早期应用英夫利昔单抗联合硫唑嘌呤治疗合并2个以上预后不良高危因素克罗恩病疗效及安全性研究

Efficiency and safety analysis of early application of Infliximab combined with azathiopurine in the treatment of Crohn's disease

目的探讨英夫利昔单抗(IFX)联合硫唑嘌呤(AZA)治疗合并2个以上预后不良高危因素克罗恩病(CD)患者的疗效及安全性。方法回顾性分析2013年3月至2015年6月中国医科大学附属盛京医院接受早期IFX联合AZA治疗的18例合并≥2个预后不良高危因素CD患者的临床资料。比较治疗前、治疗后14、30周患者实验室指标、克罗恩病活动指数(Best CDAI)评分、克罗恩病简化内镜评分(SES-CD)、瘘管愈合率及不良反应的情况。结果 18例患者均完成14周的治疗,其中9例完成30周的治疗。与治疗前相比,治疗后第14周患者Best CDAI、SES-CD评分、红细胞沉降率(ESR)及C反应蛋白(CRP)明显下降(P<0.05);红细胞比容(HCT)、白蛋白(ALB)及体重指数(BMI)明显升高(P<0.05)。与治疗后第14周相比,治疗后第30周患者Best CDAI、SES-CD评分进一步显著下降(P<0.05);BMI进一步上升(P<0.05)。第14、30周临床缓解率分别为83.3%(15/18)、88.9%(8/9);内镜下黏膜愈合率分别为11.1%(2/18)、55.6%(5/9)。6例合并有肛瘘的CD患者中2例完成第30周的治疗。治疗后第14周,6例瘘管部分愈合;2例患者完成了30周的治疗,瘘管均完全愈合。2例在第2周出现一过性肝功能异常,3例患者在第6周时出现WBC计数下降,经相应治疗短期内恢复正常,均未影响继续治疗。所有患者随访至2016年10月11日未观察到药物相关感染及恶性肿瘤等不良事件发生。结论 IFX早期联合AZA治疗合并≥2个预后不良高危因素的CD患者,可有效改善临床症状,控制全身炎症状态;持续治疗能够有效诱导并维持疾病缓解,促进内镜下肠黏膜愈合,促进瘘管愈合;且并未明显增加不良反应的发生。

Objective To explore the efficiency and safety of early application of IFX combined with AZA in the treatment of Crohn＇s disease with more than 2 poor prognostic factors. Methods Clinical data of 18 patients, who were diagnosed with CD with more than 2 poor prognostic factors and received early combined treatment oflFX and AZA from March 2013 to June 2015, was retrospectively analyzed.Laboratory indexes, Best-CDAI, SES-CD, rate of fistula closure and adverse effects were observed and compared before treatment and at 14th and 30th week after the beginning of treatment. Results Among the 18 CD patients,who have received 14 weeks of treatment, 9 received 30 weeks of treatment. Compared with that before treatment, at the 14th week the average BestCDM, SES-CD, ESR and CRP decreased obviously（P〈0.05）; Hct, ALB, BMI all rose （P〈0.05）.Compared with that at the 14th week, at the 30th week, the average BestCDAI and SES-CD continued to improve obviously（P〈0.05）; BMI further increased（P〈0.05）. The rates of clinical remission of the 14th and 30th week were 83.3% and 88.9%;the rates of endoscopic mucosal healing were 11.1% and 55.6%. Among the 6 CD patients who were complicated with fistula, 2 patients completed 30 weeks of treatment.At the time of 14th week, the rate of complete healing was 0, while the rate of partial healing was 100%.The fistulas of the two CD patients who had finished 30-week- treatment were healed.During the period of observation, 2 of the 18 patients had transient hepatic dysfunction in the 2nd week;3 had a drop of WBC count in the 6th week, but recovered soon after being given relative treatment without affecting further treatment.However, no adverse event of drug-related infection or malignancy has been observed during follow-up till now. Conclusion Early combined treatment of IFX and AZA can improve the clinical symptom and control whole body inflammory reaction of CD patients with more than 2 poor prognostic factorscontinuous treatment can induce and maintain the remission of disease efficientl）; promote the endo-copic healing of intestinal mucosa and the healing of fistulas.The incidence of adverse effect hasn＇t been increased significantly.