolizumab for the Treatment of Inflammatory Bowel Disease

Abstract

Introduction: Vedolizumab, a gut-selective antibody to α4β7 integrin, received FDA approval in May 2014 for the treatment of moderate to severe ulcerative colitis (UC) and Crohn's disease (CD). While integrated safety data from 6 trials of vedolizumab found low incidence of serious infections, there has yet to be published reports of infectious complications in an immunosuppressed population. Methods: Retrospective analysis of all patients with inflammatory bowel disease (IBD) who underwent liver transplant for primary sclerosing cholangitis (PSC) was performed. Patients exposed to vedolizumab post-liver transplant for the treatment of UC or CD were included. Data collected included patient demographics, IBD characteristics, vedolizumab treatment and duration, immunosuppression regimens for prevention of liver rejection, and infectious complications during vedolizumab therapy. Results: A total of 9 patients (6 UC, 3 CD) were included (Table 1). Eight (89%) were male; median age was 51 years (IQR 42 to 57). Indication for liver transplantation was PSC (n=6) or PSC-related cholangiocarcinoma (n=3). Patients were most commonly on tacrolimus (n=8, 89%) with or without prednisone (n=4, 67%) for prevention of rejection. Vedolizumab was initiated a median of 6 years (IQR 2-12 years) following liver transplantation. Patients had a median exposure time of 5 months (IQR 4.5-11.5 months) to vedolizumab at the time of data collection; the majority of patients (n=6, 67%) were on maintenance therapy as defined by receiving > 4 doses. Concurrent use of steroids and immunomodulator was 33% (n=3) and 0%, respectively. During exposure to vedolizumab, 6 patients (67%) experienced a total of 11 infections (Table 2): acute cholangitis (n=2, 4 infections), Clostridium difficile infection (n=2, 2 infections), and 5 other infections each with one occurrence. Three patients experienced infections that required four hospitalizations and one surgery: acute cholangitis requiring common bile duct stent placement (1) and ERCP for stent exchange (1), C. difficile infection requiring intravenous antibiotics, and a small bowel perforation with resultant fecal peritonitis and intra-abdominal abscess requiring surgical repair of perforation drainage of abscesses.Table: Table. Baseline characteristics of individuals with inflammatory bowel disease post-liver transplant on vedolizumabTable: Table. Infections in individuals with inflammatory bowel disease post-liver transplant on vedolizumabConclusion: Two-thirds of immunosuppressed IBD patients in our cohort of post-liver transplant individuals experienced infectious complications after initiation of vedolizumab. Larger case-control studies are needed to assess the risk of infectious complications in IBD patients receiving concurrent immunosuppressive therapy.