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Erschienen in: Drugs 9/2013

01.06.2013 | Adis Drug Evaluation

Teduglutide: A Review of its Use in the Treatment of Patients with Short Bowel Syndrome

verfasst von: Celeste B. Burness, Paul L. McCormack

Erschienen in: Drugs | Ausgabe 9/2013

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Abstract

The recombinant analogue of human glucagon-like peptide-2 (GLP-2) teduglutide (Gattex®, Revestive®) is a novel therapy for short bowel syndrome (SBS). GLP-2 is a naturally occurring hormone that regulates the growth, proliferation and maintenance of cells lining the gastrointestinal tract. Subcutaneous teduglutide is the first long-term medical therapy approved for the treatment of adult patients with SBS who are dependent on parenteral support (parenteral nutrition and/or intravenous fluids). In a pivotal, double-blind, multicentre, phase III study in adult patients with SBS who were dependent on parenteral support, a significantly higher proportion of teduglutide 0.05 mg/kg/day recipients than placebo recipients achieved at least a 20 % reduction from baseline in weekly parenteral support volume at week 20 and maintained at week 24 (primary endpoint). The overall mean reduction in weekly parenteral support volume from baseline was greater in patients who received teduglutide compared with those who received placebo. Additionally, more teduglutide-treated patients achieved at least a one-day reduction in parenteral support than those receiving placebo. Subcutaneous teduglutide had an acceptable tolerability profile; the most frequently reported adverse events were of gastrointestinal origin, consistent with the underlying disease condition and the known mechanism of action of teduglutide.
Literatur
1.
Zurück zum Zitat Buchman AL, Scolapio J, Fryer J. AGA technical review on short bowel syndrome and intestinal transplantation. Gastroenterology. 2003;124(4):1111–34.PubMedCrossRef Buchman AL, Scolapio J, Fryer J. AGA technical review on short bowel syndrome and intestinal transplantation. Gastroenterology. 2003;124(4):1111–34.PubMedCrossRef
2.
Zurück zum Zitat O’Keefe SJ, Buchman AL, Fishbein TM, et al. Short bowel syndrome and intestinal failure: consensus definitions and overview. Clin Gastroenterol Hepatol. 2006;4(1):6–10.PubMedCrossRef O’Keefe SJ, Buchman AL, Fishbein TM, et al. Short bowel syndrome and intestinal failure: consensus definitions and overview. Clin Gastroenterol Hepatol. 2006;4(1):6–10.PubMedCrossRef
3.
Zurück zum Zitat Misiakos EP, Macheras A, Kapetanakis T, et al. Short bowel syndrome: current medical and surgical trends. J Clin Gastroenterol. 2007;41(1):5–18.PubMedCrossRef Misiakos EP, Macheras A, Kapetanakis T, et al. Short bowel syndrome: current medical and surgical trends. J Clin Gastroenterol. 2007;41(1):5–18.PubMedCrossRef
4.
Zurück zum Zitat Drozdowski LA, Clandinin MT, Thomson AB. Morphological, kinetic, membrane biochemical and genetic aspects of intestinal enteroplasticity. World J Gastroenterol. 2009;15(7):774–87.PubMedCrossRef Drozdowski LA, Clandinin MT, Thomson AB. Morphological, kinetic, membrane biochemical and genetic aspects of intestinal enteroplasticity. World J Gastroenterol. 2009;15(7):774–87.PubMedCrossRef
5.
Zurück zum Zitat Jeppesen PB, Hartmann B, Thulesen J, et al. Glucagon-like peptide 2 improves nutrient absorption and nutritional status in short-bowel patients with no colon. Gastroenterology. 2001;120(4):806–15.PubMedCrossRef Jeppesen PB, Hartmann B, Thulesen J, et al. Glucagon-like peptide 2 improves nutrient absorption and nutritional status in short-bowel patients with no colon. Gastroenterology. 2001;120(4):806–15.PubMedCrossRef
6.
Zurück zum Zitat Nightingale J, Woodward JM. Guidelines for management of patients with a short bowel. Gut. 2006;55(Suppl 4):iv1–12. Nightingale J, Woodward JM. Guidelines for management of patients with a short bowel. Gut. 2006;55(Suppl 4):iv1–12.
7.
Zurück zum Zitat Seidner DL, Schwartz LK, Winkler MF, et al. Increased intestinal absorption in the era of teduglutide and its impact on management strategies in patients with short bowel syndrome-associated intestinal failure. JPEN J Parenter Enteral Nutr. 2013;37(2):201–11.PubMedCrossRef Seidner DL, Schwartz LK, Winkler MF, et al. Increased intestinal absorption in the era of teduglutide and its impact on management strategies in patients with short bowel syndrome-associated intestinal failure. JPEN J Parenter Enteral Nutr. 2013;37(2):201–11.PubMedCrossRef
8.
Zurück zum Zitat Steiger E. Guidelines for pharmacotherapy, nutritional management, and weaning parenteral nutrition in adult patients with short bowel syndrome: introduction. J Clin Gastroenterol. 2006;40(Suppl 2):S73–4.PubMedCrossRef Steiger E. Guidelines for pharmacotherapy, nutritional management, and weaning parenteral nutrition in adult patients with short bowel syndrome: introduction. J Clin Gastroenterol. 2006;40(Suppl 2):S73–4.PubMedCrossRef
10.
Zurück zum Zitat McMellen ME, Wakeman D, Longshore SW, et al. Growth factors: possible roles for clinical management of the short bowel syndrome. Semin Pediatr Surg. 2010;19(1):35–43.PubMedCrossRef McMellen ME, Wakeman D, Longshore SW, et al. Growth factors: possible roles for clinical management of the short bowel syndrome. Semin Pediatr Surg. 2010;19(1):35–43.PubMedCrossRef
12.
Zurück zum Zitat Scolapio JS. Short bowel syndrome: recent clinical outcomes with growth hormone. Gastroenterology. 2006;130(2 Suppl 1):S122–6.PubMedCrossRef Scolapio JS. Short bowel syndrome: recent clinical outcomes with growth hormone. Gastroenterology. 2006;130(2 Suppl 1):S122–6.PubMedCrossRef
15.
Zurück zum Zitat Marier JF, Beliveau M, Mouksassi MS, et al. Pharmacokinetics, safety, and tolerability of teduglutide, a glucagon-like peptide-2 (GLP-2) analog, following multiple ascending subcutaneous administrations in healthy subjects. J Clin Pharmacol. 2008;48(11):1289–99.PubMedCrossRef Marier JF, Beliveau M, Mouksassi MS, et al. Pharmacokinetics, safety, and tolerability of teduglutide, a glucagon-like peptide-2 (GLP-2) analog, following multiple ascending subcutaneous administrations in healthy subjects. J Clin Pharmacol. 2008;48(11):1289–99.PubMedCrossRef
16.
Zurück zum Zitat Marier J-F, Mouksassi M-S, Gosselin NH, et al. Population pharmacokinetics of teduglutide following repeated subcutaneous administrations in healthy participants and in patients with short bowel syndrome and Crohn’s disease. J Clin Pharmacol. 2010;50(1):36–49.PubMedCrossRef Marier J-F, Mouksassi M-S, Gosselin NH, et al. Population pharmacokinetics of teduglutide following repeated subcutaneous administrations in healthy participants and in patients with short bowel syndrome and Crohn’s disease. J Clin Pharmacol. 2010;50(1):36–49.PubMedCrossRef
17.
Zurück zum Zitat Hartmann M, Timmer W, Schultz A, et al. A thorough QT study of teduglutide in healthy subjects. Clin Pharmacol Drug Dev. 2012;1(2):57–66. Hartmann M, Timmer W, Schultz A, et al. A thorough QT study of teduglutide in healthy subjects. Clin Pharmacol Drug Dev. 2012;1(2):57–66.
18.
Zurück zum Zitat Berg J, Kim E, Li Y, et al. A randomized, double-blind, placebo-controlled, multiple-dose, parallel-group study to assess the effects of teduglutide on gastric emptying in healthy subjects [abstract no. Sa1959]. Digestive Disease Week 2012 (DDW); 20–22 May 2012; San Diego. Berg J, Kim E, Li Y, et al. A randomized, double-blind, placebo-controlled, multiple-dose, parallel-group study to assess the effects of teduglutide on gastric emptying in healthy subjects [abstract no. Sa1959]. Digestive Disease Week 2012 (DDW); 20–22 May 2012; San Diego.
19.
Zurück zum Zitat Berg JK, Kim EH, Li B, et al. A randomized, double-blind, placebo-controlled study to assess the effects of teduglutide on gastric emptying in healthy subjects [abstract no. 1520397]. American Society for Parenteral and Enteral Nutrition (ASPEN) Clinical Nutrition Week 2013 (CNW13); 9–12 Feb 2013; Phoenix. Berg JK, Kim EH, Li B, et al. A randomized, double-blind, placebo-controlled study to assess the effects of teduglutide on gastric emptying in healthy subjects [abstract no. 1520397]. American Society for Parenteral and Enteral Nutrition (ASPEN) Clinical Nutrition Week 2013 (CNW13); 9–12 Feb 2013; Phoenix.
20.
Zurück zum Zitat Jeppesen PB, Sanguinetti EL, Buchman A, et al. Teduglutide (ALX-0600), a dipeptidyl peptidase IV resistant glucagon-like peptide 2 analogue, improves intestinal function in short bowel syndrome patients. Gut. 2005;54(9):1224–31.PubMedCrossRef Jeppesen PB, Sanguinetti EL, Buchman A, et al. Teduglutide (ALX-0600), a dipeptidyl peptidase IV resistant glucagon-like peptide 2 analogue, improves intestinal function in short bowel syndrome patients. Gut. 2005;54(9):1224–31.PubMedCrossRef
21.
Zurück zum Zitat Jeppesen PB, Gilroy R, Pertkiewicz M, et al. Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome. Gut. 2011;60(7):902–14.PubMedCrossRef Jeppesen PB, Gilroy R, Pertkiewicz M, et al. Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome. Gut. 2011;60(7):902–14.PubMedCrossRef
22.
Zurück zum Zitat Jeppesen PB, Pertkiewicz M, Messing B, et al. Teduglutide reduces need for parenteral support among patients with short bowel syndrome with intestinal failure. Gastroenterology. 2012;143(6):1473–81.PubMedCrossRef Jeppesen PB, Pertkiewicz M, Messing B, et al. Teduglutide reduces need for parenteral support among patients with short bowel syndrome with intestinal failure. Gastroenterology. 2012;143(6):1473–81.PubMedCrossRef
23.
Zurück zum Zitat Wallis K, Walters JRF, Gabe S. Short bowel syndrome: the role of GLP-2 on improving outcome. Curr Opin Clin Nutr Metab Care. 2009;12(5):526–32.PubMedCrossRef Wallis K, Walters JRF, Gabe S. Short bowel syndrome: the role of GLP-2 on improving outcome. Curr Opin Clin Nutr Metab Care. 2009;12(5):526–32.PubMedCrossRef
24.
Zurück zum Zitat Van Citters GW, Lin HC. The ileal brake: a fifteen-year progress report. Curr Gastroenterol Rep. 1999;1(5):404–9.PubMedCrossRef Van Citters GW, Lin HC. The ileal brake: a fifteen-year progress report. Curr Gastroenterol Rep. 1999;1(5):404–9.PubMedCrossRef
25.
Zurück zum Zitat Tappenden KA, Edelman J, Joelsson B. Teduglutide enhances structural adaptation of the small intestinal mucosa in patients with short bowel syndrome. J Clin Gastroenterol. 2013. doi:10.1097/MCG.0b013e3182828f57 Tappenden KA, Edelman J, Joelsson B. Teduglutide enhances structural adaptation of the small intestinal mucosa in patients with short bowel syndrome. J Clin Gastroenterol. 2013. doi:10.​1097/​MCG.​0b013e3182828f57​
26.
Zurück zum Zitat Papadia C, Sherwood RA, Kalantzis C, et al. Plasma citrulline concentration: a reliable marker of small bowel absorptive capacity independent of intestinal inflammation. Am J Gastroenterol. 2007;102(7):1474–82.PubMedCrossRef Papadia C, Sherwood RA, Kalantzis C, et al. Plasma citrulline concentration: a reliable marker of small bowel absorptive capacity independent of intestinal inflammation. Am J Gastroenterol. 2007;102(7):1474–82.PubMedCrossRef
27.
Zurück zum Zitat O’Keefe SJ, Jeppesen PB, Gilroy R, et al. Safety and efficacy of teduglutide after 52 weeks of treatment in patients with short bowel syndrome intestinal failure. Clin Gastroenterol Hepatol. 2013. doi:10.1016/j.cgh.2012.12.029. O’Keefe SJ, Jeppesen PB, Gilroy R, et al. Safety and efficacy of teduglutide after 52 weeks of treatment in patients with short bowel syndrome intestinal failure. Clin Gastroenterol Hepatol. 2013. doi:10.​1016/​j.​cgh.​2012.​12.​029.
29.
Zurück zum Zitat Schwartz L, Fujioka K, Jeppesen PB, et al. Continued improvement and maintenance of parenteral nutrition and/or intravenous fluid support volume reduction in patients with long-term teduglutide treatment: results of an ongoing long-term open-label study [abstract no. 1520168 plus poster]. American Society for Parenteral and Enteral Nutrition (ASPEN) Clinical Nutrition Week 2013 (CNW13); 9–12 Feb 2013; Phoenix. Schwartz L, Fujioka K, Jeppesen PB, et al. Continued improvement and maintenance of parenteral nutrition and/or intravenous fluid support volume reduction in patients with long-term teduglutide treatment: results of an ongoing long-term open-label study [abstract no. 1520168 plus poster]. American Society for Parenteral and Enteral Nutrition (ASPEN) Clinical Nutrition Week 2013 (CNW13); 9–12 Feb 2013; Phoenix.
30.
Zurück zum Zitat Jeppesen PB, Pertkiewicz M, Forbes A, et al. 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. Clin Nutr. 2013. doi:10.1016/j.clnu.2013.03.016.PubMed Jeppesen PB, Pertkiewicz M, Forbes A, et al. 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. Clin Nutr. 2013. doi:10.​1016/​j.​clnu.​2013.​03.​016.PubMed
31.
Zurück zum Zitat Gilroy R, Allard J, Jeppesen PB, et al. Treatment out to 1 year with a GLP-2 analog, teduglutide, safely reduces parenteral nutrition (PN) needs in PN-dependent short bowel syndrome patients [abstract no. 273]. Am J Gastroenterol. 2008;103(s1):S105. Gilroy R, Allard J, Jeppesen PB, et al. Treatment out to 1 year with a GLP-2 analog, teduglutide, safely reduces parenteral nutrition (PN) needs in PN-dependent short bowel syndrome patients [abstract no. 273]. Am J Gastroenterol. 2008;103(s1):S105.
32.
Zurück zum Zitat Fujioka K, Seidner DL, Delmaestro E, et al. Long-term safety and tolerability of teduglutide in patients with intestinal failure associated with short bowel syndrome: combined data from phase III trials [abstract no. 1520553 plus poster]. American Society for Parenteral and Enteral Nutrition (ASPEN) Clinical Nutrition Week 2013 (CNW13); 9–12 Feb 2013; Phoenix. Fujioka K, Seidner DL, Delmaestro E, et al. Long-term safety and tolerability of teduglutide in patients with intestinal failure associated with short bowel syndrome: combined data from phase III trials [abstract no. 1520553 plus poster]. American Society for Parenteral and Enteral Nutrition (ASPEN) Clinical Nutrition Week 2013 (CNW13); 9–12 Feb 2013; Phoenix.
36.
Zurück zum Zitat Buchman AL. Teduglutide and short bowel syndrome: every night without parenteral fluids is a good night. Gastroenterology. 2012;143(6):1416–20.PubMedCrossRef Buchman AL. Teduglutide and short bowel syndrome: every night without parenteral fluids is a good night. Gastroenterology. 2012;143(6):1416–20.PubMedCrossRef
Metadaten
Titel
Teduglutide: A Review of its Use in the Treatment of Patients with Short Bowel Syndrome
verfasst von
Celeste B. Burness
Paul L. McCormack
Publikationsdatum
01.06.2013
Verlag
Springer International Publishing AG
Erschienen in
Drugs / Ausgabe 9/2013
Print ISSN: 0012-6667
Elektronische ISSN: 1179-1950
DOI
https://doi.org/10.1007/s40265-013-0070-y

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