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

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.

• Authors: L Marthey, C Mateus, C Mussini, M Nachury, S Nancey, F Grange, C Zallot, L Peyrin-Biroulet, J F Rahier, M Bourdier de Beauregard, L Mortier, C Coutzac, E Soularue, E Lanoy, N Kapel, D Planchard, N Chaput, C Robert, F Carbonnel
• Journal: Journal of Crohn's & colitis (J Crohns Colitis) Vol. 10 Issue 4 Pg. 395-401 (Apr 2016) ISSN: 1876-4479 [Electronic] England
• PMID: 26783344 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• CTLA-4 Antigen
• Ipilimumab
• tremelimumab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (adverse effects, immunology, therapeutic use)
• Antibodies, Monoclonal, Humanized
• CTLA-4 Antigen (immunology)
• Colectomy
• Colon (pathology)
• Enterocolitis (chemically induced, immunology, pathology)
• Female
• Humans
• Immunotherapy (adverse effects, methods)
• Inflammatory Bowel Diseases (chemically induced, immunology, pathology)
• Ipilimumab
• Male
• Melanoma (therapy)
• Middle Aged
• Young Adult