硫唑嘌呤与美沙拉嗪预防内镜下复发的克罗恩病患者术后临床复发的疗效和安全性：一项随机、双盲、双模拟、多中心试验的疗效和安全性结果。

Azathioprine versus mesalazine for prevention of postoperative clinical recurrence in patients with Crohn's disease with endoscopic recurrence: efficacy and safety results of a randomised, double-blind, double-dummy, multicentre trial.

机构信息

Abteilung Gastroenterologie and Hepatologie, Universitätsklinik für Innere Medizin III, Abteilung Gastroenterologie and Hepatologie, Waehringer Guertel 18-20, A-1090 Vienna, Austria.

出版信息

Gut. 2010 Jun;59(6):752-9. doi: 10.1136/gut.2009.194159.

DOI:10.1136/gut.2009.194159

PMID:20551460

Abstract

OBJECTIVE

The aim of the study was to compare azathioprine versus mesalazine tablets for the prevention of clinical recurrence in patients with postoperative Crohn's disease (CD) with moderate or severe endoscopic recurrence.

METHODS

This was a 1 year, double-blind, double-dummy, randomised study which took place in 21 gastroenterology centres in Austria, the Czech Republic, Germany and Israel. The study participants were 78 adults with CD who had undergone resection with ileocolonic anastomosis in the preceding 6-24 months without subsequent clinical recurrence and with a Crohn's disease activity index (CDAI) score <200, but with moderate or severe endoscopic recurrence. The study drugs were azathioprine 2.0-2.5 mg/kg/day or mesalazine 4 g/day over 1 year. The primary end point was therapeutic failure during 1 year, defined as a CDAI score > or = 200 and an increase of > or = 60 points from baseline, or study drug discontinuation due to lack of efficacy or intolerable adverse drug reaction.

RESULTS

Treatment failure occurred in 22.0% (9/41) of azathioprine-treated patients and 10.8% (4/37) of mesalazine-treated patients, a difference of 11.1% (95% CI -5.0% to 27.3%, p=0.19). Clinical recurrence was significantly less frequent with azathioprine versus mesalazine (0/41 (0%) vs 4/37 (10.8%), p=0.031), whereas study drug discontinuation due to adverse drug reactions only occurred in azathioprine-treated patients (9/41 (22.0%) vs 0%, p=0.002). The proportion of patients showing > or = 1 point reduction in Rutgeerts score between baseline and month 12 was 63.3% (19/30) and 34.4% (11/32) in the azathioprine and mesalazine groups, respectively (p=0.023).

CONCLUSIONS

In this population of patients with postoperative CD at high risk of clinical recurrence, superiority for azathioprine versus mesalazine could not be demonstrated for therapeutic failure.

摘要

目的

本研究旨在比较硫唑嘌呤与美沙拉嗪片用于预防术后克罗恩病（CD）患者临床复发的疗效，这些患者内镜下存在中重度复发且疾病活动度指数（CDAI）评分＜200。

方法

这是一项为期 1 年的、双盲、双模拟、随机研究，在奥地利、捷克共和国、德国和以色列的 21 个胃肠病学中心进行。该研究纳入了 78 例年龄在 18 至 75 岁之间的 CD 成年患者，这些患者在过去 6-24 个月内接受过回肠结肠吻合术，但没有随后的临床复发，且 CDAI 评分＜200，但内镜下存在中重度复发。研究药物为硫唑嘌呤 2.0-2.5mg/kg/天或美沙拉嗪 4g/天，疗程为 1 年。主要终点为 1 年内治疗失败，定义为 CDAI 评分≥200 分且与基线相比增加≥60 分，或因疗效不佳或无法耐受不良反应而停用研究药物。

结果

22.0%（9/41）的硫唑嘌呤治疗患者和 10.8%（4/37）的美沙拉嗪治疗患者发生治疗失败，差异为 11.1%（95%CI-5.0%至 27.3%，p=0.19）。与美沙拉嗪相比，硫唑嘌呤治疗患者的临床复发率显著降低（0/41（0%）vs 4/37（10.8%），p=0.031），但仅在硫唑嘌呤治疗患者中观察到因不良反应而停药（9/41（22.0%）vs 0%，p=0.002）。在基线和第 12 个月时，Rutgeerts 评分至少降低 1 分的患者比例分别为硫唑嘌呤组 63.3%（19/30）和美沙拉嗪组 34.4%（11/32）（p=0.023）。