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