Original Article

Flexible Sigmoidoscopy Rather than Colonoscopy Is Adequate for the Diagnosis of Ipilimumab-Associated Colitis

Authors: J. Daniel Herlihy, MD, Stephen Beasley, MD, Andrew Simmelink, MD, Vinaya Maddukuri, MD, Asim Amin, MD, Michal Kamionek, MD, Carl Jacobs, MD, Krista Bossi, MS, Martin Scobey, MD

Abstract

Objectives: Treatment with ipilimumab, a cytotoxic T lymphocyte antigen-4 approved for metastatic melanoma can result in clinically significant immune-mediated drug injury in the form of colitis. Timely diagnosis and response are essential for optimal management. The aims of our study were to determine the percentage of our patients with ipilimumab-associated colitis in which the colitis could be diagnosed by flexible sigmoidoscopy only and to describe the variations in endoscopic and histologic findings as well as the patients’ clinical courses.

Methods: We retrospectively reviewed 244 patients with metastatic melanoma, treated them with ipilimumab, and characterized the endoscopic and histologic features for those who developed colitis.

Results: Of the 68 patients who presented with diarrhea, 33 were diagnosed as having ipilimumab-associated colitis. Endoscopically, all of them had involvement of the left side of the colon; none of the patients were noted to have isolated right colon involvement.

Conclusions: Ipilimumab-associated colitis can be diagnosed with a flexible sigmoidoscopy alone, obviating the need for full colonoscopy.
Posted in: Gastroenterology56 Colonic And Anorectal Disease8

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References

1. Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010;363:711-723.
2. Márquez-Rodas I, Cerezuela P, Soria A, et al. Immune checkpoint inhibitors: therapeutic advances in melanoma. Ann Transl Med 2015;3:267.
3. Weber JS, Kä KC, Hauschild A. Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol 2012;30:2691-2697.
4. Ribas A. Anti-CTLA4 antibody clinical trials in melanoma. Update Cancer Ther 2007;2:133-139.
5. Spain L, Diem S, Larkin J. Management of toxicities of immune checkpoint inhibitors. Cancer Treat Rev 2016;44:51-60.
6. Gupta A, De Felice KM, Loftus EV, et al. Systematic review: colitis associated with anti-CTLA-4 therapy. Aliment Pharmacol Ther 2015;42:406-417.
7. Tarhini A. Immune-mediated adverse events associated with ipilimumab ctla-4 blockade therapy: the underlying mechanisms and clinical management. Scientifica (Cairo) 2013;2013:857519.
8. Beck KE, Blansfield JA, Tran KQ, et al. Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4. J Clin Oncol 2006;24:2283-2289.
9. Johnston RL, Lutzky J, Chodhry A, et al. Cytotoxic T-lymphocyte-associated antigen 4 antibody-induced colitis and its management with infliximab. Dig Dis Sci 2009;54:2538-2540.
10. Slangen ME, van de Eertwegh AJ, van Bodegraven AA, et al. Diarrhoea in a patient with metastatic melanoma: ipilimumab ileocolitis treated with infliximab. World J Gastrointest Pharmacol Ther 2013;4:80-82.
11. Bamias G, Delladetsima I, Perdiki M, et al. Immunological characteristics of colitis associated with anti-CTLA-4 antibody therapy. Cancer Invest 2017;35:443-455.
12. Burdine L, Lai K, Laryea JA. Ipilimumab-induced colonic perforation. J Surg Case Rep 2014;2014:rju010.
13. Khirfan K, Kistin M. Colitis associated with biological agents. Dig Dis Sci 2014;59:1112-1114.
14. Verschuren EC, van den Eertwegh AJ, Wonders J, et al. Clinical, endoscopic, and histologic characteristics of ipilimumab-associated colitis. Clin Gastroenterol Hepatol 2016;14:836-842.
15. Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Bethesda, MD: National Cancer Institute; 2010.
16. Cotton PB, Williams CJ, Hawes RH, et al. Practical Gastrointestinal Endoscopy, 6th ed. New York: Wiley-Blackwell; 2011.
17. Berman D, Parker SM, Chasalow SD, et al. Blockade of cytotoxic T-lymphocyte antigen-4 by ipilimumab results in dysregulation of gastrointestinal immunity in patients with advanced melanoma. Cancer Immun 2010;10:11.
18. Marthey L, Mateus C, Mussini C, et al. Cancer immunotherapy with anti-CTLA-4 monoclonal antibodies induces an inflammatory bowel disease. J Crohns Colitis 2016;10:395-401.
19. Allen TR, Lavanya G. A review on clinicopathological correlation between classical inflammatory bowel disease and immunotherapy related inflammatory bowel disease. https://www.omicsonline.org/open-access/a-review-on-clinicopathological-correlation-between-classical-inflammatory-bowel-disease-and-immunotherapy-related-inflammatory-bowel-disease-1745-7580.1000074.pdf. Accessed December 11, 2018.