硫唑嘌呤治疗活动性克罗恩病的开放性前瞻性研究

An open prospective trial of azathioprine in treatment of patients with active Crohn＇s disease

目的 通过长程前瞻性研究观察硫唑嘌呤（AZA）治疗我国活动性克罗恩病（CD）患者的疗效及安全性.方法 收集活动性CD且需使用糖皮质激素治疗者60例,开始予AZA及糖皮质激素治疗,激素撤离后以AZA维持治疗.随访监测第12、24、48、72和96周的临床疗效、内镜下黏膜愈合程度及不良反应.结果 随访第12、24、48、72和96周患者的完全缓解率分别为55.0%、66.7%、61.7%、53.3%和53.3%.25例患者治疗前及治疗48周时行结肠镜检查,8例达到黏膜愈合者随访至第96周时均维持完全缓解（8/8）,17例未达黏膜愈合者至第96周时维持完全缓解仅9例（9/17,P=0.026）.比较第48周完全缓解组与未完全缓解组的特征,多因素Logistic回归分析显示治疗后超敏C反应蛋白恢复至正常值为AZA有效维持缓解的独立影响因素（OR=10.1,95%CI：1.8～57.9,P=0.09）.16例（26.7%）患者发生不良反应,其中10例因不良反应而停药;WBC减少为最常见不良反应（18.3%）,发生于用药全程.结论 AZA与糖皮质激素合用可有效诱导活动性CD缓解,AZA可有效维持撤离激素后的长程缓解,AZA最常见的不良反应是WBC减少.部分病例可获得病变肠黏膜愈合,达到黏膜愈合者可维持长程临床缓解.

Objective To evaluate the efficacy and safety of azathioprine （AZA） in long term treatment of patients with active Crohn＇s disease （CD） in China. Methods Sixty patients with active CD,who needed to be treated with systemic steroids, were recruited. All patients initially received AZA combined with steroids therapy and AZA was maintained for treatment after withdrawal of steroids. Clinical efficacy, endoscopic healing of mucosa and adverse events were assessed at the end of the 12th, 24th, 48th, 72th and 96th weeks. Results The complete remission （CR） of the patients at the 12th, 24th, 48th, 72th and 96th weeks was 55.0%, 66. 7%, 61. 7%, 53. 3% and 53. 3%,respectively. Endoscopic examination was performed in 25 patients before treatment and at the end of the 48th week. Eight of them achieved mucosal healing that was kept to the end of 96th week （8/8）.Whereas only 9 out of 17 patients without mucosal healing achieved CR at the end of 96th week （9/17,P=0. 026）. The clinical features were compared between CR group and non-CR group at the end of 48th week. Logistic regression analysis showed that regaining of hs-CRP was the only independent factor for maintaining remission by AZA treatment （ P= 0. 009,OR 10.1,95 % CI 1.8 ～ 57.9）. Sixteen patients （26.7 % ） had adverse events. Ten （16.7 % ） of them had to halt treatment because of serious adverse events. Leucopenia was the most common adverse event and could be occurred at any time during the treatment. Conclusion AZA combined with steroid therapy can effectively induce remission of active CD. Long term steroid-free remission is also effectively maintained by AZA treatment. The most common adverse event is leucopenia and some patients can get mucosal healing. Those who get mucosal healing may have longer duration of remission.