Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
JPEN J Parenter Enteral Nutr. 2020 May;44(4):621-631. doi: 10.1002/jpen.1690. Epub 2019 Sep 8.
This study evaluated the safety and efficacy of teduglutide in pediatric patients with short bowel syndrome-associated intestinal failure (SBS-IF).
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.
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.
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.
本研究评估了特杜古肽在短肠综合征相关肠衰竭（SBS-IF）的儿科患者中的安全性和疗效。
采用 24 周、3 期试验，有 2 个随机、双盲特杜古肽剂量组和一个非盲标准治疗（SOC）组；患者每天接受 0.025mg/kg 或 0.05mg/kg 的特杜古肽。安全性终点包括治疗出现的不良事件（TEAEs）和生长参数。主要疗效/药效学终点为第 24 周时达到 PS 减少≥20%的患者比例。
所有 59 名入组患者均完成了研究（0.025mg/kg，n=24；0.05mg/kg，n=26；SOC，n=9）。各组基线人口统计学和疾病特征具有可比性。TEAEs 分别在特杜古肽组和 SOC 组的 98%和 100%的患者中报告。特杜古肽治疗组最常见的 TEAEs 是发热和呕吐。接受 0.025mg/kg 特杜古肽、0.05mg/kg 特杜古肽和 SOC 的患者中，分别有 13 名（54.2%）、18 名（69.2%）和 1 名（11.1%）达到主要终点（P＜0.05 vs SOC）。0.025mg/kg 和 0.05mg/kg 特杜古肽组在 PS 量（P＜0.05 vs SOC）、PS 热量、每周 PS 输注天数和每天 PS 输注小时数方面均显示出临床意义上的显著减少，并且在第 24 周与基线相比，肠内营养和血浆瓜氨酸增加。2 名（8.3%，0.025mg/kg 特杜古肽）和 3 名（11.5%，0.05mg/kg 特杜古肽）患者实现了肠内自主。
特杜古肽的安全性与之前在儿童和成人中报道的安全性相似。在 24 周的时间内，特杜古肽治疗与 SBS-IF 儿科患者 PS 的显著减少相关。
