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 r² 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 + 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 colon-in-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. ClinicalTrials.gov no: NCT00798967; ClinicalTrialsRegister.eu no: 2008-006193-15.

中文翻译：

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短肠综合征和肠功能衰竭患者对Teduglutide反应的相关因素

背景与目标

临床研究表明，特德鲁肽可增加患有肠功能衰竭的短肠综合征（SBS）患者的尿量，并减少肠胃外支持剂量的需求，从而增加肠道湿重吸收并减少腹泻。但是，替杜鲁肽对肠胃外支持的作用因患者而异。我们对一项III期安慰剂对照研究进行了事后分析，以确定特德鲁肽对肠胃外支持剂量反应影响最大的患者的特征。

方法

根据欧洲临床营养与代谢分类学会的数据，我们收集了85位肠功能衰竭SBS患者的数据，这些患者在2008年11月25日至2011年1月4日期间在10个国家的27个地点接受了teduglutide或安慰剂治疗。根据基线肠胃外支持量，肠解剖（第1组，空肠造口/回肠造口；第2组，≥50％连续结肠无造口；第3组，其他结肠解剖）和疾病特征评估胃肠外支持量的变化。 （患有炎症性肠病，肠系膜血管疾病或其他疾病）。使用简单的线性回归模型进行相关分析，报告未调整的r ²值。双面t 测试用于治疗组之间的比较。

结果

我们将肠胃外支持量的减少与替度鲁肽治疗和基线肠胃外支持量相关联（y = –0.3870x + 90.0279，r ²  = 0.61；P <.0001）。第1组患者中Teduglutide对绝对胃肠外支持量的影响明显更大（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  = .0112），而且还与第2组接受替度鲁肽治疗的患者进行了比较（降低355±306 mL / d；P = .0066）。替度鲁肽对第3组患者具有中等作用。少数SBS和炎性肠病患者具有结肠持续性（10.5％[n = 2/19]），而大多数SBS和血管性疾病或其他疾病的患者结肠连续性（分别为84.4％[n = 27/32]和67.6％[n = 23/34]）。

结论

在特德鲁肽对SBS患者的III期研究的数据的事后分析中，我们将胃肠外支持量的减少与基线肠胃外支持量，肠道解剖结构和SBS的特征联系起来。这些发现可能会为这些严重残疾患者的初始肠胃外支持量调整和管理提供信息。ClinicalTrials.gov编号：NCT00798967；ClinicalTrialsRegister.eu号：2008-006193-15。