title: Colonic ulcerations may predict steroid-refractory course in patients with ipilimumab-mediated enterocolitis.
abstract: OBJECTIVE
  To investigate management of patients who develop ipilimumab-mediated enterocolitis, including association of endoscopic findings with steroid-refractory symptoms and utility of infliximab as second-line therapy.
  
  
  METHODS
  We retrospectively reviewed all patients at our center with metastatic melanoma who were treated with ipilimumab between March 2011 and May 2014. All patients received a standard regimen of intravenous ipilimumab 3 mg/kg every 3 wk for four doses or until therapy was stopped due to toxicity or disease progression. Basic demographic and clinical data were collected on all patients. For patients who developed grade 2 or worse diarrhea (increase of 4 bowel movements per day), additional data were collected regarding details of gastrointestinal symptoms, endoscopic findings and treatment course. Descriptive statistics were used.
  
  
  RESULTS
  A total of 114 patients were treated with ipilimumab during the study period and all were included. Sixteen patients (14%) developed ≥ grade 2 diarrhea. All patients were treated with high-dose corticosteroids (1-2 mg/kg prednisone daily or equivalent). Nine of 16 patients (56%) had ongoing diarrhea despite high-dose steroids. Steroid-refractory patients received one dose of intravenous infliximab at 5 mg/kg, and all but one had brisk resolution of diarrhea. Fourteen of the patients underwent either colonoscopy or sigmoidoscopy with variable endoscopic findings, ranging from mild erythema to colonic ulcers. Among 8 patients with ulcers demonstrated by sigmoidoscopy or colonoscopy, 7 patients (88%) developed steroid-refractory symptoms requiring infliximab. With a median follow-up of 264 d, no major adverse events associated with prednisone or infliximab were reported.
  
  
  CONCLUSIONS
  In patients with ipilimumab-mediated enterocolitis, the presence of colonic ulcers on endoscopy was associated with a steroid-refractory course.
authors.affiliation: Animesh Jain, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of North Carolina Chapel Hill, Chapel Hill, NC 27599-7080, United States.
authors.forename: Animesh
authors.initials: A
authors.lastname: Jain
authors.affiliation: Animesh Jain, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of North Carolina Chapel Hill, Chapel Hill, NC 27599-7080, United States.
authors.forename: Evan J
authors.initials: EJ
authors.lastname: Lipson
authors.affiliation: Animesh Jain, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of North Carolina Chapel Hill, Chapel Hill, NC 27599-7080, United States.
authors.forename: William H
authors.initials: WH
authors.lastname: Sharfman
authors.affiliation: Animesh Jain, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of North Carolina Chapel Hill, Chapel Hill, NC 27599-7080, United States.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Brant
authors.affiliation: Animesh Jain, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of North Carolina Chapel Hill, Chapel Hill, NC 27599-7080, United States.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lazarev
mesh_terms: D061605:Administration, Intravenous; D000305:Adrenal Cortex Hormones / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology; D003108:Colonic Diseases / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D003113:Colonoscopy; D003967:Diarrhea / Q000188:drug therapy / Q000209:etiology; D004351:Drug Resistance; D004760:Enterocolitis / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D006801:Humans; D000069285:Infliximab / Q000627:therapeutic use; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D011241:Prednisone / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy*; D014456:Ulcer / Q000139:chemically induced / Q000175:diagnosis / Q000276:immunology
chemical_list: D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; D005765:Gastrointestinal Agents; D000074324:Ipilimumab; D000069285:Infliximab; D011241:Prednisone
keywords: Colitis; Colonic ulcer; Corticosteroid; Enterocolitis; Infliximab; Ipilimumab; Melanoma