Risk of Coeliac Disease After Immune Checkpoint Inhibitor Exposure in Patients With Cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) enhance anti-tumour immunity by modulating immune pathways but can also trigger immune-related adverse events. We aimed to evaluate the risk of developing coeliac disease (CeD) among patients with malignancy treated with ICIs. METHODS: Using the TriNetX US Collaborative Network, we identified adults (≥ 18 years) diagnosed with malignancies for which ICIs are routinely used between January 2010 and December 2024 and stratified them by exposure to immune checkpoint inhibitors (nivolumab, pembrolizumab, ipilimumab, atezolizumab, durvalumab, tremelimumab, or avelumab). Patients with pre-existing celiac disease (CeD) were excluded. Cohorts were propensity score matched for demographics and autoimmune comorbidities. The primary outcome was incident CeD occurring ≥ 90 days after the index event. Adjusted hazard ratios (aHRs) were calculated, with subgroup analyses by age and sex. Statistical significance was defined as p < 0.05. RESULTS: After propensity score matching, 158,208 patients were included in each cohort. CeD was diagnosed more frequently among patients exposed to ICIs than among matched controls (0.152% vs. 0.071%; aHR 3.95, 95% CI 3.11-5.03; p < 0.001), corresponding to a number needed to harm (NNH) of 1235. The increased risk persisted across sex and age subgroups, including females (aHR 3.43, 95% CI 2.55-4.62), males (aHR 5.36, 95% CI 3.53-8.12), with the risk being highest among patients older than 60 years (0.14% vs. 0.06%; aHR 4.24, 95% CI 3.17-5.67; p < 0.001). CONCLUSION: In this large real-world cohort, ICI exposure was associated with nearly a fourfold increase in the risk of being diagnosed with CeD compared with matched controls.