Maintenance of Parenteral Nutrition Volume Reduction, Without Weight Loss, After Stopping Teduglutide in a Subset of Patients With Short Bowel Syndrome

Compher, Charlene; Gilroy, Richard; Pertkiewicz, M.; Ziegler, Thomas R.; Ratcliffe, Sarah J.; Joly, Francisca; Rochling, Fedja A.; Messing, Bernard

doi:10.1177/0148607111414431

Cited by 46 publications

(42 citation statements)

References 17 publications

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“…Subjects with increased (INC) PN requirements by 12 months after stopping teduglutide 46 had a greater ( P = .04) PN volume reduction while on drug compared with those with stable (STABLE) or decreased (DEC) requirements at 12 months off drug (−4.7 vs −1.9 L/wk, respectively). INC had increased ( P < .001) PN requirements at 3, 6, and 12 months off drug vs study end while STABLE/DEC requirements did not change.…”

Section: Resultsmentioning

confidence: 97%

“…High risk of allocation concealment (selection) and blinding of participants and personnel (performance) bias were noted in the open‐label Jeppesen et al, 42 , 43 Iyer et al, 44 and Fujioka et al 45 studies. Risk of blinding of outcome assessment (detection) bias was also high in the Gilroy et al, 38 Compher et al, 46 and Ukleja et al 47 studies since the treatments were known by the outcome assessors.…”

Section: Resultsmentioning

confidence: 99%

“…Three subjects completely weaned from PN by 24 weeks of treatment in the Jeppesen et al trial 48 and remained off of PN 12 months later 46 . Two of these subjects received teduglutide 0.05, and 1 received teduglutide 0.10.…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Teduglutide for Safe Reduction of Parenteral Nutrient and/or Fluid Requirements in Adults

Naberhuis¹,

Tappenden

2015

J Parenter Enteral Nutr

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Teduglutide for Safe Reduction of Parenteral Nutrient and/or Fluid Requirements in Adults

Naberhuis¹,

Tappenden

2015

J Parenter Enteral Nutr

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“…In our cohort, two patients had teduglutide therapy stopped after remaining completely off parenteral support for several months. Both had some part of their colon in place; this may be a positive predictor for stability off teduglutide once the parenteral support is weaned off [33]. …”

Section: Discussionmentioning

confidence: 99%

Safety and Efficacy of Teduglutide (Gattex) in Patients With Crohn’s Disease and Need for Parenteral Support Due to Short Bowel Syndrome–associated Intestinal Failure

Kochar

Long

Shelton

et al. 2017

Journal of Clinical Gastroenterology

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Background Teduglutide is a GLP-2 analogue indicated for treatment of adults with short bowel syndrome (SBS). Due to the rarity of SBS, real-world safety or efficacy data are not available in patients with Crohn’s disease (CD) and SBS treated with teduglutide. Aim To evaluate teduglutide’s safety and efficacy in CD patients with SBS. Methods We conducted a retrospective cohort study at three tertiary centers in the United States between 2012 and 2014. Demographic, clinical and therapeutic data were retrieved from medical record systems. Results Thirteen CD patients were included, eight (62%) of whom were on concomitant immunosuppression. Median duration of teduglutide therapy was 365 days (interquartile range (IQR) 122–482 days) and 9/13 patients (69%) remain on therapy. At teduglutide initiation, 69% were on parenteral nutrition (PN). At conclusion of follow-up, 1 patient was on PN. All patients were on intravenous fluids (IVF) prior to teduglutide; median IVF were 9000ml/week (IQR 7000–14000 ml/week). IVF requirements decreased by a median of 3100 ml/week (IQR 2400–8400 ml/week). Six patients (46%) ceased IVF. Adverse events attributed to teduglutide were obstructive symptoms (n=1), pancreatitis (n=1), asymptomatic lipase and amylase elevation (n=1), nausea (n=1) and abdominal pain (n=1). Catheter-related sepsis occurred in four patients. Conclusion This is the first report evaluating the safety and efficacy of teduglutide in a cohort of CD patients with SBS requiring parenteral support. More of half the cohort was on concomitant immunosuppression. Teduglutide appeared to be safe and the majority of patients were weaned off parenteral support.

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“…Phase III clinical trials have recently demonstrated that, in a randomized placebo-controlled trial, patients given teduglutide, a DPP-IV-resistant GLP-2 analog, had a statistically significant decrease in parenteral nutrition (PN) volume and in some cases were liberated from PN (21). In the near future, a GLP-2 analog will likely become available as an adjunct therapy for patients who suffer from intestinal failure (4,9,21,24,41).…”

mentioning

confidence: 99%

Enteral nutrients potentiate glucagon-like peptide-2 action and reduce dependence on parenteral nutrition in a rat model of human intestinal failure

Brinkman

Murali

Hitt

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent, proglucagon-derived gut hormone that shows promise for the treatment of short bowel syndrome (SBS). Our objective was to investigate how combination GLP-2 + enteral nutrients (EN) affects intestinal adaption in a rat model that mimics severe human SBS and requires parenteral nutrition (PN). Male Sprague-Dawley rats were assigned to one of five groups and maintained with PN for 18 days: total parenteral nutrition (TPN) alone, TPN + GLP-2 (100 μg·kg(-1)·day(-1)), PN + EN + GLP-2(7 days), PN + EN + GLP-2(18 days), and a nonsurgical oral reference group. Animals underwent massive distal bowel resection followed by jejunocolic anastomosis and placement of jugular catheters. Starting on postoperative day 4, rats in the EN groups were allowed ad libitum access to EN. Groups provided PN + EN + GLP-2 had their rate of PN reduced by 0.25 ml/day starting on postoperative day 6. Groups provided PN + EN + GLP-2 demonstrated significantly greater body weight gain with similar energy intake and a safe 80% reduction in PN compared with TPN ± GLP-2. Groups provided PN + EN + GLP-2 for 7 or 18 days showed similar body weight gain, residual jejunal length, and digestive capacity. Groups provided PN + EN + GLP-2 showed increased jejunal GLP-2 receptor (GLP-2R), insulin-like growth factor-I (IGF-I), and IGF-binding protein-5 (IGFBP-5) expression. Treatment with TPN + GLP-2 demonstrated increased jejunal expression of epidermal growth factor. Cessation of GLP-2 after 7 days with continued EN sustained the majority of intestinal adaption and significantly increased expression of colonic proglucagon compared with PN + EN + GLP-2 for 18 days, and increased plasma GLP-2 concentrations compared with TPN alone. In summary, EN potentiate the intestinotrophic actions of GLP-2 by improving body weight gain allowing for a safe 80% reduction in PN with increased jejunal expression of GLP-2R, IGF-I, and IGFBP-5 following distal bowel resection in the rat.

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Maintenance of Parenteral Nutrition Volume Reduction, Without Weight Loss, After Stopping Teduglutide in a Subset of Patients With Short Bowel Syndrome

Abstract: Gastrointestinal anatomy, baseline BMI, and PN volume reduction on-drug predicted change in BMI off-drug. Whether this response would be maintained for a longer time or in the context of a challenging clinical situation has not been evaluated.

Cited by 46 publications

References 17 publications

Teduglutide for Safe Reduction of Parenteral Nutrient and/or Fluid Requirements in Adults

Teduglutide for Safe Reduction of Parenteral Nutrient and/or Fluid Requirements in Adults

Safety and Efficacy of Teduglutide (Gattex) in Patients With Crohn’s Disease and Need for Parenteral Support Due to Short Bowel Syndrome–associated Intestinal Failure

Enteral nutrients potentiate glucagon-like peptide-2 action and reduce dependence on parenteral nutrition in a rat model of human intestinal failure

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