Background/Objectives: Vedolizumab (VDZ) is approved in the treatment of patients with moderate to severe ulcerative colitis (UC) or Crohn’s disease (CD). VDZ exhibits considerable variability in its pharmacokinetic (PK) profile, and its exposure-response relationship is not yet fully understood. The aim was to investigate the variability in VDZ trough levels and PK parameters, to assess the relationship between VDZ PK and biochemical response, as well as clinical and endoscopic outcomes. Methods: We included 61 UC and 45 CD patients. Patients’ data and trough VDZ concentrations were retrospectively obtained. Population PK analysis was performed using non-linear mixed-effects modelling with NONMEM (version 7.5). Graphs and statistical analyses were performed using R (version 4.1.3). Results: In total, 116 trough VDZ concentrations from 106 patients were described by a two-compartment model. For a typical patient, clearance (CL) was estimated at 0.159 L/day, while in patients previously treated with anti-TNFα agents, VDZ CL increased by 26.4% on average. In univariate binary logistic regression, VDZ trough concentration was not statistically significant predictor of remission, whereas CL was. Moreover, combined CL and faecal calprotectin (FCP) were a statistically significant predictors of remission. The hazard ratio (HR) for CL above 0.1886 L/day was 0.35 (p = 0.05) and for FCP below 250 µg/g was 2.66 (p = 0.02) in a time-to-event analysis. Conclusions: Our population PK model incorporates the effect of prior anti-TNFα agents on CL, suggesting its association with more severe forms of IBD. VDZ CL emerged as a more robust and clinically relevant predictor of remission in IBD patients than trough concentration.

Background/Objectives: Several population pharmacokinetic models of vedolizumab (VDZ) are available for inflammatory bowel disease (IBD) patients. However, their predictive performance in real-world clinical settings remains unknown. This study aims to externally evaluate the published VDZ pharmacokinetic models, focusing on their predictive performance and simulation-based clinical applicability. Methods: A literature search was conducted through PubMed to identify VDZ population pharmacokinetic models. A total of 114 VDZ concentrations from 106 IBD patients treated at the University Medical Center “Zvezdara”, Republic of Serbia, served as the external evaluation cohort. The predictive performance of the models was assessed using prediction- and simulation-based diagnostics. Furthermore, the models were utilized for Monte Carlo simulations to generate concentration–time profiles based on 24 covariate combinations specified within the models. Results: Four published pharmacokinetic models of VDZ were included in the evaluation. Using the external dataset, the median prediction error (MDPE) ranged from 13.82% to 25.57%, while the median absolute prediction error (MAPE) varied between 41.64% and 47.56%. None of the models fully met the combined criteria in the prediction-based diagnostics. However, in simulation-based diagnostics, pvcVPC showed satisfactory results, despite wide prediction intervals. Analysis of NPDE revealed that only the models by Rosario et al. and Okamoto et al. fulfilled the evaluation criteria. Simulation analysis further demonstrated that the median VDZ concentration remains above 12 μg/mL at week 22 during maintenance treatment for approximately 45–60% of patients with the best-case covariate combinations and an 8-week dosing frequency. Conclusions: None of the published models satisfied the combined criteria (MDPE, MAPE, percentages of prediction error within ±20% and ±30%), rendering them unsuitable for a priori predictions. However, two models demonstrated better suitability for simulation-based applications.

Inflammatory bowel disease is a recognized risk factor for venous thromboembolism, whereas arterial thrombotic events remain underappreciated despite their substantial clinical consequences. We report a 45-year-old man without significant comorbidities who developed severe ulcerative colitis complicated by diffuse arterial thrombosis, including cerebral infarctions, an ascending aortic mural thrombus, iliac artery thrombosis, and multi-organ infarctions. After stabilization with supportive care and anticoagulation, remission-directed ulcerative colitis therapy and a vascular safety–oriented maintenance strategy were initiated, including vedolizumab and individualized secondary thrombosis prevention. To contextualize this presentation, we integrate current evidence on the epidemiology, clinical phenotypes, underlying mechanisms, and risk factors for arterial thrombosis in inflammatory bowel disease, highlight disease activity as a dominant trigger, and summarize therapy-specific vascular safety considerations across IBD treatment classes.