S3083 Immune Checkpoint Inhibitors and the Risk of Celiac Disease: A Propensity Score-Matched Analysis

Introduction: Immune checkpoint inhibitors (ICIs) are increasingly used to treat advanced malignancies but are associated with immune-related adverse events (irAEs), particularly gastrointestinal complications. While ICI-related colitis is well documented, the risk of developing celiac disease (CeD), an immune-mediated enteropathy, remains unclear. Methods: We conducted a retrospective cohort study using a large, de-identified electronic health record database (TriNetX). Adult patients with malignant neoplasms (International Classification of Diseases-10: C00–C96) were included. The ICI group received atezolizumab, nivolumab, durvalumab, ipilimumab, or pembrolizumab; the non-ICI group had no exposure to these agents. Patients with pre-existing CeD were excluded. Propensity score matching (1:1) was performed based on age, sex, and cancer type, yielding 2 matched cohorts (n = 124,205 each). The primary outcome was new-onset CeD (International Classification of Diseases-10: K90.0) within 2 years of cancer diagnosis and ICI initiation. Results: In the matched analysis, CeD developed in 125 patients treated with ICIs (0.10%) versus 69 patients in the non-ICI group (0.06%). This corresponds to a risk ratio of 1.81 (95% CI: 1.35–2.43, P < 0.001). While the average number of CeD-related encounters was higher in the ICI group (mean 4.1 vs 3.1), this difference did not reach statistical significance (P = 0.285). The findings suggest that ICIs are associated with nearly double the risk of developing CeD compared to patients not exposed to these agents. Conclusion: Our results highlight a potential new immune-related adverse event associated with ICIs—celiac disease. Although rare, CeD may be under-recognized in this setting. Oncologists and gastroenterologists should consider CeD in patients presenting with persistent mild diarrhea, weight loss, or nutritional deficiencies while on ICIs. Further prospective studies are needed to understand the mechanisms and develop appropriate screening strategies.