沙利度胺治疗难治性克罗恩病的长期疗效及安全性分析

Thalidomide in refractory Crohn′s disease:long-term efficacy and safety

目的分析沙利度胺治疗难治性克罗恩病的长期疗效及安全性。方法回顾性分析2005年9月至2018年7月中山大学附属第一医院炎症性肠病中心使用沙利度胺治疗的克罗恩病患者的长期疗效和药物不良反应。结果共纳入79例患者,其中69例持续用药超过6个月。68例患者可达到临床缓解,临床缓解时的中位用药时间为3个月(范围0.5~14个月)。对68例临床缓解的患者进行长期随访,中位随访时间为33.5个月(范围7~110个月),其中17例复发,累积维持缓解率在临床缓解后的12、24和60个月分别为88.6%(95%CI 80.6%~96.6%)、80.7%(95%CI 70.3%~91.1%)和53.7%(95%CI 32.1%~75.3%)。克罗恩病疾病活动指数(CDAI)是预测复发的独立风险因素,开始治疗时疾病处于中重度活动期(CDAI≥220分)的患者,日后复发风险是轻度活动患者的3.559倍(95%CI 1.213~10.449,P<0.05)。42例(53.2%)出现不良反应,12例(15.2%)因不良反应停药,未见严重的不良反应。结论沙利度胺能够有效维持成人克罗恩病的临床缓解,中重度患者复发风险增加。沙利度胺的不良反应发生率高,是限制其使用的主要原因。

Objective To analyze the long-term efficacy and safety of thalidomide on refractory Crohn′s disease(CD).Methods A total of 79 patients with refractory CD in the First Affiliated Hospital of Sun Yat-sen University treated with thalidomide were enrolled in this retrospective study from September 2005 to July 2018.Clinical effects and adverse drug reactions were recorded and assessed.Results In this cohort,69 patients were treated with thalidomide for≥6 months.Sixty-eight patients among the 69 patients achieved complete clinical remission and were followed up for a median 33.5 months(range,7-110 months).Seventeen cases relapsed during follow-up.The cumulative probabilities of remaining in remission at 12,24,60 months were 88.6%(95%CI 80.6%-96.6%),80.7%(95%CI 70.3%-91.1%),53.7%(95%CI 32.1%-75.3%)respectively.Disease activity was the only variable associated with relapse risk,with a hazard ratio(HR)of 3.559 for Crohn′s disease activity index(CDAI)≥220(95%CI 1.213-10.449,P<0.05).Adverse reactions were recorded in 42(53.2%)patients including12(15.2%)leading to discontinuation of thalidomide.No serious side effects were observed in all subjects.Conclusions This study suggests a long-term benefit of maintenance treatment with thalidomide in refractory CD.Moderate to severe patients have an increased risk of relapse.The high incidence of drug adverse reactions may restrain the clinical application of thalidomide.