一项关于ICAM - 1反义寡核苷酸治疗克罗恩病的安慰剂对照试验。

A placebo-controlled trial of ICAM-1 antisense oligonucleotide in the treatment of Crohn's disease.

作者信息

Yacyshyn B R, Bowen-Yacyshyn M B, Jewell L, Tami J A, Bennett C F, Kisner D L, Shanahan W R

机构信息

Division of Gastroenterology, University of Alberta, Edmonton, Canada.

出版信息

Gastroenterology. 1998 Jun;114(6):1133-42. doi: 10.1016/s0016-5085(98)70418-4.

DOI:10.1016/s0016-5085(98)70418-4

PMID:9609749

Abstract

BACKGROUND & AIMS: Intercellular adhesion molecule 1 (ICAM-1) plays an important role in the trafficking and activation of leukocytes and is up-regulated in inflamed mucosa in Crohn's disease. ISIS 2302 is an antisense phosphorothioate oligodeoxynucleotide that inhibits ICAM-1 expression. The aim of this study was to obtain preliminary assessment of tolerability, pharmacology, and efficacy of ISIS 2302 in Crohn's disease.

METHODS

Twenty patients with active, steroid-treated Crohn's disease were randomized (3:1, ISIS 2302 to placebo) to receive over 26 days 13 intravenous infusions of ISIS 2302 (0.5, 1, or 2 mg/kg) or saline placebo in a double-blinded study. The patients were followed up for 6 months.

RESULTS

At the end of treatment. 47% (7 of 15) of ISIS 2302-treated and 20% (1 of 5) of the placebo-treated patients were in remission (Crohn's Disease Activity Index [CDAI] < 150). At the end of month 6, 5 of these 7 ISIS 2302-treated remitters were still in remission, and a 6th patient had a CDAI of 156. Corticosteroid usage was significantly lower (P = 0.0001) in the ISIS 2302-treated patients. These findings were corroborated by significant increases in beta7 and alpha d bearing CD3+ peripheral blood lymphocytes and by decreases in intestinal mucosal ICAM-1 expression during the treatment period.

CONCLUSIONS

ISIS 2302 seems to be a well-tolerated and promising therapy for steroid-treated Crohn's disease.

摘要

背景与目的

细胞间黏附分子1（ICAM - 1）在白细胞的运输和激活中起重要作用，且在克罗恩病的炎症黏膜中上调。ISIS 2302是一种抑制ICAM - 1表达的反义硫代磷酸酯寡脱氧核苷酸。本研究的目的是对ISIS 2302在克罗恩病中的耐受性、药理学和疗效进行初步评估。

方法

在一项双盲研究中，将20例接受类固醇治疗的活动性克罗恩病患者随机分组（3∶1，ISIS 2302组与安慰剂组），在26天内接受13次静脉输注ISIS 2302（0.5、1或2 mg/kg）或生理盐水安慰剂。对患者进行6个月的随访。

结果

治疗结束时，接受ISIS 2302治疗的患者中有47%（15例中的7例）缓解（克罗恩病活动指数[CDAI]<150），接受安慰剂治疗的患者中有20%（5例中的1例）缓解。在第6个月末，这7例接受ISIS 2302治疗的缓解者中有5例仍处于缓解状态，第6例患者的CDAI为156。接受ISIS 2302治疗的患者中皮质类固醇的使用显著减少（P = 0.0001）。治疗期间，β7和αd阳性的CD3 +外周血淋巴细胞显著增加以及肠黏膜ICAM - 1表达降低证实了这些发现。