Teduglutide for the treatment of adults with intestinal failure associated with short bowel syndrome: pooled safety data from four clinical trials

Abstract

Background: In multiple clinical studies, teduglutide reduced parenteral support (PS) with a consistent safety profile in adults with short bowel syndrome–associated intestinal failure (SBS–IF). The objective of this study was to assess adverse events (AEs) from a pooled data set. Methods: Safety data from four prospective clinical trials of teduglutide in patients with SBS–IF were assimilated. AEs were evaluated in patient groups based on treatment received in each study and in populations stratified to create distinct subgroups based on aetiology, bowel anatomy and baseline PS volume requirements. Results: Safety data are reported for up to 2.5 years, totalling 222 person-years exposure to teduglutide. In most patients, AEs were reported as mild or moderate in severity in all patient groups and occurred at comparable rates between patients who received teduglutide or placebo. Several common gastrointestinal AEs, including abdominal pain, nausea and abdominal distension, were reported more frequently earlier in the course of treatment, with their frequency declining over time. Fewer gastrointestinal AEs were reported in patients with vascular causes of SBS–IF and patients with most of their colon-in-continuity than in other patient subgroups. Across the patient stratification subgroups, the predominant treatment-emergent AEs for which patients receiving teduglutide had a significantly increased relative risk were abdominal distension and gastrointestinal stoma complication compared with patients receiving placebo. Conclusions: Teduglutide had a safety profile consistent with prior adult data and no new safety concerns were identified. The most frequently reported AEs were gastrointestinal in origin, consistent with the underlying disease condition and intestinotrophic actions of teduglutide. Clinical Trial Registry information: NCT00081458/EudraCT, 2004-000438-35; NCT00798967/EudraCT, 2008-006193-15; NCT00172185/EudraCT, 2004-000439-27; NCT00930644/EudraCT, 2009-011679-65

Early effectivity of teduglutide for the treatment of short bowel sydrome – our first clinical experience

“…2 of these patients [11%] obtained complete independence from PS. Reductions in parenteral support requirements were accompanied by significant increases in mean villus height and crypt depth in this cohort as assessed by direct measurement of biopsies obtained during endoscopy [9]. HPN volume reductions were associated with improvements in quality of life scores for patients with short bowel syndrome treated with teduglutide [10] .…”

“…Teduglutide was associated with a significantly increased risk of gastrointestinal stoma complication compared with placebo. Stoma enlargement was observed in clinical trials and in real-world clinical practice [9] . The strength of the work is that this is the first experience in our country, with very good treatment effectiveness.…”

D-lactic acidosis - a rare complication of short bowel syndrome

“…Pre túto liečebnú stratégiu je však potrebných ešte viac klinických údajov. Novinkou v liečbe SBS je teduglutid, rekombinantný GLP-2 (glukagon like peptide-2) analóg, ktorý zväčšuje absorpčnú plochu zvyšku tenkého čreva a umožňuje postupnú redukciu až ukončenie parenterálneho živenia (40,41).…”

De Novo Development of Distal Jejunal and Duodenal Adenomas After 41 Months of Teduglutide Treatment in a Patient With Short‐Bowel Syndrome: A Case Report

“…Studies in mice have suggested that teduglutide may enhance colonic carcinogenesis 5 . Until now, teduglutide treatment for up to 30 months has not been shown to increase the risk of intestinal neoplasia in human patients without any known preexisting cancer 6,7 . An international registry (NCT01990040) was set up to monitor long‐term safety, and endoscopic surveillance recommendations were suggested specifically to screen and monitor for any increased colonic neoplasia risk.…”

“…5 Until now, teduglutide treatment for up to 30 months has not been shown to increase the risk of intestinal neoplasia in human patients without any known preexisting cancer. 6,7 An international registry (NCT01990040) was set up to monitor long-term safety, and endoscopic surveillance recommendations were suggested specifically to screen and monitor for any increased colonic neoplasia risk. However, these surveillance endoscopies are limited to colonoscopies, which are recommended prior to treatment, yearly during the first 2 years, and, if without significant results, subsequently at a 5-year interval during therapy.…”