Risk factors for immune checkpoint inhibitor colitis: a retrospective multi-center cohort study using electronic health records

Background Immune checkpoint inhibitors (ICIs) are effective for many cancers but often cause immune–related adverse events, particularly gastrointestinal (GI) complications such as colitis. Identifying risk factors for ICI colitis (CIC) could improve patient selection and discover potential mechanisms relevant to idiopathic inflammatory bowel disease (IBD). Prior studies on ICI risk factors have methodological limitations. Methods We used electronic health record data from six University of California institutions with 10,260 adults on ICIs. Baseline and time–varying predictors were defined based on prior IBD epidemiology studies, including interactions. LASSO Cox regression was applied to data from UCSF Central Data Warehouse to select the most predictive model, with coefficients estimated using multi–center data. Results and conclusion Fourteen significant predictors of CIC were identified. The strongest predictors were concurrent use of antibiotics (HR 2.72, 95% CI: 2.41–3.07) and non–steroid anti–inflammatory drugs (1.50, 1.16–1.94). Notable GI risk factors included gastroesophageal reflux disorder (1.31, 1.14–1.50), other GI disorders (1.32, 1.16–1.50), and disorders of the gallbladder, biliary tract, and pancreas (1.33, 1.15–1.57). High BMI before ICI administration increased risk (per unit 1.07, 1.04–1.09), while higher BMI after ICI administration decreased risk (per unit 0.93, 0.90–0.95). Melanoma, anxiety, and depression also increased risk. GI oncologists should consider ICI colitis in patients with comorbid GI disorders or those using antibiotics or NSAIDs. Baseline fecal calprotectin testing is recommended for these patients. Future studies are needed to explore the underlying mechanisms. Our findings suggest microbiome– and immune system–altering factors play roles in CIC and idiopathic GI disorders.