Aburumman, Razan

ABSTRACT 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.

ABSTRACT Introduction Patients with primary sclerosing cholangitis (PSC) and concomitant inflammatory bowel disease (IBD) are at increased risk of colorectal cancer (CRC). However, the risk of CRC in patients with PSC without IBD remains uncertain. We aimed to evaluate the risk of CRC in patients with PSC without a history of IBD using a large national database. Methods We conducted a retrospective cohort study using the TriNetX database to identify patients ≥ 18 years with PSC. Patients were then divided into two groups, PSC with IBD (PSC‐IBD cohort) and PSC without IBD (PSC non‐IBD cohort), and were matched with patients without a history of PSC or IBD (non‐PSC/non‐IBD group) by using 1:1 propensity score matching. The primary outcome was the risk of first diagnosis of CRC. With censoring applied, Kaplan–Meier analysis with hazard ratios (HRs) and 95% CIs was used to compare time‐to‐event rates at daily time intervals. Results PSC patients without IBD were at increased risk of CRC compared to the non‐PSC/IBD cohort (aHR = 2.91; 95% CI: 1.6–6.0). Patients with PSC and IBD exhibited a higher risk of CRC (aHR = 6.5; 95% CI: 3.78–11.2), especially among the UC cohort (aHR = 6.3; 95% CI: 3.2–12.4). Patients with PSC were at increased risk of various gastrointestinal malignancies (aHR = 10.5; 95% CI: 7.3–15; p < 0.0001), including hepatobiliary cancers, pancreatic cancer, and hepatocellular carcinoma. Discussion Our findings provide real‐world evidence that PSC is an independent risk factor for colorectal cancer, even in the absence of concomitant IBD. These results support the need for further research to determine whether patients with isolated PSC may benefit from tailored CRC surveillance strategies.

Abstract Patients with Crohn’s disease (CD) who undergo terminal ileum (TI) resection experience altered bile acid absorption, which may influence colorectal cancer (CRC) risk. We conducted a propensity-matched cohort study using TriNetX to compare CRC risk in patients with CD who underwent TI resection versus those who did not. Terminal ileum resection was associated with an increased risk of CRC (aHR = 2.58, 95% CI, 1.72–3.86). Patients with TI resection also had higher odds of colorectal polyps. These findings suggest the need for heightened CRC surveillance in patients with CD undergoing TI resection.

ABSTRACTIL‐17 inhibitors effectively treat psoriasis and psoriatic arthritis but may increase the risk of inflammatory bowel disease (IBD). We assessed their association with IBD compared to apremilast. Utilising the TriNetX database, we analysed patients with psoriasis or ankylosing spondylitis initiating IL‐17 inhibitors or apremilast. We used propensity score matching and Cox models to estimate IBD risk. Among 13,216 matched patients per group, 142 developed IBD with IL‐17 inhibitors versus 60 with apremilast (aHR = 2.50, 95% CI: 1.85–3.39). IL‐17 inhibitors increase IBD risk, necessitating careful patient selection and monitoring.