S1795 Newer Biologics Show Lower Long-Term Cancer Risk Compared to TNF Inhibitors in Inflammatory Bowel Disease: A 5-Year Real-World Analysis

Introduction: Inflammatory bowel disease (IBD) is associated with chronic inflammation, increasing cancer risk through mechanisms such as DNA damage and cell proliferation. Biologic therapies, including tumor necrosis factor (TNF) inhibitors and newer biologics targeting alternative inflammatory pathways, play a pivotal role in IBD management. However, their long-term cancer risk remains a critical concern. This study evaluates the comparative cancer risk of TNF inhibitors vs newer biologics over 1, 3, and 5 years using real-world data. Methods: We analyzed cancer incidence in IBD patients (aged ≥18) treated with TNF inhibitors or newer biologics between January 2015 and December 2020 using the TriNetX database. Propensity score matching balanced demographic and clinical characteristics, creating 2 comparable cohorts (n = 20,354 each). We used Kaplan-Meier analysis and log-rank tests to calculate cancer-free probabilities and assess relative cancer risks through hazard ratios (HRs) and risk differences. Results: Newer biologics consistently demonstrated lower cancer risks compared to TNF inhibitors across all time points. At 1 year, cancer risk differences were similar (P = 0.074), but significant reductions emerged by 3 years (P = 0.026) and 5 years (P = 0.013). The 5-year cancer-free probability was higher for newer biologics (99.54%) compared to TNF inhibitors (99.20%, P = 0.007). Hazard ratios confirmed a persistent safety advantage for newer biologics, with a 5-year HR of 1.653 (95% CI: 1.143–2.391). Conclusion: Our study demonstrates that newer biologics provide a favorable long-term safety profile, with progressively lower cancer risks compared to TNF inhibitors. These findings highlight the importance of incorporating safety considerations into IBD treatment decisions, particularly for patients with heightened cancer risk. Future research should investigate the biological mechanisms underlying these differences and assess the broader clinical implications to optimize treatment strategies.