PMID-37364133 – Teduglutide Efficacy and Safety in Infants and Children
Chiba M, Masumoto K, Quirós-Tejeira RE, et al. Teduglutide Efficacy and Safety in Infants and Children With Short Bowel Syndrome-Associated Intestinal Failure. J Pediatr Gastroenterol Nutr. 2023;77(4):525-532.
Quick Reference
| Property | Value |
|---|---|
| PMID | 37364133 |
| DOI | 10.1097/MPG.0000000000003867 |
| Year | 2023 |
| Journal | Journal of Pediatric Gastroenterology and Nutrition |
| Study Type | Phase III RCT |
| Evidence Level | II |
| Sample | Pediatric patients (1-17 years) with SBS-IF across two Phase III studies plus extension |
| Peptide(s) Studied | GLP-2 |
Key Findings
- Two Phase III randomized studies plus an open-label extension evaluated teduglutide 0.05 mg/kg/day SC in children aged 1-17 with SBS-IF
- 57-67% of teduglutide-treated children achieved a clinically meaningful response (>=20% reduction in parenteral support) at 24 weeks
- Two children achieved full enteral autonomy (complete independence from parenteral nutrition) during the study period
- Mean parenteral support volume decreased progressively over the treatment period, consistent with ongoing intestinal adaptation
- Safety profile was manageable: most common adverse events included pyrexia, upper respiratory infections, vomiting, and abdominal pain
- No unexpected safety signals; growth parameters remained appropriate for age throughout the study period
Study Design
Two multicenter, randomized, Phase III clinical trials with an open-label extension. Children aged 1-17 years with SBS-IF requiring parenteral support for >=60 days were enrolled. Teduglutide was administered at 0.05 mg/kg/day subcutaneously. Primary efficacy endpoint was the proportion of patients achieving >=20% reduction in parenteral support at week 24 compared to baseline. Extension study assessed durability and long-term safety.
Limitations
- Small sample sizes inherent to the rare disease population
- No placebo control in all study components (some open-label design elements), making it difficult to separate treatment effect from natural intestinal adaptation
- Pediatric SBS anatomy is highly heterogeneous (varying remnant bowel length, presence of ileocecal valve, colon-in-continuity), limiting generalizability of aggregate results
- Long-term safety data (>2 years) still limited at time of publication
Clinical Relevance
These Phase III studies provided the pivotal evidence for the expanded pediatric indication of teduglutide. The confirmation that 0.05 mg/kg/day produces meaningful reductions in parenteral support in children validates GLP-2 receptor agonism as a therapeutic strategy across age groups. The achievement of enteral autonomy in some children represents a potentially curative outcome for a condition that otherwise requires lifelong parenteral nutrition with its attendant complications (line infections, liver disease, reduced quality of life).
Related
#research #RCT #glp-2 #evidence-level-II