Teduglutide, a Novel Mucosally Active Analog of Glucagon-Like Peptide-2 (GLP-2) for the Treatment of Moderate to Severe Crohn's Disease
Teduglutide, a Novel Mucosally Active Analog of Glucagon-Like Peptide-2 (GLP-2) for the Treatment of Moderate to Severe Crohn's Disease
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DOI：
10.1002/ibd.21117
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发表时间：
2010-06-01
影响因子：
4.9
通讯作者：
Abou-Assi, Souheil G.
中科院分区：
文献类型：
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作者：
Buchman, Alan L.;Katz, Seymour;Abou-Assi, Souheil G.
背景：替度鲁肽是胰高血糖素样肽 2 (GLP-2) 的类似物，与肠粘膜的营养作用有关。在一项试验性、随机、安慰剂对照、双盲、剂量范围研究中评估了其在治疗活动性克罗恩病 (CD) 中的作用。方法：将中重度 CD 受试者以 1:1:1:1 的比例随机分配至安慰剂组或 3 剂替度鲁肽中的 1 剂（每天 0.05、0.10 或 0.20 mg/kg），每日皮下注射，持续 8 周。主要结果指标是每组中对治疗有反应的受试者百分比，定义为克罗恩病活动指数 (CDAI) 评分下降至 100 分。在第 8 周，有一个可选的 12 周开放标签治疗期，使用替度鲁肽 0.10 mg/kg/d。 结果：100 名受试者入组，其中 71 名完成了研究。平均基线 CDAI 评分为 290.8 +/- 57.6，各组之间相似。与安慰剂相比，所有替度鲁肽治疗组的缓解率和缓解率在数字上均较高，但达到临床缓解或缓解的受试者比例更大，并且最早在最高剂量（0.2 mg/kg/d）组治疗第 2 周就出现了这种情况（44% 缓解和 32% 缓解，而安慰剂组为 32% 缓解和 20% 缓解）。在高剂量组的 8 周安慰剂对照阶段未获得缓解的受试者中，50% 在更长的开放标签治疗阶段获得缓解。基线时各组血浆瓜氨酸相似，但与安慰剂相比，第 8 周时所有替度鲁肽组的血浆瓜氨酸均显着增加。安慰剂组和活性治疗组之间的不良事件没有差异。结论：替度鲁肽是一种新颖且潜在有效的疗法，可诱导活动性中至重度 CD 患者缓解和粘膜愈合。有必要对该生长因子进行进一步的临床研究。
Background: Teduglutide, an analog of glucagon-like peptide-2 (GLP-2), is associated with trophic effects on gut mucosa. Its role in the treatment of active Crohn's disease (CD) was assessed in a pilot, randomized, placebo-controlled, double-blinded, dose-ranging study.Methods: Subjects with moderate-to-severe CD were randomized 1:1:1:1 to placebo or 1 of 3 doses of teduglutide (0.05, 0.10, or 0.20 mg/kg daily) delivered as a daily subcutaneous injection for 8 weeks. The primary outcome measure was the percentage of subjects in each group that responded to treatment, defined as a decrease in Crohn's Disease Activity Index (CDAI) score to 100 points. At week 8 there was an optional 12-week open-label period of treatment with teduglutide 0.10 mg/kg/d.Results: One hundred subjects were enrolled and 71 completed the study. The mean baseline CDAI score was 290.8 +/- 57.6 and was similar across groups. There were numerically higher response and remission rates in all teduglutide-treated groups as compared with placebo, although the percentage of subjects who achieved a clinical response or remission was more substantial, and seen as early as week 2 of treatment in the highest dose (0.2 mg/kg/d) group (44% response and 32% remission versus 32% response and 20% remission in the placebo group). Of subjects who had not achieved remission during the 8-week placebo-controlled phase in the higher-dose group, 50% achieved remission during the more prolonged, open-label treatment phase. Plasma citrulline was similar across groups at baseline, but increased substantially over time in all teduglutide groups when compared with placebo at week 8. Adverse events were not different between placebo and active treatment groups.Conclusions: Teduglutide is a novel and potentially effective therapy for inducing remission and mucosal healing in patients with active moderate-to-severe CD. Further clinical investigation of this growth factor is warranted.