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Summary Background Aims Methods Results Conclusions Previous studies highlighted a more extensive phenotype for paediatric‐onset than adult‐onset inflammatory bowel disease (IBD). However, most lacked long‐term follow‐up, and some were conducted before the era of biologics.The aim of this study is to compare disease characteristics and treatment exposures between paediatric‐onset and adult‐onset IBD.From a registry that periodically and uniformly retrieves demographics, disease characteristics/phenotype, and treatments, we compared the characteristics of paediatric‐onset (diagnosed at ≥6 and <18 years) and adult‐onset IBD, diagnosed during 2000–2022 and with ≥12 months follow‐up.Of the 2837 patients with Crohn's disease and 1332 with ulcerative colitis, 3316 had adult‐onset and 853 paediatric‐onset IBD. The median follow‐up was 6 years. Patients with paediatric‐onset presented with more extensive disease and received more intensified therapies, including biologics and JAK inhibitors than those with adult‐onset IBD. Paediatric‐onset ulcerative colitis showed a higher prevalence of E3 extensive colitis including pancolitis and a greater requirement for systemic steroids, immunomodulators, and biologics than adult‐onset ulcerative colitis. Paediatric‐onset versus adult‐onset Crohn's disease exhibited greater L3 ileocolonic involvement and perianal disease phenotype, and higher exposure to immunomodulators and biologics. Kaplan–Meier curve and Cox proportional hazards analyses showed significantly lower 15‐year biologic‐free survival from diagnosis among those with paediatric‐onset IBD than with adult‐onset IBD (p = <0.001), indicating greater and earlier use of biologics in the former.Paediatric‐onset presents with more extensive disease with higher exposures to immunomodulators and biologic therapies than adult‐onset IBD. [ABSTRACT FROM AUTHOR]

Introduction: Complicated perianal disease (cPD) may be the sole presentation of Crohn's disease (CD). The role of small-bowel capsule endoscopy (SBCE) in the diagnostic algorithm of cPD is unclear. We aimed to evaluate the role of SBCE as a diagnostic tool, in patients with cPD, after a negative standard workup for CD. Methods: A multicenter, retrospective, cross-sectional study, in patients with cPD, and negative standard workup for CD (ileocolonoscopy and cross-sectional imaging), who underwent SBCE for suspected CD. Demographics, biomarkers, and the Lewis Score (LS) were recorded and analyzed. An LS ≥ 135 was considered a positive SBCE for diagnosing CD. Results: Ninety-one patients were included: 65 (71.4%) males; median age: 37 (29–51) years; cPD duration: 25.1 (12.5–66.1) months. Positive SBCE: 24/91 (26.4%) patients. Fecal calprotectin (FC) positively correlated with LS (r = 0.81; p < 0.001). FC levels of 100 µg/g and 50 µg/g had a sensitivity of only 40% and 55% to rule out small-bowel CD, with a negative predictive value (NPV) of only 76% and 80%, respectively. Conclusions: SBCE contributed to CD diagnosis in a quarter of patients with cPD after a negative standard workup. FC levels correlated with the degree of inflammation defined by the LS. However, the NPV of FC was low, suggesting that SBCE should be considered for patients with cPD even after a negative standard workup. [ABSTRACT FROM AUTHOR]

Background Heterogeneity in demographic and outcomes data with corresponding measurement instruments [MIs] creates barriers to data pooling and analysis. Several core outcome sets have been developed in inflammatory bowel disease [IBD] to homogenize outcomes data. A parallel Minimum Data Set [MDS] for baseline characteristics is lacking. We conducted a systematic review to develop the first MDS. Methods A systematic review was made of observational studies from three databases [2000–2021]. Titles and abstracts were screened, full-text articles were reviewed, and data were extracted by two reviewers. Baseline data were grouped into ten domains: demographics, clinical features, disease behaviour/complications, biomarkers, endoscopy, histology, radiology, healthcare utilization and patient-reported data. Frequency of baseline data and MIs within respective domains are reported. Results From 315 included studies [600 552 subjects], most originated from Europe [196; 62%] and North America [59; 19%], and were published between 2011 and 2021 [251; 80%]. The most frequent domains were demographics [311; 98.7%] and clinical [289; 91.7%]; 224 [71.1%] studies reported on the triad of sex [306; 97.1%], age [289; 91.7%], and disease phenotype [231; 73.3%]. Few included baseline data for radiology [19; 6%], healthcare utilization [19; 6%], and histology [17; 5.4%]. Ethnicity [19; 6%], race [17; 5.4%], and alcohol/drug consumption [6; 1.9%] were the least reported demographics. From 25 MIs for clinical disease activity, the Harvey–Bradshaw Index [ n  = 53] and Mayo score [ n  = 37] were most frequently used. Conclusions Substantial variability exists in baseline population data reporting. These findings will inform a future consensus for MDS in IBD to enhance data harmonization and credibility of real-world evidence. [ABSTRACT FROM AUTHOR]

Background and Aims Home self-injection of the human anti-tumour necrosis alpha [anti-TNFα] monoclonal adalimumab complicates prospective serial-sampling studies. Although a recent study examined adalimumab levels and immunogenicity in Crohn's disease [CD] patients, prospective real-world data from ulcerative colitis [UC] patients are lacking. Methods A three-monthly home-visit programme from induction was established prospectively for UC patients. Clinical scores were determined at each visit, and sera were obtained for assessment of drug and anti-adalimumab antibody levels. Calprotectin was measured using a smartphone-based app. This cohort was compared to a parallel prospective cohort of adalimumab-treated CD patients [POETIC1]. Results Fifty UC patients starting adalimumab [median follow-up 28 weeks] were compared to 98 adalimumab-treated CD patients [median follow-up 44 weeks]. Only 11/50 UC patients [22%] continued treatment to the end of the follow-up compared with 50/98 [51%] CD patients (odds ratio [OR] = 0.27, p  = 0.001). Loss of response was significantly more common in UC patients [OR = 3.2, p  = 0.001]. Seventeen patients [34%] in the UC cohort developed anti-adalimumab antibodies, 9/17 [52.9%] as early as week 2. There was no difference between patient cohorts in the overall development of anti-adalimumab antibodies [34% vs 30.6%, respectively, OR = 1.67, p  = 0.67], nor was there a difference in early immunogenicity [OR = 1.39, p  = 0.35]. There was no difference in low drug levels [<3 µg/mL] between the two cohorts [OR = 0.87, p  = 0.83]. Conclusions Loss of response to adalimumab therapy was significantly more common in the UC compared to the CD cohort and was driven by a higher rate of non-immunogenic, pharmacodynamic parameters. [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by increased stool frequency, rectal bleeding, and urgency. To streamline the quantitative assessment of histopathology using the Nancy Index in UC patients, we developed a novel artificial intelligence (AI) tool based on deep learning and tested it in a proof-of-concept trial. In this study, we report the performance of a modified version of the AI tool., Methods: Nine sites from 6 countries were included. Patients were aged ≥18 years and had UC. Slides were prepared with hematoxylin and eosin staining. A total of 791 images were divided into 2 groups: 630 for training the tool and 161 for testing vs expert histopathologist assessment. The refined AI histology tool utilized a 4-neural network structure to characterize images into a series of cell and tissue type combinations and locations, and then 1 classifier module assigned a Nancy Index score., Results: In comparison with the proof-of-concept tool, each feature demonstrated an improvement in accuracy. Confusion matrix analysis demonstrated an 80% correlation between predicted and true labels for Nancy scores of 0 or 4; a 96% correlation for a true score of 0 being predicted as 0 or 1; and a 100% correlation for a true score of 2 being predicted as 2 or 3. The Nancy metric (which evaluated Nancy Index prediction) was 74.9% compared with 72.3% for the proof-of-concept model., Conclusions: We have developed a modified AI histology tool in UC that correlates highly with histopathologists' assessments and suggests promising potential for its clinical application., (© 2024 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background and Aims: Fecal calprotectin (FC) is known to be a sensitive biomarker of colonic inflammation but to a lesser degree of small bowel (SB) inflammation. Moreover, data on FC's diagnostic levels in different SB segments are scarce. We aimed to examine FC's diagnostic levels along the SB-axis in CD., Methods: This was a post-hoc aggregated analysis of five prospective studies of adult CD patients, who underwent FC testing and SB video capsule endoscopy (VCE). Lewis score (LS) inflammation in different SB segments was tested for correlation with FC level after exclusion of colonic disease. The diagnostic levels of FC for SB inflammatory topographical-gradient were assessed using a receiver operating characteristic., Results: 214 patients were included (age:30 [24-43] year-old, males-57%). For a similar SB inflammatory-activity (LS≥135), FC levels incrementally increased from proximal to distal SB segments (63 [30-121] versus 190 [78-549], p=0.005) and from distal SB segment to the colon (190 [78-549] versus 542 [185-1000], p=0.010). The best FC cutoffs to identify isolated mild proximal/distal SB-inflammation (LS≥135) were 77μgg and 123μgg, respectively. A cutoff of 234μgg was best to detect more significant proximal inflammation (LS≥350) when only mild distal SB-inflammation was present. In sensitivity analyses, this proximal-to-distal FC gradient was maintained when LS≥350 and LS≥790 were used as the inflammatory reference-values. Unlike FC, the magnitude of CRP elevation was unrelated to the topography of inflammation along the SB-axis., Conclusions: FC may serve as a topographical biomarker of CD-activity, with its sensitivity to identify mucosal inflammation increases from proximal to distal SB segments., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: Drug sustainability (DS), a surrogate marker for drug efficacy, is important, especially when aiming for precision medicine. However, it lacks reliable prediction methods., Aims: To develop and externally validate a web-based artificial intelligence(AI)-derived tool for predicting DS of infliximab and vedolizumab in patients with moderate-to-severe Ulcerative Colitis (UC)., Methods: Data from three Israeli centers included infliximab or vedolizumab patients treated for >54 weeks. Sustainability meant no corticosteroids, hospitalizations or surgeries. Machine learning techniques predicted >54-week and overall DS using baseline clinical data., Results: The model was developed using data from 246 patients from Rabin Medical Center and externally validated on 67 patients from Rambam Health Care Campus and Sheba Medical Center. No significant difference in DS was observed across the datasets. Most patients were biologic-naïve and primarily treated with vedolizumab. The model performed well, with an area under the ROC curve of 0.86, and showed good accuracy (65.5 %-76.9 %) across the test sets., Conclusions: The study introduces a novel, AI-based tool for predicting >54-week DS of infliximab and vedolizumab in moderate-to-severe UC, using baseline parameters. This can aid clinical decision-making in the framework of precision medicine, promising to optimize disease management while maintaining physician autonomy., Competing Interests: Conflicts of interest HY- Has received research grants from Pfizer; consulting fees from Abbvie, Janssen, Pfizer, Takeda, and BMS; Speaker fees from Abbvie, Janssen, Pfizer, Takeda, and Bristol Myers Squibb; Data Safety Monitoring Board or Advisory Board fees from Abbvie, Pfizer Takeda and Bristol Myers Squibb. JEO- Has received grant support from Pfizer, consulting fees from Takeda, and speaker fees from Abbvie, Janssen, Pfizer, Takeda, Novartis, and Bristol Myers Squibb. IAB- Has received speaker fees from Abbvie, Janssen, Pfizer, Takeda, and Neopharm. ID- consultation fee or honorarium from: Abbott, Abbvie, Athos, Arena, Altman Research, Cambridge Healthcare, Celltrion, Celgene/BMS, Eli-Lilly, Ferring, Falk Pharma, Food Industries Organization, Gilead, Galapagos, Iterative Scopes, Integra Holdings, Janssen, Neopharm, Pfizer, Rafa laboratories, Roche/Genentech, Sangamo, Sublimity, Sandoz, Takeda, Wildbio. Grants: Altman Research, BMS, Pfizer UK- Research support- Jannsen, Takeda, Medtronic, speaker/advisory fees- Abbvie BMS Celtrion Jannsen Pfizer Takeda Medtronic Roche No specific funding has been received for this study., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

This article is the second in a series of two publications on the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of prior ECCO guidelines., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)