Association between tumour necrosis factor-α inhibitors and risk of serious infections in people with inflammatory bowel disease: nationwide Danish cohort study
Association between tumour necrosis factor-α inhibitors and risk of serious infections in people with inflammatory bowel disease: nationwide Danish cohort study
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DOI：
10.1136/bmj.h2809
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发表时间：
2015-06-05
影响因子：
105.7
通讯作者：
Jess, Tine
中科院分区：
文献类型：
--
作者：
Andersen, Nynne Nyboe;Pasternak, Bjorn;Jess, Tine
目的：研究炎症性肠病患者是否接受肿瘤坏死因子-α治疗（TNF-α）抑制剂增加了严重感染的风险。研究背景丹麦，2002- 12.参与者适合匹配的背景队列包括52392名患有炎症性肠病的人，年龄15 - 75岁，其中4300人接受了TNF-α抑制剂治疗。为了限制混杂因素，采用两阶段匹配方法;首先匹配年龄、性别、疾病持续时间和炎症性肠病亚型，其次匹配倾向评分（1：1比例）;这产生了1543名用TNF-α抑制剂治疗的人和1543名未治疗的人被包括在分析中。主要结果测量主要结果是任何严重的感染，定义为与入院相关的感染诊断。使用考克斯回归估计两个风险期（TNF-α抑制剂治疗开始后90天和365天）的风险比。仅在365天的风险期内获得了部位特异性严重感染的风险比。在90天的风险期内，在TNF-α抑制剂使用者中观察到51例感染病例（发病率14/100人年），而非吸毒者为33例（9/100人年），产生的风险比为1.63（95%置信区间1.01至2.63）。在365天的风险期内，风险比为1.27（0.92至1.75）。在部位特异性感染的分析中，几个亚组的风险比大于2，但仅皮肤和软组织感染达到统计学显著性（2.51，结论这项全国性倾向评分匹配队列研究表明，使用TNF-α可增加严重感染的风险。在开始治疗的前90天内使用α抑制剂，随后风险下降。这就需要提高对使用这些药物的炎症性肠病患者潜在感染并发症的临床认识，特别是在治疗过程的早期。
OBJECTIVETo investigate whether people with inflammatory bowel disease treated with tumour necrosis factor-alpha (TNF-alpha) inhibitors are at increased risk of serious infections.DESIGNNationwide register based propensity score matched cohort study.SETTINGDenmark, 2002-12.PARTICIPANTSThe background cohort eligible for matching comprised 52 392 people with inflammatory bowel disease, aged 15 to 75 years, of whom 4300 were treated with TNF-alpha inhibitors. To limit confounding, a two stage matching method was applied; firstly matching on age, sex, disease duration, and inflammatory bowel disease subtype, and secondly matching on propensity scores (1: 1 ratio); this yielded 1543 people treated with TNF-alpha inhibitors and 1543 untreated to be included in the analyses.MAINOUTCOME MEASURESThe main outcome was any serious infection, defined as a diagnosis of infection associated with hospital admission. Cox regression was used to estimate hazard ratios for two risk periods (90 and 365 days after the start of TNF-alpha inhibitor treatment). Hazard ratios of site specific serious infections were obtained solely for the 365 days risk period.RESULTSWithin the 90 days risk period, 51 cases of infection were observed in users of TNF-alpha inhibitors (incidence rate 14/100 person years), compared with 33 cases in non-users (9/100 person years), yielding a hazard ratio of 1.63 (95% confidence interval 1.01 to 2.63). Within the risk period of 365 days, the hazard ratio was 1.27 (0.92 to 1.75). In analyses of site specific infections, the hazard ratio was above 2 for several of the subgroups but only reached statistical significance for skin and soft tissue infections (2.51, 1.23 to 5.12).CONCLUSIONSThis nationwide propensity score matched cohort study suggests an increased risk of serious infections associated with use of TNF-alpha inhibitors within the first 90 days of starting treatment and a subsequent decline in risk. This calls for increased clinical awareness of potential infectious complications among people with inflammatory bowel disease using these drugs, especially early in the course of treatment.