Safety and Efficacy of Teduglutide in Pediatric Patients With Intestinal Failure due to Short Bowel Syndrome: A 24‐Week, Phase III Study

Abstract

Background: This study evaluated the safety and efficacy of teduglutide in pediatric patients with short bowel syndrome-associated intestinal failure (SBS-IF). Methods: A 24-week, phase III trial with 2 randomized, double-blind teduglutide dose groups and a nonblinded standard of care (SOC) arm was used; patients received 0.025 mg/kg or 0.05 mg/kg teduglutide once daily. Safety end points included treatment-emergent adverse events (TEAEs) and growth parameters. The primary efficacy/pharmacodynamic end point was the number of patients who achieved a ࣙ20% reduction in parenteral support (PS) from baseline at week 24. Results: All 59 enrolled patients completed the study (0.025 mg/kg, n = 24; 0.05 mg/kg, n = 26; SOC, n = 9). Baseline demographics and disease characteristics were comparable among groups. TEAEs were reported by 98% and 100% of patients in the teduglutide and SOC groups, respectively. The most common TEAEs in the teduglutide-treated groups were pyrexia and vomiting. The primary end point was achieved by 13 (54.2%), 18 (69.2%), and 1 (11.1%) patients who received 0.025 mg/kg teduglutide, 0.05 mg/kg teduglutide, and SOC, respectively (P < 0.05 vs SOC). Both 0.025-mg/kg and 0.05-mg/kg teduglutide groups showed clinically significant reductions in PS volume (P < 0.05 vs SOC), PS calories, days per week and hours per day of PS infusions, and increases in enteral nutrition and plasma citrulline at week 24 compared with baseline. Two (8.3%, 0.025 mg/kg teduglutide) and 3 patients (11.5%, 0.05 mg/kg teduglutide) achieved enteral autonomy. Conclusion: The safety profile of teduglutide was similar to that reported previously in children and adults. Treatment with teduglutide was associated with significant reductions in PS for pediatric patients with SBS-IF over 24 weeks.

European Pediatric Surgeon' Association Survey on the Management of Short-Bowel Syndrome

“…24 The safety and a significant efficacy of teduglutide administrated during 24 months in SBS were confirmed in a phase III clinical trial in children. 25 These results in the pediatric population are encouraging; nevertheless, the best time to start GLP2 analogs after bowel resection still needs to be defined.…”

Pediatric short bowel syndrome: state of the problem and current treatment in the Russian Federation

“…Primary endpoint: 69.2% of children after 24-week treatment with 0.05 mg/kg teduglutide once daily achieved ≥20% reduction in parenteral support from baseline. 20% reduction in parenteral support was clinically significant [10].…”

“…Наиболее частые нежелательные явления относятся к специфическим нежелательным явлениям, характерным для агонистов ГПП-2 (рвота, инфекции верхних дыхательных путей, катетер-ассоциированные осложнения, лихорадка, боль в животе). Преждевременного прекращения участия в клиническом исследовании по причине токсичности или нежелательных явлений не было [10].…”

“…Первичная конечная точка: через 24 нед лечения тедуглутидом в дозе 0,05 мг на 1 кг массы тела в сутки 69,2% детей достигли снижения потребности в объеме парентерального питания по меньшей мере на 20%. Снижение на 20% считали клинически значимым [10].…”

Paediatric intestinal failure and transplantation

“…41,42 Data on the impact of teduglutide in children remains restricted to small numbers. 43,44 In children with SBS associated IF, teduglutide for 24 weeks (n = 50) versus standard of care (n = 9) was associated with a ≥20% reduction in administered PN volume in 13 of 24 (54%) and 18 of 26 (69%) patients receiving 0.025 mg/kg or 0.05 mg/kg teduglutide respectively compared to 1 of 9 (11%) receiving standard care. 44 PN calories, days per week and hours per day PN, and increased enteral nutrition was observed in children after 24 weeks' teduglutide therapy compared to baseline.…”