Factors Associated With Response to Teduglutide in Patients With Short-Bowel Syndrome and Intestinal Failure
Factors Associated With Response to Teduglutide in Patients With Short-Bowel Syndrome and Intestinal Failure
复制标题
DOI：
10.1053/j.gastro.2017.11.023
复制
发表时间：
2018-03-01
期刊：
影响因子：
29.4
通讯作者：
Olivier, Clement
中科院分区：
文献类型：
--
作者：
Jeppesen, Palle B.;Gabe, Simon M.;Olivier, Clement
背景与目的：临床研究显示，替度鲁肽可增加短肠综合征（SBS）伴肠功能衰竭患者的尿量，减少肠外支持量需求，增加肠道湿重吸收，减少腹泻。然而，替度鲁肽对肠外支持的影响因患者而异。我们对一项III期安慰剂对照研究进行了事后分析，以确定替度鲁肽对肠外支持容量反应影响最大的患者的特征。方法：根据欧洲临床营养和代谢学会分类系统，我们收集了85例SBS伴肠衰竭患者的数据，这些患者于2008年11月25日至2011年1月4日期间在10个国家的27个研究中心接受了替度鲁肽或安慰剂治疗。根据基线胃肠外支持量、肠道解剖结构（第1组，空肠造口术/回肠造口术;第2组，>= 50%结肠连续性无造口;第3组，其他结肠解剖结构）和疾病特征（炎症性肠病、肠系膜血管疾病或其他疾病）评价胃肠外支持量的变化。使用简单线性回归模型进行相关性分析，报告未校正的r（2）值。使用双侧t检验进行治疗组间比较。研究结果：我们将肠外支持量减少与替度鲁肽治疗和基线肠外支持量相关（y = -0.3870x thorn 90.0279，r2 = 0.61; P < .0001）。组1患者中，替度鲁肽对绝对胃肠外支持量的影响显著更大（减少919 +/- 644 mL/d），不仅与接受安慰剂的患者相比（减少340 +/- 436 mL/d; P = 0.0112），但也与第2组中接受替度格列肽治疗的患者（减少355 +/- 306 mL/d; P = 0.0066）相比。替度鲁肽对第3组患者的影响居中。少数SBS和炎症性肠病患者有结肠连续性（10.5% [ n = 2/19]），而大多数SBS和血管或其他疾病患者有结肠连续性（分别为84.4% [ n = 27/32]和67.6% [ n = 23/34]）。结论：在一项替度鲁肽对SBS患者影响的III期研究数据的事后分析中，我们将肠外支持量减少与基线肠外支持量、肠道解剖结构和SBS特征相关联。这些发现可能会告知这些严重残疾患者的初始肠外支持量调整和管理。
BACKGROUND & AIMS: Clinical studies showed teduglutide to increase urine production and reduce need for parenteral support volume in patients with short bowel syndrome (SBS) with intestinal failure, increasing intestinal wet weight absorption and reducing diarrhea. However, the effects of teduglutide on parenteral support vary among patients. We performed a post hoc analysis of a phase III placebo-controlled study to identify characteristics of patients in whom teduglutide has the largest effects on parenteral support volume response. METHODS: We collected data from 85 patients with SBS with intestinal failure, according to the European Society for Clinical Nutrition and Metabolism classification system, who received teduglutide or placebo between November 25, 2008, and January 4, 2011, at 27 sites in 10 countries. Changes in parenteral support volume were evaluated according to baseline parenteral support volume, bowel anatomy (group 1, jejunostomy/ileostomy; group 2, >= 50% colon-in-continuity without stoma; and group 3, other colon anatomies), and disease features (with inflammatory bowel disease, mesenteric vascular diseases, or other conditions). Correlation analyses were conducted using simple linear regression models, with unadjusted r(2) values reported. Two-sided t tests were used for comparisons between treatment groups. RESULTS: We correlated parenteral support volume reduction with teduglutide treatment and baseline parenteral support volume (y = -0.3870x thorn 90.0279, r2 = 0.61; P < .0001). The effects of teduglutide on absolute parenteral support volume were significantly greater in group 1 patients (reduction of 919 +/- 644 mL/d), not only compared with patients given placebo (reduction of 340 +/- 436 mL/d; P = .0112) but also compared with teduglutide-treated patients in group 2 (reduction of 355 +/- 306 mL/d; P = .0066). Teduglutide had an intermediate effect on patients in group 3. A minority of patients with SBS and inflammatory bowel diseases had colon-in-continuity (10.5% [ n = 2/19]), whereas most patients with SBS and vascular or other diseases had colonin-continuity (84.4% [ n = 27/32] and 67.6% [ n = 23/34], respectively). CONCLUSIONS: In a post hoc analysis of data from a phase III study of the effects of teduglutide on patients with SBS, we associated reduced parenteral support volume with baseline parenteral support volume, bowel anatomy, and SBS features. These findings may inform initial parenteral support volume adjustments and management of these severely disabled patients.