Cumulative Incidence and Risk Factors for Advanced Neoplasia following Inflammatory Bowel Disease-Related Low-Grade Dysplasia: A Danish Nationwide Cohort Study

Background Individuals with inflammatory bowel disease (IBD) and related low-grade dysplasia (LGD) have an elevated risk of developing high-grade dysplasia (HGD) or colorectal cancer (CRC). The magnitude of this risk and the influence of risk factors, such as the calendar year of diagnosis and exposure to medical therapy, remain uncertain. We therefore investigated the 15-year cumulative incidence of HGD or CRC and the impact of potential risk factors using Danish healthcare registers. Methods We conducted a nationwide cohort study of all Danish individuals diagnosed with IBD-related LGD between 1997 and 2023. Individuals with prior colectomy, HGD, CRC, or familial adenomatous polyposis were excluded. The cumulative incidence of subsequent HGD or CRC was estimated, treating death and colectomy as competing risks. Multivariable cox regression assessed hazard ratios (HRs) for potential risk factors. Results Among 7,455 individuals, the 15-year cumulative incidence of HGD and/or CRC following IBD-related LGD was 6.3% (95% confidence interval CI 5.5–7.2). The risk declined over time, with lower hazards in 2017–2020 (HR 0.45 [95% CI 0.30–0.67]) and 2020–2023 (HR 0.24 [95% CI 0.14–0.43]) compared with 1997–2010. Anti-TNF-α therapy (≥5 doses) showed a non-significant trend towards reduced risk (HR 0.32 [95% CI 0.09–1.11]). Identified risk factors included: age (per 5 years: HR 1.11 [95% CI 1.06–1.17]), IBD duration (per 5 years: HR 1.13 [95% CI 1.07–1.19]), having a first-degree relative with colorectal cancer (HR 1.73 [95% CI 1.12–2.68]), episodes of elevated faecal calprotectin (per episode in the 5 years prior to inclusion: HR 1.14 [95% CI 1.02–1.27]), and high-dose prednisone use in the year prior to inclusion (HR 1.53 [95% CI 1.01–2.31]). Conclusion Among Danish individuals with IBD-related LGD, the overall 15-year cumulative incidence of subsequent HGD or CRC was 6.3% and has declined markedly over time. In addition to established risk factors, including age, IBD duration, family history of colorectal cancer, and elevated faecal calprotectin, we found that high-dose prednisone use was associated with an increased risk.