Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA.
Department of Paediatric Gastroenterology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
J Pediatr Gastroenterol Nutr. 2024 Aug;79(2):290-300. doi: 10.1002/jpn3.12276. Epub 2024 Jun 14.
Patients with short bowel syndrome-associated intestinal failure (SBS-IF) require long-term parenteral nutrition and/or intravenous fluids (PN/IV) to maintain fluid or nutritional balance. We report the long-term safety, efficacy, and predictors of response in pediatric patients with SBS-IF receiving teduglutide over 96 weeks.
This was a pooled, post hoc analysis of two open-label, long-term extension (LTE) studies (NCT02949362 and NCT02954458) in children with SBS-IF. Endpoints included treatment-emergent adverse events (TEAEs) and clinical response (≥20% reduction in PN/IV volume from baseline). A multivariable linear regression identified predictors of teduglutide response; the dependent variable was mean change in PN/IV volume at each visit over 96 weeks.
Overall, 85 patients were analyzed; 78 patients received teduglutide in the parent and/or LTE studies (any teduglutide [TED] group), while seven patients did not receive teduglutide in either the parent or LTE studies. Most TEAEs were moderate or severe in intensity in both groups. By week 96, 82.1% of patients from the any TED group achieved a clinical response, with a mean fluid decrease of 30.1 mL/kg/day and an energy decrease of 21.6 kcal/kg/day. Colon-in-continuity, non-White race, older age at baseline, longer duration of teduglutide exposure, and increasing length of remaining small intestine were significantly associated with a reduction in mean PN/IV volume requirements.
In pediatric patients with SBS-IF, teduglutide treatment resulted in long-term reductions in PN/IV requirements. The degree of PN/IV volume reduction depended on the duration of teduglutide exposure, underlying bowel anatomy, and demographics.
患有短肠综合征相关肠衰竭（SBS-IF）的患者需要长期肠外营养和/或静脉输液（PN/IV）以维持液体或营养平衡。我们报告了接受特杜古肽治疗的 SBS-IF 儿科患者在 96 周以上的长期安全性、疗效和反应预测因素。
这是两项开放标签、长期扩展（LTE）研究（NCT02949362 和 NCT02954458）的汇总、事后分析，纳入 SBS-IF 患儿。终点包括治疗出现的不良事件（TEAEs）和临床反应（与基线相比 PN/IV 量减少≥20%）。多变量线性回归确定了特杜古肽反应的预测因素；因变量为 96 周内每次就诊时 PN/IV 量的平均变化。
共有 85 例患者接受分析；78 例患者在亲本和/或 LTE 研究中接受了特杜古肽治疗（任何特杜古肽[TED]组），而 7 例患者在亲本或 LTE 研究中均未接受特杜古肽治疗。两组中大多数 TEDAE 的严重程度为中度或重度。到第 96 周时，任何 TED 组 82.1%的患者达到临床反应，液体减少量平均为 30.1ml/kg/天，能量减少量为 21.6kcal/kg/天。回肠连续性、非白种人、基线时年龄较大、特杜古肽暴露时间较长以及剩余小肠长度增加与平均 PN/IV 需求量减少显著相关。
在 SBS-IF 儿科患者中，特杜古肽治疗可长期减少 PN/IV 需求。PN/IV 量减少的程度取决于特杜古肽暴露的持续时间、基础肠道解剖结构和人口统计学特征。
