Study of teduglutide effectiveness in parenteral nutrition-dependent short-bowel syndrome subjects

Abstract

Loss of intestinal absorptive capacity from congenital defect, surgical resection or mucosal disease results in short bowel syndrome (SBS)-associated intestinal failure. In the past, few medical management options were available besides dietary modification, controlling diarrhea or high stomal output, and providing parenteral fluid, electrolyte and nutrient support (parenteral support). Recent research on strategies to enhance the intestinal absorptive capacity focused on glucagon-like peptide-2, an intestinotrophic hormone that has been shown to increase the villus height and crypt depth, and decrease gastric motility and intestinal secretory losses. STEPS is a Phase III randomized double-blinded controlled trial in which teduglutide, a recombinant analog of glucagon-like peptide-2, or placebo was given subcutaneously to SBS patients for 24 weeks. A clinically meaningful response, defined as a 20–100% reduction in parenteral support volume, was achieved in 63% of the treatment group compared with 30% in the placebo group (p = 0.002) without an increase in serious side effects. Teduglutide offers a new targeted approach to SBS-associated intestinal failure management. Its specific role in clinical practice remains to be evaluated.

Keywords::

• gattex
• glucagon-like peptide-2
• intestinal failure
• short-bowel syndrome
• teduglutide

Financial & competing interests disclosure

SJ O’Keefe had participated in NPS Pharmaceutical’s Scientific Advisory Board in the past and participated in randomized controlled clinical trials of teduglutide supported by NPS. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Short-bowel syndrome-associated intestinal failure (SBS-IF) is a chronic debilitating condition with a significant impact on the patients’ quality of life and huge health care costs.

• • Current medical management of SBS-IF centers on parenteral fluid and nutritional support has serious complications on long-term use.

• • Surgical treatment options including intestinal transplantation are indicated only in a select SBS-IF population and are not widely available.

• • Pharmacological therapy has been symptom directed and limited to conventional antisecretory and antidiarrheal agents.

• • Teduglutide is the first targeted intestinotrophic agent shown to be safe, well tolerated and reduce parenteral support volume and infusion days and may improve the quality of life, and hopefully mitigate serious parenteral nutrition-related complications.

• • Postmarketing drug experience and further clinical trials would validate the efficacy and safety profile and determine the optimal timing of introduction and duration of therapy.