Yacyshyn Bruce, Chey William Y, Wedel Mark K, Yu Rosie Z, Paul David, Chuang Emil
Rochester Institute for Digestive Diseases and Science, Rochester, New York, USA.
Clin Gastroenterol Hepatol. 2007 Feb;5(2):215-20. doi: 10.1016/j.cgh.2006.11.001.
BACKGROUND & AIMS: The aim of this study was to compare the safety and efficacy of alicaforsen, a first-generation antisense inhibitor of intercellular adhesion molecule 1, with placebo in subjects with active Crohn's disease, a disorder in which intercellular adhesion molecule 1 is overexpressed.
In 2 identical double-masked, placebo-controlled studies, 331 subjects with active Crohn's disease were treated with either alicaforsen (221 subjects) or placebo (110 subjects) administered via 2-hour intravenous infusion 3 times a week for 4 weeks. Patients then returned for follow-up every 2 weeks. The primary end point was clinical remission by week 12. Secondary end points included clinical response and remission in relation to previous use of other biologics including tumor necrosis factor-alpha antagonists and presence of fistulous disease.
The results, whether combined or analyzed individually, failed to demonstrate statistical significance as a measure of its primary outcome (alicaforsen 33.9% vs placebo 34.5%; P = .89). In addition, no statistical differences in response were observed between alicaforsen and placebo in subjects who were previously treated with anti-tumor necrosis factor-alpha therapy or had baseline fistulizing disease. There were no significant differences in adverse events from placebo apart from a higher infusion reaction rate.
In the subject population studied, alicaforsen failed to demonstrate efficacy in any of its primary outcome measures. Alicaforsen was well-tolerated.
本研究旨在比较第一代细胞间黏附分子1反义抑制剂阿利卡福森与安慰剂在活动性克罗恩病患者中的安全性和有效性,在该疾病中细胞间黏附分子1过度表达。
在2项相同的双盲、安慰剂对照研究中,331例活动性克罗恩病患者接受阿利卡福森治疗(221例患者)或安慰剂治疗(110例患者),通过每周3次、每次2小时静脉输注给药,持续4周。患者随后每2周返回进行随访。主要终点是第12周时的临床缓解。次要终点包括与先前使用其他生物制剂(包括肿瘤坏死因子-α拮抗剂)相关的临床反应和缓解情况以及存在瘘管病的情况。
无论合并分析还是单独分析,结果均未显示作为主要结局指标具有统计学意义(阿利卡福森组为33.9%,安慰剂组为34.5%;P = 0.89)。此外,在先前接受抗肿瘤坏死因子-α治疗或有基线瘘管病的患者中,阿利卡福森与安慰剂之间在反应方面未观察到统计学差异。除了输液反应率较高外,与安慰剂相比,不良事件无显著差异。
在所研究的受试者群体中,阿利卡福森在任何主要结局指标上均未显示出疗效。阿利卡福森耐受性良好。