Background: Both vedolizumab and ustekinumab are approved for the management of Crohn’s disease [CD]. Data on which one would be the most beneficial option when anti-tumour necrosis factor [anti-TNF] agents fail are limited. Aims: To compare the durability, effectiveness, and safety of vedolizumab and ustekinumab after anti-TNF failure or intolerance in CD. Methods: CD patients from the ENEIDA registry who received vedolizumab or ustekinumab after anti-TNF failure or intolerance were included. Durability and effectiveness were evaluated in both the short and the long term. Effectiveness was defined according to the Harvey–Bradshaw index [HBI]. The safety profile was compared between the two treatments. The propensity score was calculated by the inverse probability weighting method to balance confounder factors. Results: A total of 835 patients from 30 centres were included, 207 treated with vedolizumab and 628 with ustekinumab. Dose intensification was performed in 295 patients. Vedolizumab [vs ustekinumab] was associated with a higher risk of treatment discontinuation (hazard ratio [HR] 2.55, 95% confidence interval [CI]: 2.02–3.21), adjusted by corticosteroids at baseline [HR 1.27; 95% CI: 1.00–1.62], moderate–severe activity in HBI [HR 1.79; 95% CI: 1.20–2.48], and high levels of C-reactive protein at baseline [HR 1.06; 95% CI: 1.02–1.10]. The inverse probability weighting method confirmed these results. Clinical response, remission, and corticosteroid-free clinical remission were higher with ustekinumab than with vedolizumab. Both drugs had a low risk of adverse events with no differences between them. Conclusion: In CD patients who have failed anti-TNF agents, ustekinumab seems to be superior to vedolizumab in terms of durability and effectiveness in clinical practice. The safety profile is good and similar for both treatments.

Background: The Montreal classification has been widely used in Crohn's disease since 2005 to categorize patients by the age of onset (A), disease location (L), behavior (B), and upper gastrointestinal tract and perianal involvement. With evolving management paradigms in Crohn's disease, we aimed to assess the performance of gastroenterologists in applying the Montreal classification. Methods: An online survey was conducted among participants at an international educational conference on inflammatory bowel diseases. Participants classified 20 theoretical Crohn's disease cases using the Montreal classification. Agreement rates with the inflammatory bowel diseases board (three expert gastroenterologists whose consensus rating was considered the gold standard) were calculated for gastroenterologist specialists and fellows/specialists with ≤ 2 years of clinical experience. A majority vote < 75% among participants was considered a notable disagreement. The same cases were classified using three large language models (LLMs), ChatGPT‐4, Claude‐3, and Gemini‐1.5, and assessed for agreement with the board and gastroenterologists. Fleiss Kappa was used to assess within‐group agreement. Results: Thirty‐eight participants from five countries completed the survey. In defining the Montreal classification as a whole, specialists (21/38 [55%]) had a higher agreement rate with the board compared to fellows/young specialists (17/38 [45%]) (58% vs. 49%, p = 0.012) and to LLMs (58% vs. 18%, p < 0.001). Disease behavior classification was the most challenging, with 76% agreement among specialists and fellows/young specialists and 48% among LLMs compared to the inflammatory bowel diseases board. Regarding disease behavior, within‐group agreement was moderate (specialists: k = 0.522, fellows/young specialists: k = 0.532, LLMs: k = 0.577; p < 0.001 for all). Notable points of disagreement included: defining disease behavior concerning obstructive symptoms, assessing disease extent via video capsule endoscopy, and evaluating treatment‐related reversibility of the disease phenotype. Conclusions: There is significant inter‐rater disagreement in applying the Montreal classification, particularly for disease behavior in Crohn's disease. Improved education or revisions to phenotype criteria may be needed to enhance consensus on the Montreal classification.

Markers that allow for the selection of tailored treatments for individual patients with inflammatory bowel diseases (IBD) are yet to be identified. Our aim was to describe trends in real-life treatment usage. For this purpose, patients from the ENEIDA registry who received their first targeted IBD treatment (biologics or tofacitinib) between 2015 and 2021 were included. A subsequent analysis with Machine Learning models was performed. The study included 10,009 patients [71% with Crohn’s disease (CD) and 29% with ulcerative colitis (UC)]. In CD, anti-TNF (predominantly adalimumab) were the main agents in the 1st line of treatment (LoT), although their use declined over time. In UC, anti-TNF (mainly infliximab) use was predominant in 1st LoT, remaining stable over time. Ustekinumab and vedolizumab were the most prescribed drugs in 2nd and 3rd LoT in CD and UC, respectively. Overall, the use of biosimilars increased over time. Machine Learning failed to identify a model capable of predicting treatment patterns. In conclusion, drug positioning is different in CD and UC. Anti-TNF were the most used drugs in IBD 1st LoT, being adalimumab predominant in CD and infliximab in UC. Ustekinumab and vedolizumab have gained importance in CD and UC, respectively. The approval of biosimilars had a significant impact on treatment.

INTRODUCTION: Crohn's disease (CD) varies by location, potentially affecting therapy efficacy and surgery risk, although research on this topic is conflicting. This study aims to investigate the independent association between CD location and therapeutic patterns. METHODS: We analyzed patients with CD diagnosed from January 2005 to May 2023 registered in the nationwide ENEIDA registry. A univariate Cox regression analysis assessed the association of disease location with biologic use and persistence (with treatment discontinuation as a failure event), as well as the use of intestinal resections. A multivariate model was constructed to evaluate the independent association of disease location with therapeutic patterns, controlling for potential confounders such as sex, age at inclusion and diagnosis, disease duration and behavior, previous surgery or biological therapy, extraintestinal manifestations, and perianal disease. RESULTS: The study included 17,292 patients with a median follow-up period of 6 years (interquartile range 2–10 years). Ileocolonic location was associated with a higher biologic use than colonic location (hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.22–1.38) and ileal disease (HR 1.21, 95% CI 1.16–1.27), independently predicting biologic use (P < 0.001). Ileal location was associated with a lower biologic persistence than ileocolonic location (HR 1.14, 95% CI 1.07–1.21) and colonic disease (HR 1.10, 95% CI 1.01–1.20), independently predicting biologic persistence (P = 0.019). Ileal disease was associated with a higher likelihood of intestinal resections than colonic (HR 2.82, 95% CI 2.45–3.25) and ileocolonic location (HR 1.13, 95% CI 1.05–1.22), independently predicting the use of surgery (P < 0.001). DISCUSSION: CD location with ileal predominance is associated with a distinct therapeutic pattern, including higher biologic use, lower treatment persistence, and increased rates of intestinal resections.

Background: The diagnosis of coeliac disease (CD) in adults is based on clinical, serological and histological criteria. The inappropriate performance of intestinal biopsies, non-specificity of mild histological lesions and initiation of a gluten-free diet (GFD) before biopsy may hamper the diagnosis. In these situations, determining the intraepithelial lymphogram of the duodenum by flow cytometry (IEL-FC) can be helpful. Objectives: To describe the clinical scenarios in which the IEL-FC is used and its impact on the diagnosis of CD. Methods: All adult patients with suspected CD at three tertiary centres for whom the duodenal histology and IEL-FC were available were identified. Catassi and Fasano’s diagnostic criteria and changes to a CD diagnosis after the IEL-FCs were collected. Results: A total of 348 patients were included. The following indications for an IEL-FC formed part of the initial study for CD (38%): negative conventional work-up (32%), already on a GFD before duodenal biopsies (29%) and refractoriness to a GFD (2%). The IEL-FC facilitated a definitive diagnosis in 93% of patients with an uncertain diagnosis who had had a conventional work-up for CD or who were on a GFD before histology. Conclusions: The IEL-FC facilitates the confirmation or rejection of a diagnosis of CD in clinical scenarios in which a conventional work-up may be insufficient.