Effect of Thiopurine on Potential Surgical Intervention in Crohn's Disease in Korea: Results from the CONNECT Study

Abstract

Objectives: The incidence of Crohn&apos;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-alpha antagonists on abdominal and perianal surgery in Korean patients with Crohn&apos;s disease. Design: A retrospective cohort study. Setting: Data from the Crohn&apos;s Disease Clinical Network and Cohort (CONNECT) were used. Patients with confirmed Crohn&apos;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. Participants: In total, 1161 Crohn&apos;s disease patients were included in the Republic of Korea in the surgery (n = 462, male = 339, female = 123) and control groups (n = 699, male = 484, female = 215). Results: In total, 1161 patients were selected, with 462 patients who underwent abdominal (n = 245) or perianal surgery (n = 217). The preoperative usage rates of azathioprine/6-MP were 18.8% and 65.1% (p < 0.0001) in the surgery and control groups, respectively. The preoperative usage rates of TNF-alpha antagonists were 7.1% and 23.3% (p < 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, p < 0.0001), 0.131 for abdominal surgery (95% CI: 397-1.599, p < 0.0001), and 0.059 for perianal surgery (95% CI: 0.038-0.091, p < 0.0001). The preoperative use of TNF-alpha antagonists had an odds ratio of 0.225 for all surgeries (95% CI: 0.151-0.335, p < 0.0001), 0.403 for abdominal surgery (95% CI: 0.261-0.623, p < 0.0001), and 0.064 for perianal surgery (95% CI: 0.026-0.160, p < 0.001). Strengths of this study: The study presents new evidence of the reduced risk of surgery following azathioprine use in Crohn&apos;s disease patients. Limitations of this study (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-alpha antagonists was not excluded. Conclusion: Azathioprine/6-MP is significantly associated with a reduced risk of abdominal and perianal surgery in Korean patients with Crohn&apos;s disease.