英夫利西单克隆抗体治疗486例克罗恩病的不良反应分析

Analysis of adverse effects of infliximab treatment in 486 patients with Crohn′s disease

目的评估CD患者应用英夫利西单克隆抗体(IFX)治疗的安全性。方法纳入2009年1月至2018年5月浙江大学医学院附属邵逸夫医院IBD中心486例使用IFX治疗的CD患者,收集其临床资料。统计学方法采用单因素及多因素logistic二元回归分析。结果随访中位时间为31.1个月(12.0个月,40.0个月),IFX中位疗程为13.0个月(7.0个月,21.0个月)。486例患者中,98例(20.16%)发生不良反应;因不良反应停药者12例(2.47%)。急性输液反应为CD患者使用IFX的最常见不良反应,发生率为8.44%,占所有不良反应的41.84%(41/98), 39例为轻、中度,均在对症处理后好转(其中8例因输液反应反复发生而停药)。严重的急性输液反应仅2例,表现为过敏性休克,抢救后好转。4例患者出现迟发过敏反应。486例患者中,感染39例(8.02%),存在难辨梭状芽孢杆菌、巨细胞病毒、带状疱疹病毒和结核分枝杆菌等机会性致病病原体感染,无感染相关的死亡病例,36例患者在感染控制后可继续行IFX治疗。486例患者中,重症感染14例(2.88%),均经抗感染治疗后好转。27例合并慢性HBV感染者均予抗病毒治疗,未见活动期HBV感染。1例患者在停用IFX 22个月后肠镜检查发现结肠腺癌;6例合并良性肿瘤病史患者用药期间无肿瘤复发、进展或恶变证据。在486例患者中,其他少见不良反应有肝功能异常8例(1.64%),贫血2例(0.41%),周围神经病变1例(0.21%),皮肤病变4例(0.82%)。IFX疗程延长、不合用免疫抑制剂和基线BMI升高是发生急性输液反应的危险因素;IFX疗程延长、基线白蛋白低于正常水平是发生感染的危险因素。结论CD患者应用IFX治疗总体安全,不良反应临床可控。用药前筛查和用药时监测可降低不良反应发生风险。

Objective To assess the safety of infliximab(IFX) treatment in patients with Crohn′s disease(CD). Methods From January 2009 to May 2018, at inflammatory bowel disease (IBD) center of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 486 CD patients received the treatment of IFX were enrolled and their clinical data were collected. Univariate and multivariate regression of binary logistic were performed for statistical analysis. Results The median follow-up duration was 31.1 months (12.0 months to 40.0 months). The median duration of IFX therapy was 13.0 months (7.0 months to 21.0 months). Among 486 patients, 98 (20.16%) patients reported adverse effects, and 12 (2.47%) patients discontinued the therapy because of adverse effects. Acute infusion reaction was the most common adverse effect in CD patients who received IFX treatment accounting for 41.84%(41/98)of all the adverse effects, and the incidence was 8.44%. Thirty-nine patients had mild and moderate infusion reaction, and all improved after symptomatic treatment (eight patients discontinued IFX therapy because of recurrent infusion reaction). Two patients developed severe infusion reaction as allergic shock, and both relieved after emergency rescue. Four patients developed late-phase allergic reactions. Among 486 patients, 39 (8.02%) patients had infections, including infections of Clostridium difficile, cytomegalovirus, herpeszoster virus, Mycobacterium tuberculosis, and other opportunistic pathogens. There was no cases of infection related death. Thirty-six patients continued with IFX treatment after infection controlled. Among 486 patients, 14(2.88%) patients had severe infection, and all the cases improved after anti-infection treatment. Twenty-seven CD patients with hepatitis B virus (HBV) infection received anti-viral treatments, no active HBV infection was observed. Colon adenocarcinoma was found in one patient under colonoscopy at 22 months after discontinuation of IFX therapy. There were six patients with the history of benign tumors, and no evidence of recurrence, progress or malignancy during treatment. In terms of other rare adverse effects in 486 patients, there were eight (1.64%) patients with liver function injury, two (0.41%) patients with anemia, one (0.21%) patient with peripheral neuropathy, and four (0.82%) patients with skin lesion. Prolonged duration of IFX therapy, without combination of immune-suppressors and with increased baseline body mass index (BMI) were the risk factors of acute infusion reactions. Prolonged duration of IFX therapy and with low baseline albumin level were the risk factors of infections. Conclusions IFX is generally safe as the treatment for CD patients, and its adverse effects can be clinically controlled. Screening before therapy and monitoring during therapy may reduce the risks of adverse effects.