Quality of life in patients with short bowel syndrome treated with the new glucagon-like peptide-2 analogue teduglutide--analyses from a randomised, placebo-controlled study

Abstract

Background & aims: Short bowel syndrome (SBS)-intestinal failure (IF) patients have impaired quality of life (QoL) and suffer from the burden of malabsorption and parenteral support (PS). A phase III study demonstrated that treatment with teduglutide, a glucagon-like peptide 2 analogue, reduces PS volumes by 32% while maintaining oral fluid intake constant; placebo-treated patients had reduced PS by 21%, but oral fluid intake increased accordingly. As effects of teduglutide on QoL are unknown, they were investigated here.

Methods: QoL analyses from a double-blind, randomised Phase III study in 86 SBS-IF patients receiving teduglutide (0.05 mg/kg/day s.c.) or placebo over 24 weeks. At baseline and every 4 weeks, QoL was assessed using the validated SBS-QoL™ scale.

Results: PS reductions were associated with QoL improvements (ANCOVA, p = 0.0194, SBS-QoL per-protocol). Compared to baseline, teduglutide significantly improved the SBS-QoL™ total score and the score of 9 of 17 items at week 24. These changes were not significant compared to placebo. Teduglutide-treated patients with remaining small intestine >100 cm experienced more gastrointestinal adverse events (GI-AE), unfavourably affecting QoL.

Conclusions: Overall, PS volume reductions were associated with improvements in SBS-QoL™ scores. The short observation period, imbalances in oral fluid intake in relation to PS reductions, large patient and effect heterogeneity and occurrence of GI-AE in a subgroup of teduglutide-treated patients may account for the inability to show statistically significant effects of teduglutide on SBS-QoL™ scores compared to placebo.

Trial registration: ClinicalTrials.gov NCT00798967.

Keywords: Glucagon-like peptide 2 (GLP-2) analogue; Quality of life (QoL); Short bowel syndrome (SBS); Teduglutide; Treatment response.