title: Ipilimumab-induced colitis: experience from a tertiary referral center.
abstract: BACKGROUND
  Ipilimumab is an anticytotoxic T-lymphocyte antigen-4 (CTLA-4) monoclonal antibody used for the treatment of malignant melanoma. It can cause immune-mediated inflammatory adverse events, including diarrhoea and even intestinal perforation or death in clinical trials but there is a dearth of data on postmarketing outcomes.
  
  
  METHODS
  A total of 546 patients attending for treatment of metastatic melanoma between 1 January 2009 and 31 August 2015 were identified by interrogation of the oncology database. A total of 83 of these patients received ipilimumab. Clinical information was extracted from chart reviews, endoscopy and radiology reports, and prescription data.
  
  
  RESULTS
  A total of 83 patients received ipilimumab. Only 19.3% (n = 16) of patients developed a diarrhoeal illness not attributable to other causes. The median grade of diarrhoea among included patients was 2 (range 1-4). In two cases, diarrhoea settled spontaneously without any specific treatment. A total of 87.5% of patients received antidiarrhoeal agents such as loperamide or codeine. These resolved symptoms in all patients with grade 1 diarrhoea. For other treatment, 50% patients received systemic glucocorticosteroids and 31.3% required infliximab. Infliximab resolved symptoms in 100% of cases compared with 50% for systemic glucocorticosteroids.
  
  
  CONCLUSIONS
  The rate of diarrhoea related to ipilimumab in real-world practice is substantial, but below the range observed in data from RCTs. Grade 1 colitis can usually be managed symptomatically, without recourse to stopping ipilimumab. When diarrhoea was grade 2 or above, results from glucocorticosteroids use proved disappointing; but infliximab has been shown to work well. Further research is required into the earlier use of infliximab as an effective treatment for ipilimumab-induced diarrhoea.
authors.affiliation: Leeds Gastroenterology Institute, Bexley Wing, St. James's University Hospital, Beckett Street, Leeds LS9 7TF, UK.
authors.forename: Anthony
authors.initials: A
authors.lastname: O'Connor
authors.affiliation: St James's Institute of Oncology, St. James's University Hospital, Leeds, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Marples
authors.affiliation: St James's Institute of Oncology, St. James's University Hospital, Leeds, UK.
authors.forename: Clive
authors.initials: C
authors.lastname: Mulatero
authors.affiliation: Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.
authors.forename: John
authors.initials: J
authors.lastname: Hamlin
authors.affiliation: Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Ford
keywords: colitis; diarrhoea; infliximab; ipilimumab; melanoma