Background Anti-integrin αvβ6 immunoglobulin G autoantibodies have emerged as one of the most accurate non-invasive biomarkers for ulcerative colitis (UC). We aimed to validate their diagnostic performance in a French multicentre cohort of patients with inflammatory bowel disease (IBD) and to evaluate their predictive value for vedolizumab clinical response.Methods We performed a multicentre, non-interventional post hoc analysis using prospectively collected serum samples and clinical data from two parent prospective observational studies: VEDOPREDIRESP (patients with IBD initiating vedolizumab) and GOLILOR (patients with UC undergoing golimumab dose intensification). Serum anti-αvβ6 autoantibody titres were quantified by ELISA at baseline and week 6 (VEDOPREDIRESP) or week 8 (GOLILOR), blinded to clinical outcomes. The primary endpoint was sustained clinical remission at week 52.Results In the VEDOPREDIRESP cohort (n=115; 67 UC, 48 Crohn’s disease (CD), sustained clinical remission at week 52 was achieved in 54% of patients with UC. Baseline serum anti-αvβ6 autoantibody titres were significantly higher in UC than in CD (median 271 ng/mL (IQR 38–884) vs 5.2 ng/mL (2.5–10), p<0.001), with seropositivity (>9.1 ng/mL) in 94% vs 19%, respectively. Receiver operating characteristic (ROC) analysis confirmed excellent diagnostic performance to discriminate between UC and CD (area under the ROC curve (AUC) 0.93; optimal cut-off 15 ng/mL; sensitivity 92%, specificity 95%). In patients with UC treated with vedolizumab, titres declined significantly from baseline to week 6 (median 243 ng/mL (176–884) to 190 ng/mL (89–320), p=0.040). A >30% reduction at week 6 strongly predicted sustained remission at week 52 (AUC 0.79; sensitivity 78%, specificity 80%). Multivariable analysis identified this early decline as the only statistically significant independent predictor of 1-year remission (adjusted OR 5.36, 95% CI 1.12 to 8.54, p=0.040). Notably, in an independent cohort of 47 patients with UC undergoing golimumab dose intensification, there was no reduction in median serum anti-αvβ6 autoantibody levels, with levels remaining stable from 197 ng/mL at week 0 to 205 ng/mL (97–457) at week 8 (p=0.730).Conclusions Anti-αvβ6 autoantibodies robustly discriminate UC from CD. In patients with UC treated with vedolizumab, their early and selective decline predicts clinical remission at 1 year and provides a precision tool to optimise gut-selective therapy in real time.
Interleukin (IL)-23 inhibition is now an established therapeutic strategy in inflammatory bowel disease (IBD), supported by the efficacy of selective IL-23p19 monoclonal antibodies in both Crohn’s disease (CD) and ulcerative colitis (UC). Advances in peptide engineering have also enabled direct oral targeting of the IL-23 receptor (IL-23R), introducing an alternative approach to inhibition of the same inflammatory pathway. This narrative review examines the biological rationale for targeting the IL-23–IL-23R axis and the clinical evidence establishing selective IL-23p19 inhibition in IBD. Particular attention is given to the clinical development of icotrokinra, an oral macrocyclic peptide IL-23R antagonist. Phase 3 studies in psoriasis have established the efficacy of oral IL-23R antagonism, while the phase 2b ANTHEM-UC study has provided clinical evidence of efficacy in IBD, with improvements in clinical and endoscopic outcomes accompanied by translational evidence of pathway suppression. Ongoing phase 3 programmes in UC and CD will determine whether oral IL-23R antagonism can achieve durable clinical and endoscopic efficacy and establish its place alongside existing IL-23p19 monoclonal antibodies. If successful, this approach could represent a broader shift towards highly selective oral targeting of extracellular inflammatory pathways that have traditionally required biological therapy.
Background Venous thromboembolism (VTE) is a major cause of preventable in-hospital mortality, yet disease-specific risk profiles remain poorly defined. In pancreatitis, one of the most common gastrointestinal causes of hospitalisation, thromboembolic complications are under-recognised, with limited data, especially on extrasplanchnic events. Evidence guiding screening and management remains scarce. We analysed VTE events in a large prospective cohort of patients with acute and chronic pancreatitis and derived a simple admission-time clinical risk score to support early identification of high-risk individuals.Methods We performed a retrospective analysis of a prospectively recruited cohort at LMU Klinikum Munich, a referral centre for pancreatic diseases. Patients with acute, acute-on-chronic or chronic pancreatitis evaluated between January 2018 and June 2023 were included. Comprehensive clinical, laboratory, imaging and outcome data were extracted. The primary objective was to identify admission-time factors associated with VTE and develop a clinically actionable risk score. Continuous variables were dichotomised using receiver operating characteristic (ROC)-derived optimal cut-points. Binary predictors were entered into a multivariable logistic regression model, and coefficients were scaled to generate an integer-based point score. Discrimination was assessed using the area under the ROC curve (AUC), and patients were stratified into low-risk, intermediate-risk and high-risk groups.Results Among 647 patients, 114 (17.6%) developed VTE, with similar incidence rates in acute (59, 16.2%) and chronic pancreatitis (55, 19.5%). Deep vein thrombosis (5.9%) and pulmonary embolism (4.2%) were the most frequent events. Patients with VTE experienced significantly worse clinical courses, including longer hospitalisation (15 vs 7 days, p<0.001), higher rates of severe pancreatitis and increased need for advanced analgesia. Thrombosis was associated with lower diastolic blood pressure, reduced oxygen saturation, tachycardia, older age and lower body mass index at admission as well as higher rates of systemic and local complications. Mortality was markedly higher in patients with VTE (8.8% vs 2.1%, p=0.029). A six-item admission-only risk score (0–8 points) demonstrated good discrimination (AUC 0.71) and effectively stratified patients into low-risk (7.6%), intermediate-risk (22.0%) and high-risk groups (38.5%).Conclusion VTE is common in pancreatitis and strongly associated with adverse outcomes. A simple admission-time clinical score reliably identifies high-risk patients and may support earlier recognition, targeted diagnostic evaluation and risk stratification.
Background Imaging features play a central role in hepatocellular carcinoma (HCC) staging, but current systems remain limited in prognostic precision and treatment guidance. Pathological gross classification, which categorises HCC into four subtypes based on tumour margin morphology, represents a morphological surrogate of aggressive tumour behaviour encompassing histological and molecular features and has demonstrated value in predicting prognosis and guiding adjuvant locoregional therapy selection. Importantly, gross classification is assessable through imaging, but its evaluation utterly depends on postoperative pathology and remains subjective, time-consuming and poorly reproducible. We aimed to develop a three-dimensional (3D) Foundation Model-driven system to automatically perform non-invasive morphological phenotyping and to evaluate its prognostic utility.Methods A cohort of 551 patients who underwent hepatectomy after gadoxetic acid-enhanced MRI from two medical centres was retrospectively analysed. Pathological gross classification served as the reference standard. The 3D MorphStratify Model was built to automatically phenotype 3D gross classification with a dedicated 3D Foundation Model encoder and a channel-aware fusion module. A combined model integrating 3D MorphStratify and Conventional Imaging Predictors (Morph-CIP) was constructed and validated for recurrence risk stratification. The biological rationale linking imaging morphological phenotyping to underlying biology was preliminarily explored.Results Eligible patients were divided into a development dataset (n=291), a validation dataset (n=192) and an external test set (n=68). The 3D MorphStratify Model achieved a micro-averaged area under the receiver operating characteristic curve (AUC) of 0.932, significantly outperforming senior radiologists (AUC 0.825) with about 40-fold improved efficiency. The imaging-based 3D morphological phenotyping (3D MorphStratify) independently predicted poor recurrence-free survival (RFS, HR 2.16, 95% CI 1.20 to 3.87, p=0.010). The Morph-CIP Model enables risk stratification through training set (AUC 0.836, 0.768, 0.765 for 1-year, 2-year, 3-year RFS), internal test set (AUC 0.816, 0.690, 0.711) and external test set (AUC 0.737, 0.709, 0.702). The high-risk group is characterised by the enrichment of glycolysis and hypoxia signalling pathways.Conclusion 3D MorphStratify is the first automated 3D morphological phenotyping system for HCC, transforming subjective pathological gross classification into an objective, non-invasive imaging biomarker. The integration of 3D MorphStratify with conventional imaging predictors enables recurrence risk stratification, potentially providing complementary information for prognostic evaluation.
