A randomised placebo-controlled multicentre trial of intravenous semapimod HCl for moderate to severe Crohn's disease
A randomised placebo-controlled multicentre trial of intravenous semapimod HCl for moderate to severe Crohn's disease
复制标题
DOI：
10.1136/gut.2009.179994
复制
发表时间：
2010-06-01
期刊：
影响因子：
24.5
通讯作者：
Hommes, Daniel
中科院分区：
文献类型：
--
作者：
Dotan, Iris;Rachmilewitz, Daniel;Hommes, Daniel
目的探讨赛匹莫德（Semapimod）治疗中重度克罗恩病（CD）的最佳剂量。方法采用随机、双盲、安慰剂对照试验（CD 04）和开放性扩展试验（CD 05）。该试验在国际多中心门诊进行，纳入了中重度CD患者（克罗恩病活动指数（CDAI）250-400）。安慰剂给药3天; 60 mg semapimod静脉给药1天，安慰剂给药2天;或60 mg semapimod静脉给药3天。完成CD 04的参与者可以参加开放标签扩展研究CD 05，接受最多5次额外的semapimod HCl 60 mg每日剂量，每6-8周3次。主要结果指标为CDAI、炎症性肠病问卷（IBDQ）、克罗恩病内镜炎症评分（CDEIS）和血清C反应蛋白（CRP）浓度。对于CDAI（p=0.82）、IBDQ（p = 0.85）、CDEIS（p =0.57）和CRP（p=0.40），1天和3天方案的应答与安慰剂相似。唯一值得注意的治疗相关安全性发现是输注反应（静脉炎）：安慰剂组、1天和3天semapimod治疗组分别为7.3%、34.8%和62.7%（p
Objective Semapimod, a small molecule known to inhibit proinflammatory cytokine activity, was studied to determine the optimal dose necessary to achieve a response in patients with moderate to severe Crohn's disease (CD).Methods A randomised, double-blind, placebo-controlled trial (CD04) was carried out followed by an open-label extension study (CD05). The trial was conducted in international multicentre outpatient clinics and included patients with moderate to severe CD (Crohn's Disease Activity Index (CDAI) 250-400). Placebo was administered for 3 days; 60 mg semapimod intravenously for 1 day with placebo for 2 days; or 60 mg semapimod intravenously for 3 days. Participants who completed CD04 could participate in the open-label extension study, CD05, to receive up to five additional semapimod HCl 60 mg daily doses three times every 6-8 weeks. The main outcome measures were CDAI, Inflammatory Bowel Disease Questionnaire (IBDQ), Crohn's Disease Endoscopic Inflammation Score (CDEIS) and serum C-reactive protein (CRP) concentration.Results 152 patients were randomised in CD04. Responses for 1 and 3 day regimens were similar to placebo for CDAI (p=0.82), IBDQ (p=0.85), CDEIS (p=0.57) and CRP (p=0.40). The only noteworthy treatment-related safety finding was infusion reaction (phlebitis): 7.3, 34.8 and 62.7% for the placebo and 1 and 3 day semapimod treatment groups, respectively (p