New-onset inflammatory bowel disease associated with immune checkpoint inhibitor therapy: A real-world multicenter analysis.

Abstract

11141 Background: Immune checkpoint inhibitors (ICIs) are increasingly used across a broad range of malignancies and are known to cause immune-mediated gastrointestinal toxicity. While acute colitis is a recognized adverse effect, the potential for ICIs to trigger de novo inflammatory bowel disease (IBD), a chronic immune-mediated condition with long-term treatment implications, has not been well studied, as ICIs enhance immune activation in ways that may also affect normal intestinal immune balance. With the expanding use of ICIs across cancer types and earlier lines of therapy, we examined the association between ICI exposure and the risk of developing incident IBD compared with chemotherapy. Methods: We conducted a retrospective cohort study using the TriNetX global federated research network, including adults (≥18 years) diagnosed with malignancy between 2020 and 2024. Patients with pre-existing Crohn’s disease, ulcerative colitis, or prior IBD-directed biologic or targeted therapy were excluded. Two cohorts were defined: patients treated with PD-1/PD-L1 or CTLA-4 inhibitors and patients treated with chemotherapy without ICI exposure. Propensity score matching (1:1) was performed to balance demographics, cancer type, and comorbidities, yielding 63,190 patients per cohort. Outcomes assessed within 365 days included incident IBD diagnoses, initiation of first-line IBD therapies, and escalation to biologic or targeted IBD agents. Risk estimates, hazard ratios (HRs), and Kaplan–Meier analyses were performed. Results: After propensity score matching, baseline characteristics were well balanced between cohorts. The risk of developing incident IBD was significantly higher among ICI-treated patients compared with chemotherapy-treated patients (risk ratio [RR] 2.96, 95% CI 1.86–4.70). Time-to-event analysis demonstrated a significantly increased hazard of IBD following ICI exposure (HR 3.37, 95% CI 2.12–5.35; log-rank p < 0.001). Escalation to biologic or targeted IBD therapies was also more common in the ICI cohort (RR, 3.04; 95% CI, 1.90–4.87; HR, 3.46; 95% CI, 2.16–5.55). In contrast, initiation of first-line therapies (mesalamine or budesonide) did not differ significantly between groups (RR 0.97, 95% CI 0.93–1.01). Conclusions: Among cancer patients without pre-existing IBD, immune checkpoint inhibitor therapy was associated with a significantly increased risk of de novo IBD and a greater likelihood of requiring advanced IBD therapies compared with chemotherapy alone. These findings suggest that, in a subset of patients, immune checkpoint inhibition may be associated with the development of chronic intestinal immune disease, highlighting the need for increased awareness and longitudinal gastrointestinal monitoring as ICI use continues to expand.