P1197 Progression to colorectal cancer or high-grade dysplasia in individuals with inflammatory bowel disease and low-grade dysplasia: A cohort study of risk factors and incidence

Abstract Background Individuals with inflammatory bowel disease (IBD) face an increased risk for colorectal cancer (CRC) and high grade dysplasia (HGD) compared with individuals without IBD.1,2 Low-grade dysplasia (LGD) is recognized as a key risk factor for HGD and CRC development in IBD.3 However, the risk for progression from LGD to HGD or CRC is still debated. Studies report diverging results and are often limited by small sample sizes and selection bias.4 The influence of diagnosis-year and medications is particularly underexplored. Therefore, we sought to utilize the Danish healthcare registers to examine the impact of candidate risk factors for progression from LGD to either HGD or CRC among Danish individuals with IBD. Methods We conducted a cohort study, including all Danish individuals diagnosed with IBD and LGD between 1977 and 2022. IBD with LGD was defined as individuals with a LGD diagnosis up to 180 days before or any time after their first IBD diagnosis, using the latest date as index date. Individuals with a colectomy, HGD, or CRC before the index date were excluded. We investigated the cumulative incidence of progression to HGD or CRC, treating death as a competing risk. A univariate Cox regression model was used to assess hazard ratios (HRs) for potential risk factors. Variables with a P-value of ≤ 0.1 were included in the final multivariable cox regression model. Results We included 7,082 individuals with IBD and LGD for further analysis. As illustrated in figure 1 the cumulative incidence of progression from LGD to HGD or CRC at 15 years post-index was 6.70% (95% CI: 5.93–7.54). Several risk factors were identified (table 1). Of particular interest was the influence of index-year and treatment with prednisone and anti-TNF-α. In the final model, we observed a reduction in progression risk over time, with a decreased risk for progression in the period 2018-2021 (HR: 0.32 [95% CI: 0.21-0.50]) and 2015-2018 (HR: 0.53 [95% CI: 0.34-0.69]) relative to 1977-2010. High-dose prednisone treatment was associated with progression to HDG or CRC (HR: 1.77 [95% CI: 1.23-2.57]), whereas anti-TNF-α treatment was not (HR: 0.81 [95% CI:0.38–1.74]). Conclusion Among Danish individuals with IBD the risk of progression from LGD to HGD or CRC declined over time. Treatment with High-dose prednisone was associated with an increased risk of progression, whereas anti-TNF-α treatment was not. We speculate that recent advancements in biological treatments of IBD, the implementation of 'treat-to-target' strategies, and improved detection and resection of LGD lesions, may partly explain declining progression risk. References 1.Olén O, Erichsen R, Sachs MC, et al. Colorectal cancer in Crohn’s disease: a Scandinavian population-based cohort study. Lancet Gastroenterol Hepatol. 2020;5(5):475-484. doi:10.1016/S2468-1253(20)30005-4 2.Olén O, Erichsen R, Sachs MC, et al. Colorectal cancer in ulcerative colitis: a Scandinavian population-based cohort study. Lancet Lond Engl. 2020;395(10218):123-131. doi:10.1016/S0140-6736(19)32545-0 3.Fumery M, Dulai PS, Gupta S, et al. Incidence, Risk Factors, and Outcomes of Colorectal Cancer in Patients With Ulcerative Colitis With Low-Grade Dysplasia: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2017;15(5):665-674.e5. doi:10.1016/j.cgh.2016.11.025 4.De Jong ME, Van Tilburg SB, Nissen LHC, et al. Long-term Risk of Advanced Neoplasia After Colonic Low-grade Dysplasia in Patients With Inflammatory Bowel Disease: A Nationwide Cohort Study. J Crohns Colitis. 2019;13(12):1485-1491. doi:10.1093/ecco-jcc/jjz114