Norsa Lorenzo, Ghirardi Arianna, Ramos Boluda Esther, Guz-Mark Anat, Hojsak Iva, Hilberath Johannes, Broekaert Ilse Juia, Sacristán Rocío González, Lezo Antonella, Guerra Paula, Poinsot Pierre, Lambe Cecile, D'Antiga Lorenzo
Paediatric Department, Vittore Buzzi Children's Hospital, University of Milan, Italy.
Pediatric Hepatology Gastroenterology and Transplantation Unit, ASST Papa Giovanni XXIII, Bergamo, Italy.
EClinicalMedicine. 2025 Jul 8;85:103343. doi: 10.1016/j.eclinm.2025.103343. eCollection 2025 Jul.
Teduglutide (TED), a glucagon-like peptide 2 analogue licensed for children with short bowel syndrome (SBS), is increasingly used in the attempt to augment intestinal absorption and lower parenteral nutrition (PN) needs. Data from real-life studies on TED efficacy and predictors of response in children with SBS are limited. This study aimed to define pre-treatment and on-treatment predictors of response, in terms of PN reduction and weaning, in TED treated children with SBS.
In this multicenter cohort study, we collected retrospective and prospective data of children with SBS undergoing TED treatment in 7 countries in Europe (Italy, Spain, Croatia, Germany, France, Israel, Portugal). All children with SBS starting TED treatment and not included in clinical trials were eligible. Information on patients' post-surgical anatomy, amount of PN calories and volume required at baseline and at 3, 6 and 12 months after TED start, along with biochemical markers of PN tolerance and complications, were recorded. The main outcome was predicting factors of 1 year response to TED treatment defined as a reduction of ≥20% of PN needs.
Between 01.06.2021 and 31.05.2023, we collected information on 104 children (64 males, 61.5%; 40 females, 38.5%) the median age at enrolment was 6.7 years old (IQR: 3.6-10.4); at 12 months' follow up after TED start 68 children achieved response (cumulative incidence: 70%, 95% CI 61%-79%), whereas complete PN weaning was achieved in 21 children (cumulative incidence: 22%, 95% CI 15%-31%). Multivariable logistic regression analysis showed that predictors of response were longer residual small bowel length (p = 0.027), higher weight Z-score at baseline (p = 0.0061) and normal liver enzymes (p = 0.010). Pre-treatment PN calories <35 kcal/kg/day (p = 0.044) and citrulline ≥14 μmol/L (p = 0.047) predicted complete PN weaning, as well as haemoglobin and citrulline rise in the first 6 months of treatment (p = 0.014 and p = 0.044 respectively).
In children with SBS, longer residual small bowel, better nutritional status and absence of liver disease were associated with response to teduglutide. Complete PN weaning was predicted by lower calories needs and higher citrulline at baseline. An increase of haemoglobin and citrulline in the first 6 months of treatment were further predictors of complete PN weaning. Even if limited by the real-life design of the study, these findings may guide a tailored indication for the use of teduglutide in children with short bowel syndrome.
The European Society of Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) Networking grant.
替度鲁肽（TED）是一种已获许可用于治疗短肠综合征（SBS）儿童的胰高血糖素样肽2类似物，人们越来越多地使用它来增强肠道吸收并降低肠外营养（PN）需求。关于TED在SBS儿童中的疗效及反应预测因素的真实研究数据有限。本研究旨在确定接受TED治疗的SBS儿童在PN减少和停用方面的治疗前及治疗中反应预测因素。
在这项多中心队列研究中，我们收集了欧洲7个国家（意大利、西班牙、克罗地亚、德国、法国、以色列、葡萄牙）接受TED治疗的SBS儿童的回顾性和前瞻性数据。所有开始接受TED治疗且未纳入临床试验的SBS儿童均符合条件。记录了患者术后解剖结构、基线时以及TED开始后3、6和12个月所需PN热量和体积的信息，以及PN耐受性和并发症的生化指标。主要结局是预测对TED治疗1年反应的因素，定义为PN需求减少≥20%。
在2021年6月1日至2023年5月31日期间，我们收集了104名儿童（64名男性，占61.5%；40名女性，占38.5%）的信息，入组时的中位年龄为6.7岁（四分位间距：3.6 - 10.4岁）；在TED开始后12个月的随访中，68名儿童实现了反应（累积发生率：70%，95%置信区间61% - 79%），而21名儿童实现了完全停用PN（累积发生率：22%，95%置信区间1'5% - 31%）。多变量逻辑回归分析显示，反应的预测因素为残余小肠长度较长（p = 0.027）、基线时体重Z评分较高（p = 0.0061）和肝酶正常（p = 0.010）。治疗前PN热量<35千卡/千克/天（p = 0.044）和瓜氨酸≥14微摩尔/升（p = 0.047）预测了完全停用PN，以及治疗前6个月血红蛋白和瓜氨酸升高（分别为p = 0.014和p = 0.044）。
在SBS儿童中，残余小肠较长、营养状况较好和无肝脏疾病与对替度鲁肽的反应相关。基线时热量需求较低和瓜氨酸较高预测了完全停用PN。治疗前6个月血红蛋白和瓜氨酸升高是完全停用PN的进一步预测因素。即使受该研究的真实设计所限，这些发现可能会为替度鲁肽在短肠综合征儿童中的使用提供个性化的适应证指导。
欧洲儿科胃肠病学、肝病学和营养学会（ESPGHAN）网络基金。
