Introduction Teduglutide (TED) is indicated for the treatment of adults with intestinal failure associated with short bowel syndrome (SBS-IF) who are dependent on parenteral support (PS). In phase III randomised placebo-controlled trials, TED significantly reduced PS volume requirements and number of PS infusion days per week in patients (pts) with SBS-IF. Here, we present combined safety data from TED-treated pts in these trials and their respective open-label extension studies.
Methods Safety data were pooled from 4 TED clinical studies in adult pts with SBS–IF: two 24 week, double-blind, placebo-controlled trials with 2 respective open-label extensions of 28 weeks’ and 2 years’ duration (NCT-00081458, -00798967, -00172185, -0930644).
Results Across 4 studies, 173 pts received subcutaneous TED (0.05 mg/kg/d, n = 134; 0.10 mg/kg/d, n = 39). 140 (81%) were treated with TED for ≥6 months and 111 (64%) were treated for ≥12 months; mean duration of TED exposure was 67 weeks. Most pts (97%) experienced ≥1 treatment-emergent adverse event (TEAE); the majority were mild (53%) or moderate (38%) in severity. TEAEs reported by ≥10% of pts were 42% abdominal pain; 29% upper respiratory tract infection; 27% catheter sepsis or nausea; 20% headaches or asthenic conditions; 19% injection-site reactions; 18.5% abdominal distension or urinary tract infections; 18% gastrointestinal (GI) stoma complications; 17% catheter site–related reactions or febrile disorders; and ≤15% vomiting, musculoskeletal pain, diarrhoea, fluid overload, hypersensitivity, or flatulence. The incidence rates of the most commonly reported GI adverse events (AEs) and fluid overload decreased over treatment time (Table). TEAEs that led to premature discontinuation occurred in 20% of pts (n = 34); the most common was abdominal pain (5%; n = 8). Serious AEs (SAEs) were reported by 58% of pts (n = 101). The only SAE reported in ≥5% of TED-treated pts was catheter sepsis (25%; n = 43). As previously reported, 3 cases of malignant neoplasms occurred (metastatic adenocarcinoma, non–small-cell lung cancer, and squamous cell carcinoma). Metastatic adenocarcinoma was considered treatment related; this pt also had a history of Hodgkin disease treated with chemotherapy and radiation.
Conclusion TED was generally well tolerated in pts with SBS-IF. No new safety signals were identified in the pooled analysis. The most frequently reported AEs were consistent with the underlying disease condition and known mechanism of action of TED and were reported early in the treatment period. Data from phase III trials demonstrate the safety of long-term TED treatment.
Disclosure of Interest None Declared