S416 When the Checkpoint Fails: ICI Colitis as a Pathway to Inflammatory Bowel Disease

Introduction: Immune checkpoint inhibitors (ICIs) are associated with gastrointestinal immune-related adverse events (irAEs), including colitis. While ICI colitis is typically considered transient, its potential to evolve into chronic inflammatory bowel disease (IBD) remains poorly characterized. We aimed to assess the incidence of IBD in ICI-treated melanoma patients and evaluate whether ICI colitis increases the risk of developing IBD. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, comprising electronic health record data from 142 healthcare organizations. Adult melanoma patients were divided into 2 cohorts: ICI-exposed (n = 33,537) and non-ICI controls (n = 2,017,847). Propensity score matching (1:1) yielded balanced groups (n = 6,745 each). Primary outcomes included new-onset IBD (ICD-10 K50–K52) and ICI colitis (T45.AX5 series). A separate subcohort of ICI-treated patients with ICI colitis (n = 6,786) was analyzed to assess IBD progression. Patients with prior IBD were excluded. Results: IBD occurred in 12.4% of ICI-treated patients versus 4.4% of controls (P < 0.001). ICI colitis occurred in 12.8% of ICI-treated patients and 0% of controls. Among the ICI colitis subcohort, 267 of 6,397 patients (4.2%) developed IBD after their initial colitis diagnosis, representing a clinically meaningful progression. Kaplan-Meier analysis showed significantly reduced IBD-free survival in patients with ICI colitis (P < 0.001). Conclusion: This large real-world study demonstrates that ICI therapy significantly increases the risk of both ICI colitis and de novo IBD in melanoma patients. Importantly, patients with ICI colitis had a higher risk of subsequent IBD, suggesting ICI colitis may unmask latent chronic inflammatory disease. These findings support the need for GI surveillance and early intervention in high-risk patients following ICI colitis.