Post Hoc Analysis of Polyps in 9 Short Bowel Syndrome Patients Treated with Teduglutide

Abstract

Introduction: Preclinical data raise the possibility that teduglutide may be associated with a risk of small intestinal and/or colonic neoplasia. This report aims to evaluate data from 2 clinical trials in patients with short bowel syndrome (SBS) who reported polyps at baseline or during long-term teduglutide treatment. Methods: Post hoc analysis of data was reported in patient e-case forms (eCRFs) regarding gastrointestinal polyps at baseline and over the course of 2 therapeutic trials of teduglutide (STEPS: NCT00798967, EudraCT2008-006193-15; STEPS-2: NCT00930644, EudraCT2009-011679-65). A baseline colonoscopy was required unless a normal colonoscopy had been performed <6 months before screening. Patients with benign polyps removed pre-randomization were eligible for enrollment. Results: Of the patients enrolled (STEPS, n=86; STEPS-2, n=88), 54 who had not undergone prior colectomy received a baseline colonoscopy and 50 received a study completion colonoscopy (remaining patients refused or no colon was present). Baseline colonic polyps were reported in 9 patients (ages 39–75 years; women 67%); per inclusion criteria they were removed before treatment initiation. By the end of STEPS-2, 9 patients (ages 35–63 years; women, 67%) had reported polyps. In 6 of these 9 patients, polyps were recorded as a treatment-emergent adverse event (TEAE). Patients had been on teduglutide for 3 months (1 patient, TEAE), 8 months (1 patient, TEAE), 10 months (1 patient, TEAE), 24 months (5 patients, 3 TEAEs) and 30 months (1 patient, 0 TEAE) at polyp detection. Polyp locations were colon (7 patients), duodenum (1 patient), and unknown (1 patient). Recorded polyp sizes were 2–7 mm (4 patients). 7 patient eCRFs noted that biopsies were performed; 2 recorded low-grade dysplasia (rectal/colorectal polyps), but none recorded overt malignancy. Conclusion: Polyps were reported in 9 of 50 patients receiving long-term teduglutide who had a colonoscopy at study completion (106.3 patient-years exposure). There were no reports of malignancy related to the presence of these polyps. Additional information regarding polyp incidence will be acquired from an ongoing SBS registry. Shire International GmbH, Zug, Switzerland.