接受生物制剂治疗的克罗恩病患者的结核病风险：日本医疗理赔数据库的回顾性分析
Tuberculosis risk in patients with Crohn's disease on biologics: a retrospective analysis of the Japanese Medical Claims Database.
作者信息
Fujimoto Koji, Hosomi Shuhei, Kobayashi Yumie, Nakata Rieko, Nishida Yu, Ominami Masaki, Nadatani Yuji, Fukunaga Shusei, Otani Koji, Tanaka Fumio, Ohfuji Satoko, Fujiwara Yasuhiro
机构信息
Department of Gastroenterology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Department of Gastroenterology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.
出版信息
Intest Res. 2025 Jul;23(3):309-317. doi: 10.5217/ir.2024.00076. Epub 2024 Aug 19.
BACKGROUND/AIMS: Treatment using tumor necrosis factor-α (TNF-α) inhibitors is one of the risk factors for active tuberculosis (TB) in patients with Crohn's disease (CD). Biologics, such as ustekinumab (UST) and vedolizumab (VDZ), are less likely to cause opportunistic infections. However, large-scale studies for active TB and biologics other than TNF-α inhibitors are limited. We aimed to investigate the association between biologics and active TB utilizing a Japanese medical claims database.
METHODS
We analyzed retrospectively the association of the risk of active TB development with treatment using TNF-α inhibitors and other biologics (UST and VDZ) in patients with CD using the Japanese Medical Data Vision (MDV) database between April 2008 and June 2022. The durations of each biologic and biologic-free treatment were calculated for each patient. Univariate and multivariate analyses were performed using the Cox proportional hazards model, with the utilization of biologics considered as time-dependent covariates.
RESULTS
We included 28,811 patients with CD in MDV database. Finally, 17,169 patients were analyzed. In total, 7,064 patients were categorized as biologic-naïve, while 10,105 were classified as biologic-experienced. Seventeen patients developed active TB, including 7 on infliximab, 5 on adalimumab, and 5 on no biologics. None of the patients treated with UST and VDZ developed active TB. Multivariate analysis suggested that TNF-α inhibitors were the risk factors for active TB (hazard ratio, 3.66; P= 0.020).
CONCLUSIONS
TNF-α inhibitors, but not UST or VDZ, are risk factors for active TB in Japanese patients with CD.
背景/目的：使用肿瘤坏死因子-α（TNF-α）抑制剂进行治疗是克罗恩病（CD）患者发生活动性结核病（TB）的危险因素之一。乌司奴单抗（UST）和维多珠单抗（VDZ）等生物制剂引发机会性感染的可能性较小。然而，针对活动性结核病以及除TNF-α抑制剂之外的生物制剂的大规模研究较为有限。我们旨在利用日本医疗理赔数据库研究生物制剂与活动性结核病之间的关联。
方法
我们回顾性分析了2008年4月至2022年6月期间使用日本医疗数据视觉（MDV）数据库的CD患者中，使用TNF-α抑制剂及其他生物制剂（UST和VDZ）治疗与发生活动性结核病风险之间的关联。计算了每位患者使用每种生物制剂及未使用生物制剂治疗的时长。使用Cox比例风险模型进行单因素和多因素分析，将生物制剂的使用视为时间依赖性协变量。
结果
我们将MDV数据库中的28,811例CD患者纳入研究。最终，对17,169例患者进行了分析。其中，7,064例患者为未使用过生物制剂的初治患者，10,105例为使用过生物制剂的经治患者。17例患者发生了活动性结核病，其中7例使用英夫利昔单抗，5例使用阿达木单抗，5例未使用任何生物制剂。接受UST和VDZ治疗的患者均未发生活动性结核病。多因素分析表明，TNF-α抑制剂是活动性结核病的危险因素（风险比，3.66；P = 0.020）。
结论
在日本CD患者中，TNF-α抑制剂是活动性结核病的危险因素，而UST或VDZ不是。
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