David Armstrong1, Alastair Forbes2, Palle B Jeppesen3, Hak-Myung Lee4, Peter Nagy5, Douglas L Seidner6. 1. Division of Gastroenterology & Farncombe Family Digestive Health Research Institute, HSC-3V3, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4K1, Canada. Electronic address: armstro@mcmaster.ca. 2. Norwich Medical School, University of East Anglia, 2.12 Bob Champion Research & Education Bldg, Norwich, England, UK. 3. Department of Medical Gastroenterology, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. 4. Biostatistics & Statistical Programming, Shire Human Genetics Therapies, Inc., a member of the Takeda group of companies, 300 Shire Way, Lexington, MA 02421, USA. 5. Global Clinical Development, Shire International GmbH, a member of the Takeda group of companies, Zahlerweg 10, 6301, Zug, Switzerland. 6. Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, 1211 21st Avenue South, Ste 514 MAB, Nashville, TN, USA.
Abstract
BACKGROUND & AIMS: Teduglutide promotes intestinal growth and is approved for the treatment of short bowel syndrome and intestinal failure (SBS-IF). Based on the pharmacologic activity and preclinical findings, teduglutide can potentially induce proliferative colonic mucosal changes. The aim of this study is to report the occurrence of colorectal polyps in adult patients with SBS-IF who received teduglutide in clinical studies conducted to date. METHODS: A post hoc analysis of the completed Study of Teduglutide Effectiveness in Parenteral Nutrition-Dependent Short Bowel Syndrome Subjects (STEPS) clinical study series (NCT00798967, EudraCT 2008-006193-15; NCT00930644, EudraCT 2009-011679-65; NCT01560403) evaluated electronic case report form data for baseline colonoscopies (performed before treatment) and for surveillance or end-of-study (performed after treatment with teduglutide 0.05 mg/kg/day for 24 and 36 months) post-exposure procedures. RESULTS: In the STEPS studies, 73 patients treated with teduglutide had a baseline colonoscopy. No post-exposure colonoscopy was scheduled in STEPS. In STEPS-2/3, 50 of 65 patients with remnant colon (77%) underwent a protocol-mandated post-exposure colonoscopy. Colon polyps were reported at baseline in 12% (9/73) of patients and post-exposure in 18% (9/50) of patients. Two had polyps both at baseline and post-exposure. On histology, available for 7 patients, 5 had adenomas (1 serrated, 4 tubular) and none had malignancy or high-grade dysplasia. CONCLUSION: These data support recommendations for colonoscopic screening before teduglutide therapy and subsequent on-therapy colonoscopic surveillance for patients with SBS-IF. Further studies are required to assess the risk of polyp formation in patients with SBS-IF and the most appropriate colon polyp surveillance strategies.
BACKGROUND & AIMS:Teduglutide promotes intestinal growth and is approved for the treatment of short bowel syndrome and intestinal failure (SBS-IF). Based on the pharmacologic activity and preclinical findings, teduglutide can potentially induce proliferative colonic mucosal changes. The aim of this study is to report the occurrence of colorectal polyps in adult patients with SBS-IF who received teduglutide in clinical studies conducted to date. METHODS: A post hoc analysis of the completed Study of Teduglutide Effectiveness in Parenteral Nutrition-Dependent Short Bowel Syndrome Subjects (STEPS) clinical study series (NCT00798967, EudraCT 2008-006193-15; NCT00930644, EudraCT 2009-011679-65; NCT01560403) evaluated electronic case report form data for baseline colonoscopies (performed before treatment) and for surveillance or end-of-study (performed after treatment with teduglutide 0.05 mg/kg/day for 24 and 36 months) post-exposure procedures. RESULTS: In the STEPS studies, 73 patients treated with teduglutide had a baseline colonoscopy. No post-exposure colonoscopy was scheduled in STEPS. In STEPS-2/3, 50 of 65 patients with remnant colon (77%) underwent a protocol-mandated post-exposure colonoscopy. Colon polyps were reported at baseline in 12% (9/73) of patients and post-exposure in 18% (9/50) of patients. Two had polyps both at baseline and post-exposure. On histology, available for 7 patients, 5 had adenomas (1 serrated, 4 tubular) and none had malignancy or high-grade dysplasia. CONCLUSION: These data support recommendations for colonoscopic screening before teduglutide therapy and subsequent on-therapy colonoscopic surveillance for patients with SBS-IF. Further studies are required to assess the risk of polyp formation in patients with SBS-IF and the most appropriate colon polyp surveillance strategies.
Authors: Susan Hill; Beth A Carter; Valeria Cohran; Simon Horslen; Stuart S Kaufman; Samuel A Kocoshis; David F Mercer; Russell J Merritt; Mikko P Pakarinen; Susan Protheroe; John F Thompson; Charles P B Vanderpool; Robert S Venick; Paul W Wales; Sharon E Smith; MinJung Yoon; Andrew A Grimm Journal: JPEN J Parenter Enteral Nutr Date: 2021-03-02 Impact factor: 4.016