Risk of Serious and Opportunistic Infections Associated With Treatment of Inflammatory Bowel Diseases
Risk of Serious and Opportunistic Infections Associated With Treatment of Inflammatory Bowel Diseases
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DOI：
10.1053/j.gastro.2018.04.012
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发表时间：
2018-08-01
期刊：
影响因子：
29.4
通讯作者：
Dray-Spira, Rosemary
中科院分区：
文献类型：
--
作者：
Kirchgesner, Julien;Lemaitre, Magali;Dray-Spira, Rosemary
背景与目的：与肿瘤坏死因子拮抗剂（抗TNF）和硫嘌呤（联合治疗）相关的感染风险尚不确定。我们在法国的一个大型队列中评估了接受硫嘌呤单药治疗、抗TNF单药治疗或联合治疗的炎症性肠病（IBD）患者发生严重和机会性感染的风险。方法：采用正交设计法我们对法国国家健康保险数据库中诊断为IBD的患者（18岁或以上）进行了一项全国性的基于人群的研究;我们收集了2009年1月1日至2014年12月31日的数据。采用边际结构考克斯比例风险模型，根据基线和随时间变化的社会人口学特征、药物和合并症进行校正，比较与联合治疗、抗TNF和巯基嘌呤单药治疗相关的严重和机会性感染风险。结果：在我们分析的190，694例IBD患者中，发生了8561例严重感染和674例机会性感染。与抗TNF单药治疗相比，联合治疗与严重感染（风险比[HR]，1.23; 95%置信区间[CI]，1.05-1.45）和机会性感染（HR，1.96; 95% CI，1.32-2.91）的风险增加相关。与硫嘌呤单药治疗相比，抗TNF单药治疗与严重感染（HR，1.71; 95%CI，1.56-1.88）、分支杆菌感染（HR，1.98; 95%CI，1.15-3.40）和细菌感染（HR，2.38; 95%CI，1.23-4.58）的风险增加相关。相反，与巯嘌呤单药治疗相比，抗TNF单药治疗与机会性病毒感染风险降低相关（HR，0.57; 95% CI，0.38-0.87）。结论：在法国IBD患者的全国性队列研究中，我们发现接受免疫抑制方案治疗的患者发生严重和机会性感染的风险存在异质性。应仔细考虑这些因素，并与IBD治疗在患者管理中的潜在获益进行权衡。
BACKGROUND & AIMS: The risk of infection associated with tumor necrosis factor antagonists (anti-TNF) and thiopurines (combination therapy) is uncertain. We assessed the risk of serious and opportunistic infections in patients with inflammatory bowel disease (IBD) treated with thiopurine monotherapy, anti-TNF monotherapy, or combination therapy in a large cohort of patients in France. METHODS: We performed a nationwide population-based study of patients (18 years or older) with a diagnosis of IBD in the French national health insurance database; we collected data from January 1, 2009 until December 31, 2014. The risks of serious and opportunistic infections associated with exposure to combination therapy, anti-TNF, and thiopurine monotherapies were compared using marginal structural Cox proportional hazard models adjusted for baseline and time-varying sociodemographic characteristics, medications, and comorbidities. RESULTS: Among the 190,694 patients with IBD included in our analysis, 8561 serious infections and 674 opportunistic infections occurred. Compared with anti-TNF monotherapy, combination therapy was associated with increased risks of serious infection (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.05-1.45) and opportunistic infection (HR, 1.96; 95% CI, 1.32-2.91). Compared with thiopurine monotherapy, anti-TNF monotherapy was associated with increased risks of serious infection (HR, 1.71; 95% CI, 1.56-1.88), mycobacterial infection (HR, 1.98; 95% CI, 1.15-3.40), and bacterial infection (HR, 2.38; 95% CI, 1.23-4.58, respectively). Conversely, anti-TNF monotherapy was associated with decreased risk of opportunistic viral infection compared with thiopurine monotherapy (HR, 0.57; 95% CI, 0.38-0.87). CONCLUSIONS: In a nationwide cohort study of patients with IBD in France, we found heterogeneity in risks of serious and opportunistic infections in patients treated with immune-suppressive regimens. These should be carefully considered and weighed against potential benefits for IBD treatment in patient management.