Long-term treatment with teduglutide: a 48-week open-label single-center clinical trial in children with short bowel syndrome.
GLP-2 analog
citrulline
home parenteral nutrition
intestinal failure
parenteral nutrition
parenteral nutrition dependency index
pediatrics
short bowel syndrome
stool balance analysis
teduglutide
Journal
The American journal of clinical nutrition
ISSN: 1938-3207
Titre abrégé: Am J Clin Nutr
Pays: United States
ID NLM: 0376027
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
received:
11
09
2022
revised:
15
02
2023
accepted:
17
02
2023
medline:
5
6
2023
pubmed:
4
6
2023
entrez:
3
6
2023
Statut:
ppublish
Résumé
Short bowel syndrome (SBS) is the main cause of intestinal failure in children. This single-center study evaluated the safety and efficacy of teduglutide in pediatric patients with SBS-associated intestinal failure (SBS-IF). Children with SBS followed at our center with ≥2 y on parenteral nutrition (PN) and with small bowel length <80 cm who had reached a plateau were consecutively included in the study. At baseline, participants underwent a clinical assessment including a 3-d stool balance analysis, which was repeated at the end of the study. Teduglutide was administered subcutaneously 0.05 mg/kg/d for 48 wk. PN dependence was expressed as the PN dependency index (PNDI), which is the ratio PN non-protein energy intake/REE. Safety endpoints included treatment-emergent adverse events and growth parameters. Median age at inclusion was 9.4 y (range: 5-16). The median residual SB length was 26 cm (IQR: 12-40). At baseline, the median PNDI was 94% (IQR: 74-119), (median PN intake: 38.9 calories/kg/d, IQR: 26.1-48.6). At week 24, 24 (96%) children experienced a reduction of >20% of PN requirements with a median PNDI = 50% (IQR: 38-81), (PN intake: 23.5 calories/kg/d IQR: 14.6-26.2), P < 0.01. At week 48, 8 children (32%) were weaned completely off PN. Plasma citrulline increased from 14 μmol/L (IQR: 8-21) at baseline to 29 μmol/L (IQR: 17-54) at week 48 (P < 0.001). Weight, height, and BMI z-scores remained stable. The median total energy absorption rate increased from 59% (IQR: 46-76) at baseline to 73% (IQR: 58-81) at week 48 (P = 0.0222). Fasting and postprandial endogenous GLP-2 concentrations increased at weeks 24 and 48 compared with baseline. Mild abdominal pain at the early phase of treatment, stoma changes, and redness at the injection site were commonly reported. Increased intestinal absorption and PN dependency reduction were observed with teduglutide treatment in children with SBS-IF. ClinicalTrials.gov NCT03562130. https://clinicaltrials.gov/ct2/show/NCT03562130?term=NCT03562130&draw=2&rank=1.
Sections du résumé
BACKGROUND
Short bowel syndrome (SBS) is the main cause of intestinal failure in children.
OBJECTIVES
This single-center study evaluated the safety and efficacy of teduglutide in pediatric patients with SBS-associated intestinal failure (SBS-IF).
METHODS
Children with SBS followed at our center with ≥2 y on parenteral nutrition (PN) and with small bowel length <80 cm who had reached a plateau were consecutively included in the study. At baseline, participants underwent a clinical assessment including a 3-d stool balance analysis, which was repeated at the end of the study. Teduglutide was administered subcutaneously 0.05 mg/kg/d for 48 wk. PN dependence was expressed as the PN dependency index (PNDI), which is the ratio PN non-protein energy intake/REE. Safety endpoints included treatment-emergent adverse events and growth parameters.
RESULTS
Median age at inclusion was 9.4 y (range: 5-16). The median residual SB length was 26 cm (IQR: 12-40). At baseline, the median PNDI was 94% (IQR: 74-119), (median PN intake: 38.9 calories/kg/d, IQR: 26.1-48.6). At week 24, 24 (96%) children experienced a reduction of >20% of PN requirements with a median PNDI = 50% (IQR: 38-81), (PN intake: 23.5 calories/kg/d IQR: 14.6-26.2), P < 0.01. At week 48, 8 children (32%) were weaned completely off PN. Plasma citrulline increased from 14 μmol/L (IQR: 8-21) at baseline to 29 μmol/L (IQR: 17-54) at week 48 (P < 0.001). Weight, height, and BMI z-scores remained stable. The median total energy absorption rate increased from 59% (IQR: 46-76) at baseline to 73% (IQR: 58-81) at week 48 (P = 0.0222). Fasting and postprandial endogenous GLP-2 concentrations increased at weeks 24 and 48 compared with baseline. Mild abdominal pain at the early phase of treatment, stoma changes, and redness at the injection site were commonly reported.
CONCLUSIONS
Increased intestinal absorption and PN dependency reduction were observed with teduglutide treatment in children with SBS-IF.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03562130. https://clinicaltrials.gov/ct2/show/NCT03562130?term=NCT03562130&draw=2&rank=1.
Identifiants
pubmed: 37270289
pii: S0002-9165(23)30194-1
doi: 10.1016/j.ajcnut.2023.02.019
pii:
doi:
Substances chimiques
teduglutide
7M19191IKG
Peptides
0
Gastrointestinal Agents
0
Banques de données
ClinicalTrials.gov
['NCT03562130']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1152-1163Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.