特度鲁肽长期治疗：48 周开放标签单中心临床研究在短肠综合征患儿中的应用。
Long-term treatment with teduglutide: a 48-week open-label single-center clinical trial in children with short bowel syndrome.
机构信息
Service de Gastro-entérologie et Nutrition pédiatrique, Université Paris Cité, Hôpital Necker-Enfants Malades, Paris.
Service de Gastro-entérologie et Nutrition pédiatrique, Université Paris Cité, Hôpital Necker-Enfants Malades, Paris.
出版信息
Am J Clin Nutr. 2023 Jun;117(6):1152-1163. doi: 10.1016/j.ajcnut.2023.02.019. Epub 2023 May 3.
BACKGROUND
Short bowel syndrome (SBS) is the main cause of intestinal failure in children.
OBJECTIVES
This single-center study evaluated the safety and efficacy of teduglutide in pediatric patients with SBS-associated intestinal failure (SBS-IF).
METHODS
Children with SBS followed at our center with ≥2 y on parenteral nutrition (PN) and with small bowel length <80 cm who had reached a plateau were consecutively included in the study. At baseline, participants underwent a clinical assessment including a 3-d stool balance analysis, which was repeated at the end of the study. Teduglutide was administered subcutaneously 0.05 mg/kg/d for 48 wk. PN dependence was expressed as the PN dependency index (PNDI), which is the ratio PN non-protein energy intake/REE. Safety endpoints included treatment-emergent adverse events and growth parameters.
RESULTS
Median age at inclusion was 9.4 y (range: 5-16). The median residual SB length was 26 cm (IQR: 12-40). At baseline, the median PNDI was 94% (IQR: 74-119), (median PN intake: 38.9 calories/kg/d, IQR: 26.1-48.6). At week 24, 24 (96%) children experienced a reduction of >20% of PN requirements with a median PNDI = 50% (IQR: 38-81), (PN intake: 23.5 calories/kg/d IQR: 14.6-26.2), P < 0.01. At week 48, 8 children (32%) were weaned completely off PN. Plasma citrulline increased from 14 μmol/L (IQR: 8-21) at baseline to 29 μmol/L (IQR: 17-54) at week 48 (P < 0.001). Weight, height, and BMI z-scores remained stable. The median total energy absorption rate increased from 59% (IQR: 46-76) at baseline to 73% (IQR: 58-81) at week 48 (P = 0.0222). Fasting and postprandial endogenous GLP-2 concentrations increased at weeks 24 and 48 compared with baseline. Mild abdominal pain at the early phase of treatment, stoma changes, and redness at the injection site were commonly reported.
CONCLUSIONS
Increased intestinal absorption and PN dependency reduction were observed with teduglutide treatment in children with SBS-IF.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03562130. https://clinicaltrials.gov/ct2/show/NCT03562130?term=NCT03562130&draw=2&rank=1.
背景
短肠综合征（SBS）是儿童肠衰竭的主要原因。
目的
本单中心研究评估了特利格鲁肽在伴有肠衰竭（SBS-IF）的 SBS 儿童患者中的安全性和疗效。
方法
在我们中心接受治疗的 SBS 儿童，接受肠外营养（PN）≥2 年，小肠长度<80cm 且已达到平台期，连续纳入本研究。在基线时，参与者进行了临床评估，包括 3 天粪便平衡分析，研究结束时重复该分析。特利格鲁肽皮下给药，剂量为 0.05mg/kg/d，持续 48 周。PN 依赖性表示为 PN 依赖性指数（PNDI），即 PN 非蛋白能量摄入/REE 的比值。安全性终点包括治疗中出现的不良事件和生长参数。
结果
中位纳入年龄为 9.4 岁（范围：5-16 岁）。中位剩余 SB 长度为 26cm（IQR：12-40）。基线时，PNDI 中位数为 94%（IQR：74-119），（中位 PN 摄入量：38.9 卡/kg/d，IQR：26.1-48.6）。在第 24 周时，24 名（96%）儿童的 PN 需求减少了>20%，PNDI 中位数为 50%（IQR：38-81），（PN 摄入量：23.5 卡/kg/d，IQR：14.6-26.2），P<0.01。在第 48 周时，8 名儿童（32%）完全停止 PN。血浆瓜氨酸从基线时的 14μmol/L（IQR：8-21）增加到第 48 周时的 29μmol/L（IQR：17-54）（P<0.001）。体重、身高和 BMI z 评分保持稳定。总能量吸收率中位数从基线时的 59%（IQR：46-76）增加到第 48 周时的 73%（IQR：58-81）（P=0.0222）。与基线相比，空腹和餐后内源性 GLP-2 浓度在第 24 周和第 48 周时增加。治疗早期常见轻度腹痛、造口变化和注射部位发红。
结论
在伴有 SBS-IF 的儿童中，特利格鲁肽治疗可增加肠道吸收并减少 PN 依赖性。
试验注册
ClinicalTrials.gov NCT03562130。https://clinicaltrials.gov/ct2/show/NCT03562130?term=NCT03562130&draw=2&rank=1.
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