Kim Hee Man, Kim Jin Woo, Kim Hyun-Soo, Kim Joo Sung, Kim You Sun, Cheon Jae Hee, Kim Won Ho, Ye Byong Duk, Moon Won, Jung Sung Hee, Kim Young-Ho, Han Dong Soo
Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Korea.
Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
J Clin Med. 2020 Dec 23;10(1):25. doi: 10.3390/jcm10010025.
The incidence of Crohn's disease and the number of associated surgeries are increasing in Korea. This study investigated the effect of azathioprine/6-mercaptopurine (6-MP) and TNF-α antagonists on abdominal and perianal surgery in Korean patients with Crohn's disease. A retrospective cohort study. Data from the Crohn's Disease Clinical Network and Cohort (CONNECT) were used. Patients with confirmed Crohn's disease between 1982 and 2008 from 32 hospitals in the Republic of Korea were enrolled. The effect of azathioprine/6-MP on abdominal and perianal surgery was analysed using logistic regression analysis adjusting for age and sex. In total, 1161 Crohn's disease patients were included in the Republic of Korea in the surgery ( = 462, male = 339, female = 123) and control groups ( = 699, male = 484, female = 215). In total, 1161 patients were selected, with 462 patients who underwent abdominal ( = 245) or perianal surgery ( = 217). The preoperative usage rates of azathioprine/6-MP were 18.8% and 65.1% ( < 0.0001) in the surgery and control groups, respectively. The preoperative usage rates of TNF-α antagonists were 7.1% and 23.3% ( < 0.0001) in the surgery and control groups, respectively. A multivariate analysis revealed that the preoperative use of azathioprine/6-MP had an odds ratio of 0.094 for all surgeries (95% confidence interval [CI]: 0.070-0.127, < 0.0001), 0.131 for abdominal surgery (95% CI: 397-1.599, < 0.0001), and 0.059 for perianal surgery (95% CI: 0.038-0.091, < 0.0001). The preoperative use of TNF-α antagonists had an odds ratio of 0.225 for all surgeries (95% CI: 0.151-0.335, < 0.0001), 0.403 for abdominal surgery (95% CI: 0.261-0.623, < 0.0001), and 0.064 for perianal surgery (95% CI: 0.026-0.160, < 0.001). The study presents new evidence of the reduced risk of surgery following azathioprine use in Crohn's disease patients. (1) This was not a controlled prospective study. (2) There was a selection bias specific to the CONNECT cohort. (3) The combination or sequential use of azathioprine/6-MP and TNF-α antagonists was not excluded. Azathioprine/6-MP is significantly associated with a reduced risk of abdominal and perianal surgery in Korean patients with Crohn's disease.
在韩国，克罗恩病的发病率及相关手术数量呈上升趋势。本研究调查了硫唑嘌呤/6-巯基嘌呤（6-MP）和肿瘤坏死因子-α（TNF-α）拮抗剂对韩国克罗恩病患者腹部及肛周手术的影响。这是一项回顾性队列研究。研究使用了来自克罗恩病临床网络与队列（CONNECT）的数据。纳入了1982年至2008年间韩国32家医院确诊为克罗恩病的患者。采用逻辑回归分析，对年龄和性别进行校正，分析硫唑嘌呤/6-MP对腹部及肛周手术的影响。韩国共有1161例克罗恩病患者纳入手术组（n = 462，男性 = 339，女性 = 123）和对照组（n = 699，男性 = 484，女性 = 215）。共选取1161例患者，其中462例接受了腹部手术（n = 245）或肛周手术（n = 217）。手术组和对照组硫唑嘌呤/6-MP的术前使用率分别为18.8%和65.1%（P < 0.0001）。手术组和对照组TNF-α拮抗剂的术前使用率分别为7.1%和23.3%（P < 0.0001）。多因素分析显示，术前使用硫唑嘌呤/6-MP对所有手术的比值比为0.094（95%置信区间[CI]：0.070 - 0.127，P < 0.0001），对腹部手术为0.131（95% CI：0.0397 - 1.599，P < 0.0001），对肛周手术为0.059（95% CI：0.038 - 0.091，P < 0.0001）。术前使用TNF-α拮抗剂对所有手术的比值比为0.225（95% CI：0.151 - 0.335，P < 0.0001），对腹部手术为0.403（95% CI：0.261 - 0.623，P < 0.0001），对肛周手术为0.064（95% CI：0.026 - 0.160，P < 0.001）。该研究提供了新的证据，表明克罗恩病患者使用硫唑嘌呤后手术风险降低。（1）这不是一项对照前瞻性研究。（2）CONNECT队列存在特定的选择偏倚。（3）未排除硫唑嘌呤/6-MP与TNF-α拮抗剂的联合或序贯使用情况。硫唑嘌呤/6-MP与韩国克罗恩病患者腹部及肛周手术风险降低显著相关。
