Yonsei Med J.  2021 Nov;62(11):997-1004. 10.3349/ymj.2021.62.11.997.

Medications and the Risk of Colorectal Cancer in Patients with Inflammatory Bowel Diseases: Use of the Landmark Method

• Choi YY
• Lee JK
• Kim HS
• Kim DW
• Kim HM
• Kang DR

• KMID: 2521450
• DOI: http://doi.org/10.3349/ymj.2021.62.11.997

Abstract

Purpose
This study aimed to determine whether the use of drugs in the treatment of inflammatory bowel disease is related to the risk of colorectal cancer using a Cox proportional hazards model with the landmark method to minimize immortal time bias.
Materials and Methods
This study was conducted as national cohort-based study using data from Korea’s Health Insurance Corporation. Newly diagnosed patients with inflammatory bowel disease from 2006 to 2010 were monitored for colorectal cancer until 2015. Hazard ratios and 95% confidence intervals were calculated and compared with the incidence of colorectal cancer with or without medications by applying various landmark points.
Results
In patients with Crohn’s disease, the prevention of colorectal cancer in the group exposed to immunomodulators was significant in the basic Cox model; however, the effect was not statistically significant in the model using the landmark method. The preventive effect of 5-aminosalicylic acid in patients with ulcerative colitis was significant in the basic and 6-month landmark point application models, but not in the remaining landmark application models.
Conclusion
In patients with inflammatory bowel disease, the preventive effect of drug exposure on colorectal cancer varies depending on the application of the landmark method. Hence, the possibility of immortal time bias should be considered.

Keyword

Bias; cohort study; colorectal cancer; inflammatory bowel disease; proportional hazards models; survival analysis