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Cited by 340

The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.

Cancer Immunotherapy with Anti-CTLA-4 Monoclonal Antibodies Induces an Inflammatory Bowel Disease

Open access
Marthey, L., Mateus, C., Mussini, C., Nachury, M., Nancey, S., Grange, F., Zallot, C., Peyrin-Biroulet, L., Rahier, J. F., Bourdier de Beauregard, M., Mortier, L., Coutzac, C., Soularue, E., Lanoy, E., Kapel, N., Planchard, D., Chaput, N., Robert, C., Carbonnel, F.·2016·Journal of Crohn's and Colitis

Abstract

BACKGROUND: Therapeutic monoclonal anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibodies are associated with immune-mediated enterocolitis. The aim of this study was to provide a detailed description of this entity. METHODS: We included patients with endoscopic signs of inflammation after anti-CTLA-4 infusions for cancer treatment. Other causes of enterocolitis were excluded. Clinical, biological and endoscopic data were recorded. A single pathologist reviewed endoscopic biopsies and colectomy specimens from 27 patients. Patients with and without enterocolitis after ipilimumab-treated melanoma were compared, to identify clinical factors associated with enterocolitis. RESULTS: Thirty-nine patients with anti-CTLA-4 enterocolitis were included (ipilimumab n = 37; tremelimumab n = 2). The most frequent symptom was diarrhoea. Ten patients had extra-intestinal manifestations. Most colonoscopies showed ulcerations involving the rectum and sigmoid, 66% of patients had extensive colitis, 55% had patchy distribution and 20% had ileal inflammation. Endoscopic colonic biopsies showed acute colitis in most patients, while half of the patients had chronic duodenitis. Thirty-five patients received steroids that led to complete clinical remission in 13 patients (37%). Twelve patients required infliximab, of whom 10 (83%) responded. Six patients underwent colectomy (perforation n = 5; toxic megacolon n = 1); one of them died postoperatively. Four patients had a persistent enterocolitis at follow-up colonoscopy. Patients with enterocolitis were more frequently prescribed NSAIDs compared with patients without enterocolitis (31 vs 5%, p = 0.003). CONCLUSIONS: Ipilimumab and tremelimumab may induce a severe and extensive form of inflammatory bowel disease. Rapid escalation to infliximab should be advocated in patients who do not respond to steroids. Patients treated with anti-CTLA-4 should be advised to avoid NSAIDs.

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Metadata

Authors
Marthey, L., Mateus, C., Mussini, C., Nachury, M., Nancey, S., Grange, F., Zallot, C., Peyrin-Biroulet, L., Rahier, J. F., Bourdier de Beauregard, M., Mortier, L., Coutzac, C., Soularue, E., Lanoy, E., Kapel, N., Planchard, D., Chaput, N., Robert, C., & Carbonnel, F.
Venue
Journal of Crohn's and Colitis
Published
2016-01-18
Volume
10
Issue
4
Pages
395-401
ISSN
  • 1873-9946 (ISSN-L)
  • 1876-4479
OpenAlex
W2292645700
Cited by
340
References
7
FWCI
14.37
Type
journal article
Language
en
Open access
bronze

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