Search

Background and Aims: Pragmatic studies designed to test interventions in everyday clinical settings can successfully complement the evidence from registration and explanatory clinical trials. The European consensus project PRACTICE-IBD was developed to identify essential criteria and address key methodological issues needed to design valid, comparative, pragmatic studies in inflammatory bowel diseases [BDs]., Methods: Statements were issued by a panel of 11 European experts in IBD management and trial methodology, on four main topics: [I] study design; [II] eligibility, recruitment and organisation, flexibility; [III] outcomes; [IV] analysis. The consensus process followed a modified Delphi approach, involving two rounds of assessment and rating of the level of agreement [1 to 9; cut-off ≥7 for approval] with the statements by 18 additional European experts in IBD., Results: At the first voting round, 25 out of the 26 statements reached a mean score ≥7. Following the discussion that preceded the second round of voting, it was decided to eliminate two statements and to split one into two. At the second voting round, 25 final statements were approved: seven for study design; six for eligibility, recruitment and organisation, flexibility; eight for outcomes; and four for analysis., Conclusions: Pragmatic, randomised, clinical trials can address important questions in IBD clinical practice, and may provide complementary, high-level evidence, as long as they follow a methodologically rigorous approach. These 25 statements intend to offer practical guidance in the design of high-quality, pragmatic, clinical trials that can aid decision making in choosing a management strategy for IBDs., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Janus kinase (JAK) inhibitors and sphingosine 1 phosphate (S1P) receptor modulators are small molecule drugs (SMDs) approved for IBD treatment. Their use in clinical practice might be limited due to cardiovascular concerns. We aimed to provide guidance on risk assessment, monitoring, and management strategies, aiming to minimize potential cardiovascular risks of SMDs and to facilitate an adequate shared decision-making. A systematic literature search was conducted, and proposed statements were prepared. A virtual consensus meeting was held, in which eleven IBD physicians and two cardiovascular specialists from ten countries attended. Proposed statements were voted upon in an anonymous manner. Agreement was defined as at least 75 % of participants voting as 'agree' with each statement. Consensus was reached for eighteen statements. Available evidence does not show a higher risk of cardiovascular events with JAK inhibitors in the overall IBD population, although it might be increased in patients with an unfavorable cardiovascular profile. S1P receptor modulators may be associated with a risk of bradycardia, atrioventricular blocks, and hypertension. Cardiovascular risk stratification should be done before initiation of SMDs. Although the risk of cardiovascular events in patients with IBD on SMDs appears to be low overall, caution should still be taken in certain scenarios., Competing Interests: Conflict of Interest PAO declares no conflict of interest. AD reports fees for participation in clinical trials, review activities such as data monitoring boards, statistical analysis, and end point committees from Abivax, AbbVie, Arena Pharmaceuticals, Bristol Myers Squibb/Celgene, Dr Falk Foundation, Galapagos, Gilead, Janssen, and Pfizer; consultancy fees from AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Boehringer Ingelheim, Bristol Myers Squibb/Celgene, Celltrion, Dr Falk Foundation, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Janssen, Lilly, MSD, Pfizer, Pharmacosmos, Roche/Genentech, Sandoz/Hexal, Takeda, Tillotts, and Vifor Pharma; payment from lectures including service on speakers bureaus from AbbVie, Biogen, CED Service GmbH, Celltrion, Falk Foundation, Ferring, Galapagos, Gilead, High5MD, Janssen, Materia Prima, MedToday, MSD, Pfizer, Streamed-Up, Takeda, Tillotts, and Vifor Pharma; payment for manuscript preparation from Falk Foundation, Takeda, Thieme, and UniMed Verlag. MCD has received consulting fees from AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Pfizer Inc, Prometheus Laboratories, Takeda, and UCB. GP declares no conflict of interest. PGK: speaking and consultancy honorarium from Abbvie, Janssen, Pfizer and Takeda; Scientific grants from Pfizer and Takeda. ID has served as a speaker, consultant, or advisory board member for Takeda, Janssen, AbbVie, Pfizer, Eli-Lilly, Ferring, Roche/Genentech, Cambridge Healthcare, Celgene/BMS, Falk Pharma, Ierative Scopes, Rafa Laboratories, Neopharm, Arena, Gilead, Galapagos, Celltrion, Sublimity, Sandoz, Abbott, and Athos Therapeutics. TK has served as a speaker, a consultant or an advisory board member for AbbVie, Alfresa Pharma, Bristol Myers Squibb, Celltrion, Covidien, EA Pharma, Eisai, Eli Lilly, Ferring Pharmaceuticals, Gilead Sciences, Janssen, JIMRO, Kyorin Pharmaceutical, Kissei, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Sekisui Medical, Takeda Pharmaceutical, Zeria Pharmaceutical, and received research funding from AbbVie, Alfresa Pharma, EA Pharma, Gilead, Kyorin Pharmaceutical, Mochida Pharmaceutical, Nippon Kayaku, Otsuka Holdings, Pfizer, Sekisui Medical, Takeda Pharmaceutical, Zeria Pharmaceutical. SG reports research grants from GSK, Abbvie; Drug Monitoring Committee from Janssen, Steering Committees from BMS, Receptos, Janssen, Abbvie, Gilead, Galapagos; Lecture fees from Takeda, Pfizer, Janssen, Abbvie, BMS, Galapagos, Gilead, Celltrion and consulting fees from Abbvie, Janssen, Takeda, Pfizer, Galapagos, Celltrion, Ferring. FM has served as a speaker and received honoraria from Abbvie, Arena, Biogen, Bristol-Myers Squibb, Falk, Ferring, Hospira, Janssen, Laboratórios Vitoria, Pfizer, Lilly, Merck Sharp & Dohme, Sandoz, Takeda, UCB, and Vifor. JRFN declares no conflict of interest. BS has consulted for AbbVie, Arena, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Endpoint Health, Falk Pharma, Galapagos, Janssen, Landos, Lilly, Pfizer, Prometheus, and Takeda; has received speaker fees from AbbVie, CED Service GmbH, Falk Pharma, Ferring, Janssen, Novartis, Pfizer, and Takeda, and has received funding from Pfizer. SD has served as a speaker, consultant, and advisory board member for Schering-Plough, AbbVie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Johnson & Johnson, Millenium Takeda, MSD, NikkisoEurope GmbH, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, UCB Pharma, and Vifor. LPB reports personal fees from Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Index Pharmaceuticals, Sandoz, Celgene, Biogen, Samsung Bioepis, Inotrem, Al-lergan, MSD, Roche, Arena, Gilead, Amgen, BMS, Vifor, Norgine, Mylan, Lilly, Fresenius Kabi, OSE Immunotherapeutics, Enthera, Theravance, Pandion Therapeutics, Gossamer Bio, Viatris, Thermo Fisher; grants from AbbVie, MSD, Takeda, Fresenius Kabi; and has stock options in CTMA., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Integrating artificial intelligence into inflammatory bowel disease (IBD) has the potential to revolutionise clinical practice and research. Artificial intelligence harnesses advanced algorithms to deliver accurate assessments of IBD endoscopy and histology, offering precise evaluations of disease activity, standardised scoring, and outcome prediction. Furthermore, artificial intelligence offers the potential for a holistic endo-histo-omics approach by interlacing and harmonising endoscopy, histology, and omics data towards precision medicine. The emerging applications of artificial intelligence could pave the way for personalised medicine in IBD, offering patient stratification for the most beneficial therapy with minimal risk. Although artificial intelligence holds promise, challenges remain, including data quality, standardisation, reproducibility, scarcity of randomised controlled trials, clinical implementation, ethical concerns, legal liability, and regulatory issues. The development of standardised guidelines and interdisciplinary collaboration, including policy makers and regulatory agencies, is crucial for addressing these challenges and advancing artificial intelligence in IBD clinical practice and trials., Competing Interests: Declaration of interests MI: Olympus, Pentax (research grant and consultant fees). YMo: Olympus (consultation, device loan, and lecture fees) and Cybernet (license fee). All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Several advanced imaging techniques are now available for endoscopists managing inflammatory bowel disease (IBD) patients. These tools, including dye-based and virtual chromoendoscopy, probe-based confocal laser endomicroscopy and endocytoscopy, are increasingly innovative applications in clinical practice. They allow for a more in-depth and refined evaluation of the mucosal and vascular bowel surface, getting closer to histology. They have demonstrated a remarkable ability in assessing intestinal inflammation, histologic remission, and predicting relapse and favorable long-term outcomes. In addition, the future application of molecular endoscopy to predict biological drug responses has yielded preliminary but encouraging results. Furthermore, these techniques are crucial in detecting and characterizing IBD-related dysplasia, assisting endoscopic mucosal resection and submucosal dissection towards a surgery-sparing approach. Artificial intelligence (AI) holds great potential in this promising landscape, as it can provide an objective and reproducible assessment of inflammation and dysplasia. Moreover, it can improve the prediction of outcomes and aid in subsequent therapeutic decision-making. This review aims to summarize the promising role of state-of-the-art advanced endoscopic techniques and related AI-enabled models for managing IBD, paving the way for precision medicine., (© 2023 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Many patients with inflammatory bowel disease (IBD) have persistent symptoms and disease activity despite the best available medical or surgical treatments. These patients are commonly referred to as having difficult-to-treat IBD and need additional therapeutic strategies. However, the absence of standard definitions has impeded clinical research efforts and comparisons of data. Under the guidance of the endpoints cluster of the International Organization for the Study of Inflammatory Bowel Disease, we held a consensus meeting to propose a common operative definition for difficult-to-treat IBD. 16 participants from 12 countries voted on 20 statements covering various elements of difficult-to-treat IBD, such as failure of medical and surgical treatments, disease phenotypes, and specific complaints from patients. "Agreement" was defined as at least 75% consensus. The group agreed that difficult-to-treat IBD is defined by the failure of biologics and advanced small molecules with at least two different mechanisms of action, or postoperative recurrence of Crohn's disease after two surgical resections in adults, or one in children. In addition, chronic antibiotic-refractory pouchitis, complex perianal disease, and comorbid psychosocial complications that impair disease management also qualified as difficult-to-treat IBD. Adoption of these criteria could serve to standardise reporting, guide enrolment in clinical trials, and help identify candidates for enhanced treatment strategies., Competing Interests: Declaration of interests FDA has served as a speaker for Janssen, Galapagos, Sandoz, and Omega Pharma. MTA has served as a trainer or lecturer for Prime CME, Janssen Pharmaceuticals, Focus Medical Communications, Cornerstones Health, and Imedex; and as a consultant or advisor to Abbvie, Janssen, Gilead, Prometheus Biosciences, Takeda, UCB Biopharma SRL, Eli Lilly, Pfizer, Celsius, and Bristol Myers Squibb. AD has received research support or acted as a principal investigator for Abbvie, Dr Falk Pharma, Celgene/BMS, Gilead/Galapagos, Janssen, Biogen, and Takeda; has acted as a consultant for AbbVie, Abivax, Amgen, Boehringer Ingelheim, Celgene/BMS, Celltrion, Dr Falk Pharma, Ferring, Fresenius Kabi, Janssen, Lilly, MSD, Otsuka, Pfizer, Roche, Takeda, Tillotts, Pharmacosmos, and Vifor; and has participated in speaker bureaus for AbbVie, Amgen, BMS, Falk Foundation, Ferring, Galapagos, Janssen, Med Update, MSD, Pfizer, Roche, Takeda, Lilly, Tillotts, and Vifor. ID has served as a speaker, consultant, or advisory board member for Takeda, Janssen, AbbVie, Pfizer, Eli-Lilly, Ferring, Roche/Genentech, Cambridge Healthcare, Celgene/BMS, Falk Pharma, Ierative Scopes, Rafa Laboratories, Neopharm, Arena, Gilead, Galapagos, Celltrion, Sublimity, Sandoz, Abbott, and Athos Therapeutics. FM has served as a speaker and received honoraria from Abbvie, Arena, Biogen, Bristol-Myers Squibb, Falk, Ferring, Hospira, Janssen, Laboratórios Vitoria, Pfizer, Lilly, Merck Sharp & Dohme, Sandoz, Takeda, UCB, and Vifor. AFG has been a consultant for Abbvie, Amgen, Bristol Myers Squibb, Janssen, Lilly, Merck, Pfizer; and has received speaker fees from Abbvie and Janssen. VJ has received consulting or advisory board fees from AbbVie, Alimentiv (formerly Robarts Clinical Trials), Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Reistone Biopharma, Roche, Sandoz, Second Genome, Takeda, Teva, Topivert, Vividion; and speaker's fees from AbbVie, Ferring, Galapagos, Janssen Pfizer Shire, Takeda, and Fresenius Kabi. MI has received speaker fees from Pfizer; has received funding from the National Institute for Health and Care Research, Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham; and received research grants from Pentax, Fujinon, and Olympus. GJM has served as advisory board member for AbbVie, Celgene, Celtrion, Ferring, Genesis, Hospira, Janssen, Millennium Pharmaceuticals, Merck Sharp & Dohme, Mylan, Pharmacosmos, Pfizer, Takeda, and Vianex; has served as a speaker for AbbVie, Angelini, Falk Pharma, Ferring, Galenica, Cenesis, Hospira, Janssen, Merck Sharp & Dohme, Omega Pharma, Takeda, and Vianex; has served as a consultant for Merck Sharp & Dohme and Takeda; and has received research support from AbbVie, Galenica, Genesis, Menarini Group, and Merck Sharp & Dohme. WR has served as a speaker for Abbott Laboratories, AbbVie, Aesca, Aptalis, Astellas, Centocor, Celltrion, Danone Austria, Elan, Falk Pharma GmbH, Ferring, Immundiagnostik, Mitsubishi Tanabe Pharma Corporation, MSD, Otsuka, PDL, Pharmacosmos, PLS Education, Schering-Plough, Shire, Takeda, Therakos, Vifor, and Yakult; has served as a consultant for Abbott Laboratories, AbbVie, Aesca, Algernon, Amgen, AM Pharma, AMT, AOP Orphan, Arena Pharmaceuticals, Astellas, Astra Zeneca, Avaxia, Roland Berger GmBH, Bioclinica, Biogen IDEC, Boehringer-Ingelheim, Bristol Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Covance, Danone Austria, DSM, Elan, Eli Lilly, Ernest & Young, Falk Pharma GmbH, Ferring, Galapagos, Gatehouse Bio, Genentech, Gilead, Grünenthal, ICON, Index Pharma, Inova, Intrinsic Imaging, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, LivaNova, Mallinckrodt, Medahead, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Nash Pharmaceuticals, Nestle, Nippon Kayaku, Novartis, Ocera, OMass, Otsuka, Parexel, PDL, Periconsulting, Pharmacosmos, Philip Morris Institute, Pfizer, Procter & Gamble, Prometheus, Protagonist, Provention, Quell Therapeutics, Robarts Clinical Trial, Sandoz, Schering-Plough, Second Genome, Seres Therapeutics, Setpointmedical, Sigmoid, Sublimity, Takeda, Therakos, Theravance, Tigenix, UCB, Vifor, Zealand, Zyngenia, and 4SC; has served as an advisory board member for Abbott Laboratories, AbbVie, Aesca, Amgen, AM Pharma, Astellas, Astra Zeneca, Avaxia, Biogen IDEC, Boehringer-Ingelheim, Bristol Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Danone Austria, DSM, Elan, Ferring, Galapagos, Genentech, Grünenthal, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Nestle, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Sandoz, Schering-Plough, Second Genome, Setpointmedical, Takeda, Therakos, Tigenix, UCB, Zealand, Zyngenia, and 4SC; and has received research funding from Abbott Laboratories, AbbVie, Aesca, Centocor, Falk Pharma GmbH, Immundiagnostik, Janssen, MSD, Sandoz, and Takeda. DT reports consultation fees, research grants, royalties, or honorariaum from Janssen, Pfizer, Hospital for Sick Children (Canada), Ferring, AbbVie, Takeda, Atlantic Health System, Shire, Celgene, Lilly, Roche, ThermoFisher, and Bristol Myers Squibb. DTR has received grant support from Takeda, and has served as a consultant for Abbvie, Altrubio, Aslan Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene Chronicles, Corp/Syneos, ClostraBio, Connect BioPharma, Eco R1, Genentech/Roche, Gilead Sciences, Iterative Health, Janssen Pharmaceuticals, Kaleido Biosciences, Lilly, Pfizer, Prometheus Biosciences, Reistone, Seres Therapeutics, Takeda, Target RWE, and Trellus Health. LP-B reports personal fees from Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Index Pharmaceuticals, Sandoz, Celgene, Biogen, Samsung Bioepis, Inotrem, Al-lergan, MSD, Roche, Arena, Gilead, Amgen, BMS, Vifor, Norgine, Mylan, Lilly, Fresenius Kabi, OSE Immunotherapeutics, Enthera, Theravance, Pandion Therapeutics, Gossamer Bio, Viatris, Thermo Fisher; grants from AbbVie, MSD, Takeda, Fresenius Kabi; and has stock options in CTMA. SG declares consulting fees from Pfizer, Janssen, AbbVie, Takeda, Bristol-Myers Squibb, Receptos, Celgene, Gilead, Eli Lilly, and Boehringer Ingelheim; and speaker fees from AbbVie, Janssen, Takeda, Ferring, Shield, and Falk Pharma. SD has served as a speaker, consultant, and advisory board member for Schering-Plough, AbbVie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Johnson & Johnson, Millenium Takeda, MSD, Nikkiso Europe GmbH, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, UCB Pharma, and Vifor. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: We aimed to predict response to biologics in inflammatory bowel disease (IBD) using computerized image analysis of probe confocal laser endomicroscopy (pCLE) in vivo and assess the binding of fluorescent-labeled biologics ex vivo. Additionally, we investigated genes predictive of anti-tumor necrosis factor (TNF) response., Methods: Twenty-nine patients (15 with Crohn's disease [CD], 14 with ulcerative colitis [UC]) underwent colonoscopy with pCLE before and 12 to 14 weeks after starting anti-TNF or anti-integrin α4β7 therapy. Biopsies were taken for fluorescein isothiocyanate-labeled infliximab and vedolizumab staining and gene expression analysis. Computer-aided quantitative image analysis of pCLE was performed. Differentially expressed genes predictive of response were determined and validated in a public cohort., Results: In vivo, vessel tortuosity, crypt morphology, and fluorescein leakage predicted response in UC (area under the receiver-operating characteristic curve [AUROC], 0.93; accuracy 85%, positive predictive value [PPV] 89%; negative predictive value [NPV] 75%) and CD (AUROC, 0.79; accuracy 80%; PPV 75%; NPV 83%) patients. Ex vivo, increased binding of labeled biologic at baseline predicted response in UC (UC) (AUROC, 83%; accuracy 77%; PPV 89%; NPV 50%) but not in Crohn's disease (AUROC 58%). A total of 325 differentially expressed genes distinguished responders from nonresponders, 86 of which fell within the most enriched pathways. A panel including ACTN1, CXCL6, LAMA4, EMILIN1, CRIP2, CXCL13, and MAPKAPK2 showed good prediction of anti-TNF response (AUROC >0.7)., Conclusions: Higher mucosal binding of the drug target is associated with response to therapy in UC. In vivo, mucosal and microvascular changes detected by pCLE are associated with response to biologics in inflammatory bowel disease. Anti-TNF-responsive UC patients have a less inflamed and fibrotic state pretreatment. Chemotactic pathways involving CXCL6 or CXCL13 may be novel targets for therapy in nonresponders., (© 2022 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background & Aims: Fecal urgency, which is defined by the sudden need to rush to the bathroom to empty one's bowel, is one of the common and distressing symptoms experienced by patients with inflammatory bowel disease., Methods: We performed a narrative review to investigate the definition, pathophysiology, and therapeutic management of fecal urgency., Results: Definitions of fecal urgency in inflammatory bowel disease, but also in irritable bowel syndrome, oncology, nononcologic surgery, obstetrics and gynecology, and in proctology, are empirical and heterogenous, lacking standardization. In the majority of these studies, nonvalidated questionnaires were used. When nonpharmacologic measures (dietary regimen, cognitive behavioral program) fail, medications such as loperamide, tricyclic antidepressants, or biofeedback therapy may become necessary. Medical management of fecal urgency may be challenging, in part because only limited data are available regarding the treatment of this symptom in randomized clinical trials of biologics in patients with inflammatory bowel disease., Conclusions: There is an urgent need for a systematic approach to assessment of fecal urgency in inflammatory bowel disease. It is time to consider fecal urgency as an outcome in clinical trials to remedy this disabling symptom., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Diet influences the pathogenesis and clinical course of inflammatory bowel disease (IBD). The Mediterranean diet (MD) is linked to reductions in inflammatory biomarkers and alterations in microbial taxa and metabolites associated with health. We aimed to identify features of the gut microbiome that mediate the relationship between the MD and fecal calprotectin (FCP) in ulcerative colitis (UC). Weighted gene co-expression network analysis (WGCNA) was used to identify modules of co-abundant microbial taxa and metabolites correlated with the MD and FCP. The features considered were gut microbial taxa, serum metabolites, dietary components, short-chain fatty acid and bile acid profiles in participants that experienced an increase ( n = 13) or decrease in FCP ( n = 16) over eight weeks. WGCNA revealed ten modules containing sixteen key features that acted as key mediators between the MD and FCP. Three taxa ( Faecalibacterium prausnitzii, Dorea longicatena, Roseburia inulinivorans ) and a cluster of four metabolites (benzyl alcohol, 3-hydroxyphenylacetate, 3-4-hydroxyphenylacetate and phenylacetate) demonstrated a strong mediating effect (ACME: -1.23, p = 0.004). This study identified a novel association between diet, inflammation and the gut microbiome, providing new insights into the underlying mechanisms of how a MD may influence IBD. See clinicaltrials.gov (NCT04474561).

Background and Aims: Patient-centric management of inflammatory bowel disease [IBD] is important, with consensus considering patient-reported outcomes alongside clinical and endoscopic assessment by healthcare providers. However, evidence regarding patients' treatment priorities is still limited. This study aimed to elicit benefit-risk trade-offs that patients with IBD are willing to make, to help inform discussions about patient-centric treatment targets., Methods: This was a cross-sectional online survey of adults with self-confirmed Crohn's disease [CD] or ulcerative colitis [UC] receiving IBD treatment. The impact of efficacy, administration and safety on treatment preferences was elicited using a discrete choice experiment. Relative attribute importance [RAI] and maximum acceptable risk of mild-to-moderate side effects [SEs] were estimated from a mixed logit model., Results: In total, 400 patients [CD: 54%; UC: 46%; female: 38.0%; age range: 18-78 years] were recruited. Efficacy, administration and safety affected treatment preferences to varying degrees, with abdominal pain being most important [RAI 33%] followed by risks of mild-to-moderate SEs [RAI 27%] and serious infections [RAI 16%]. To reduce abdominal pain from severe to moderate/mild, patients accepted an additional 18.8% or 30.6% risk of mild-to-moderate SEs, respectively. While average preferences between patients with CD and UC were similar, patients with CD placed greater importance on abdominal pain [p < 0.05], and patients with UC on bowel urgency [p < 0.05]. However, preferences varied notably., Conclusions: While avoiding abdominal pain, SEs and serious infections had on average the highest treatment priority, preferences varied between patients. Treatment strategies should consider the trade-offs individuals are willing to make., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: Crohn's disease has a substantial negative impact on health-related quality of life (HRQoL)., Aim: To examine the effects of risankizumab on HRQoL in Crohn's disease METHODS: We analysed data from patients with Crohn's disease from 12-week induction trials ADVANCE (N = 850) and MOTIVATE (N = 569) with risankizumab 600 mg or 1200 mg intravenous (IV) versus placebo IV and a 52-week maintenance trial FORTIFY (N = 462) with risankizumab 180 or 360 mg subcutaneous (SC) versus placebo SC. Outcomes included Inflammatory Bowel Disease Questionnaire (IBDQ), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), 36-item Short Form Health Survey (SF-36), EuroQol 5-Dimension-5-Level (EQ-5D-5L) and work productivity. The mean change and percentages of patients achieving clinically meaningful improvement in all outcomes were determined at weeks 12 and 52., Results: At week 12, more patients in the risankizumab 600 or 1200 mg groups achieved IBDQ response than with placebo (ADVANCE: 70.2%, 75.5% vs. 47.8%, p ≤ 0.001; MOTIVATE: 61.7%, 68.5% vs. 48.2%, p ≤ 0.01) and FACIT-F response (ADVANCE: 51.3%, 48.0% vs. 35.7%, p ≤ 0.01; MOTIVATE: 44.2%, 49.1% vs. 33.7%, p < 0.05). These improvements persisted at week 52 with risankizumab maintenance treatment. Similar trends were observed for SF-36 physical and mental component summary scores, EQ-5D-5L and activity impairment within work productivity measures., Conclusions: Risankizumab induction therapy (600 or 1200 mg IV) led to clinically meaningful improvements in disease-specific and general patient-reported outcomes, including fatigue, in patients with moderate to severe Crohn's disease. These improvements were sustained after 52 weeks of risankizumab (180 or 360 mg SC) maintenance therapy., (© 2022 AbbVie Inc. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Endoscopic remission is now considered the ultimate long-term goal for treating inflammatory bowel disease (IBD). Recent advances in endoscopic techniques have progressively added new tools to the armamentarium of endoscopists for a deeper assessment and characterisation of the intestinal mucosa. Virtual Electronic chromoendoscopy is widely available in the endoscopic units, leading to a more accurate evaluation of the vascular and mucosal architecture of the colon, reducing the gap with histology, which is considered a favourable long-term measure. In addition, advanced, sophisticated techniques such as endocytoscope and confocal laser endomicroscopy provide insights into individualised and personalised IBD therapy. Finally, high expectations are placed on the advent of Artificial Intelligence (AI) with promising applications that have the potential to revolutionise IBD diagnosis and management. Here, we discuss state-of-the-art of endoscopic techniques and their applicability to accurate assess endoscopic and histological remission, predict response to therapy and detect, characterise and guide treatment of colonic dysplastic lesions. We are seeing the dawn of a new era wherein the applications of these new endoscopic tools, hand in hand with AI, offer the most incredible opportunity to deliver precision medicine to patients with IBD., (© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: Despite advancement in the treatment of inflammatory bowel disease (IBD), induction and maintenance of remission remain challenging to achieve in many patients and a significant proportion of patients with IBD experience mental health conditions, including anxiety, depression, and fatigue, which impair their quality of life (QoL). We aim to describe the available evidence regarding the effects of physical activity (PA) on the onset of IBD, its disease course, and important patient-reported outcome measures (PROMs), such as QoL, fatigue, and mental health., Methods: A literature search was performed using electronic databases to identify original articles that assessed the effects of PA in patients with IBD using PROMs., Results: Prospective cohort and case-control studies demonstrate inverse relationships between PA and new-onset IBD in Crohn's disease but not in ulcerative colitis; however, they have small sample sizes and caution must be taken in considering associations versus causation. Small randomized controlled trials suggest promise for PA and beneficial outcomes, such as maintenance of clinical remission and improvement in QoL, fatigue, depression, and anxiety. However, these studies were small and underpowered, and limited by outcome measurements and durations of follow-up., Conclusions: Physicians may consider discussing PA interventions with their patients on an individual basis, especially if they report impaired QoL, fatigue, depression, or anxiety, until disease-specific guidelines are available. Including PA as part of a primary prevention strategy in high-risk patients could be considered., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Interleukin 23 [IL-23] plays a key role in the pathogenesis of both Crohn's disease [CD] and ulcerative colitis [UC], promoting a Th17 cell-related immune response. The combined blockade of IL-23 and IL-12 with ustekinumab has been demonstrated to be safe and effective in the treatment of inflammatory bowel disease [IBD]. Studies on preclinical models and observations of other immune-mediated diseases, such as psoriasis, suggest that the selective inhibition of IL-23 could be beneficial in IBD. Four monoclonal antibodies [risankizumab, mirikizumab, brazikumab and guselkumab] are currently in advance clinical trials for either CD or UC. In this review, we provide an overview of the main results from published studies of selective anti IL-23 agents., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Inflammatory bowel diseases (IBD) are chronic disorders of the gastrointestinal tract with an increasing prevalence worldwide. Targeted therapies for IBD are limited by several factors, including the therapeutic ceiling and the high incidence of non-responders or loss-of-response. In order to improve therapeutic efficacy, there is critical need to decipher disease pathogenesis, currently not well understood. Macrophages, innate immune cells that exhibit high plasticity, perpetuate inflammatory signalling in IBD through excessive release of inflammatory mediators. In recent years, pioneering research has revealed the importance of the interplay between macrophages and gut microbiota in maintaining intestinal homeostasis. Particular attention is focusing on microbiota-derived metabolites, believed to possess immunomodulatory properties capable of manipulating macrophage plasticity. Microbiota-derived short-chain fatty acids (SCFAs) and indole compounds, along with dietary sourced omega-3 (ω-3) polyunsaturated fatty acids (PUFA), exert anti-inflammatory effects, attributable to interactions with macrophages. Before we can effectively incorporate these metabolites into IBD therapies, a deeper understanding of microbiota-macrophage interactions at a molecular level is necessary. Therefore, the aim of this review is firstly to detail current knowledge regarding how diet and microbiota-derived metabolites modify macrophage plasticity. Later, we discuss the concept of therapeutic strategies directed at microbiota-macrophage interactions, which could be highly valuable for IBD therapies in the future.

Background: Telemedicine plays an important role in the management of inflammatory bowel disease (IBD), particularly during a pandemic such as COVID-19. However, the effectiveness and efficiency of telemedicine in managing IBD are unclear., Objective: This systematic review and meta-analysis aimed to compare the impact of telemedicine with that of standard care on the management of IBD., Methods: We systematically searched the PubMed, Cochrane Library, EMBASE, Web of Science, and Scopus databases on April 22, 2020. Randomized controlled trials comparing telemedicine with standard care in patients with IBD were included, while conference abstracts, letters, reviews, laboratory studies, and case reports were excluded. The IBD-specific quality of life (QoL), disease activity, and remission rate in patients with IBD were assessed as primary outcomes, and the number of in-person clinic visits per patient, patient satisfaction, psychological outcome, and medication adherence were assessed as secondary outcomes. Review Manage 5.3 and Stata 15.1 were used for data analysis., Results: A total of 17 randomized controlled trials (2571 participants) were included in this meta-analysis. The telemedicine group had higher IBD-specific QoL than the standard care group (standard mean difference 0.18, 95% CI 0.01 to 0.34; P.03). The number of clinic visits per patient in the telemedicine group was significantly lower than that in the standard care group (standard mean difference -0.71, 95% CI -1.07 to -0.36; P<.001). Subgroup analysis showed that adolescents in the telemedicine group had significantly higher IBD-specific QoL than those in the standard care group (standard mean difference 0.42, 95% CI 0.15 to 0.69; I2=0; P.002), but there was no significant difference between adults in the 2 groups. There were no significant differences in disease activity, remission rate, patient satisfaction, depression, self-efficacy, generic QoL, and medication adherence outcomes between the telemedicine and standard care groups., Conclusions: Telemedicine intervention showed a promising role in improving IBD-specific QoL among adolescents and decreased the number of clinic visits among patients with IBD. Further research is warranted to identify the group of patients with IBD who would most benefit from telemedicine., (©Lanlan Pang, Hengyu Liu, Zhidong Liu, Jinyu Tan, Long-yuan Zhou, Yun Qiu, Xiaoqing Lin, Jinshen He, Xuehua Li, Sinan Lin, Subrata Ghosh, Ren Mao, Minhu Chen. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 24.03.2022.)

Background: IBD, both Crohn's disease and ulcerative colitis, is associated with significant functional disability. Gastrointestinal symptoms alone are not the sole purpose of the interaction between patients and providers. In order to ascertain patients' disabilities, we utilized the recently developed IBD Disk to help determine their functional concerns and initiate relevant conversation. We aimed to ascertain patient acceptability and their major disabilities., Patients and Methods: In this multicenter study, IBD patients at their outpatient visit were given the paper version of the IBD Disk. Patients were asked to score their level of disability for each item of the IBD Disk. The completed scores were then shared with their healthcare provider to act as a focus of discussion during the consultation. Patients and clinicians were also asked to provide informal qualitative feedback as to the benefits of the IBD Disk and areas for improvement., Results: A total of 377 (female 60%) patients completed the questionnaires over the study period. Patient acceptability scored on a 0-10 Likert scale was excellent. All patients scored all domains of disability. Sleep, energy, and joint pain were the highest scoring domains of the IBD Disk, scoring higher than digestive symptoms. Clinicians and patients agreed that the IBD Disk allowed for ease of communication about disability symptoms and relevance to their day-to-day functioning., Conclusion: The IBD Disk is a novel easy-to-use tool to assess the functional disability of patients. We next plan to utilize it in the form of an electronic app internationally and in relation to treatment commencement and escalation., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Patients with inflammatory bowel disease (IBD) are at increased risk of thrombotic events. Therapies for IBD have the potential to modulate this risk. The aims of this Evidence-Based Guideline were to summarize available evidence and to provide practical recommendations regarding epidemiological aspects, prevention and drug-related risks of venous and arterial thrombotic events in patients with IBD. A virtual meeting took place in May 2020 involving 14 international IBD experts and 3 thrombosis experts from 12 countries. Proposed statements were voted upon in an anonymous manner. Agreement was defined as at least 75% of participants voting as 'fully agree' or 'mostly agree' with each statement. For each statement, the level of evidence was graded according to the Scottish Intercollegiate Guidelines Network (SIGN) grading system. Consensus was reached for 19 statements. Patients with IBD harbour an increased risk of venous and arterial thrombotic events. Thromboprophylaxis is indicated during hospitalization of any cause in patients with IBD. Disease activity is a modifiable risk factor in patients with IBD, and physicians should aim to achieve deep remission to reduce the risk. Exposure to steroids should be limited. Antitumour necrosis factor agents might be associated with a reduced risk of thrombotic events., (© 2021. The Author(s).)

Inflammatory bowel diseases, principally Crohn's disease and ulcerative colitis, are multifactorial chronic conditions. Alterations in gut microbial patterns partly affect disease onset and severity. Moreover, the evolution of dietary patterns, and their effect on gut microbial behaviour, have been shown to play a crucial role in disease processes. This Viewpoint reviews the role of dietary patterns, their influence on the structure and function of the gut microbiome, and their effects on inflammation and immunity in individuals with inflammatory bowel disease. We also discuss innovative dietary intervention strategies, summarise findings that have been used to develop recommendations for clinical practice, and provide suggestions for the design of future studies for development of precision nutrition in patients with inflammatory bowel disease., Competing Interests: Conflict of interests SCN declares being a board member and speaker for Pfizer, Ferring, Janssen, and AbbVie; and speaker at Tillotts, Menarini, and Takeda. GGK has received honoraria for speaking or consultancy from AbbVie, Janssen, Pfizer, and Takeda; he has received research support from Ferring, Janssen, AbbVie, GlaxoSmith Kline, Merck, and Shire; he has been a consultant for Gilead; he shares ownership of a patent (WO2019046959A1. PCT/CA2018/051098). SG reports grants and personal fees from AbbVie; personal fees from Janssen, Takeda, Pfizer, Gilead, Galapagos, Boehringer Ingelheim, BMS, and Celltrion; and grants from GSK, outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Competing Interests: SD has served as a speaker, consultant, and advisory board member for Schering-Plough, AbbVie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Johnson and Johnson, Millennium Takeda, Merck Sharp & Dohme, Nikkiso Europe, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, UCB Pharma, and Vifor. LPB reports personal fees from Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Pharmacosmos, Celltrion, Takeda, Boehringer Ingelheim, Pfizer, Index Pharmaceuticals, Sandoz, Celgene, Biogen, Samsung Bioepis, Alma, Sterna, Nestle, Inotrem, Enterome, Allergan, MSD, Roche, Arena, Gilead, Hikma, Amgen, Bristol Myers Squibb, Vifor, Norgine, Mylan, Lilly, Fresenius Kabi, Oppilan Pharma, Sublimity Therapeutics, Applied Molecular Transport, OSE Immunotherapeutics, Enthera, and Theravance; has received grants from AbbVie, Merck Sharp & Dohme, and Takeda; and has stock options from Clinical Trials Mobile Application. SG is a steering committee member for Pfizer, Janssen, AbbVie, Bristol Myers Squibb, Celgene, and Boehringer Ingelheim and has received speaker honoraria from AbbVie, Janssen, Takeda, Shield, Ferring, and Falk Pharma. TLP declares no competing interests.

Background: Mucosal healing (MH) is a key treatment target in the management of inflammatory bowel disease (IBD) and is defined in endoscopic terms by the newly published PICaSSO score. Raman Spectroscopy (RS) is based on the scattering of inelastic light giving spectra that are highly specific for individual molecules. We aimed to establish spectral changes before and after treatment and whether Raman Spectroscopy is able to accurately differentiate between inflammation and MH., Methods: Biopsies were taken for ex vivo RS analysis alongside biopsies for histological analysis from IBD patients undergoing optical diagnosis endoscopic assessment. We compared pre- vs. post-biological treatment in IBD patients and healthy controls and active vs. MH in UC and CD. For spectral analysis, we used supervised self-organising maps for separation and classification., Results: A total of 23 patients (14 IBD, 9 HC) were recruited for comparison of pre- vs. post-biologic treatment and 74 IBD patients were included for the assessment of MH in IBD, giving 9700 Raman Spectra. Spectral differences were seen between pre- and post-treatment which were observed comparing MH vs. active inflammation. Reductions in intensity at 1003cm-1 and 1252cm-1 when a reduction in inflammation was seen post-treatment and when MH was present. MH was associated with an increase in intensity at 1304cm-1. The trained neural network differentiated MH from active inflammation with a sensitivity, specificity, PPV, NPV and accuracy in UC of 96.29% (sd 0.94), 95.03% (sd 1.52), 94.89% (sd 1.59), 96.33 (sd 0.97) and 95.65 (sd 0.99) and 96.19% (sd 1.46), 88% (sd 4.20), 86.60% (sd 5.39), 96.55% (sd 1.32) and 91.6% (sd 2.75) in CD respectively., Conclusion: We demonstrated RS can demonstrate biochemical changes following treatment of IBD and accurately differentiates MH from active inflammation in IBD and might be a future tool to personalise therapeutic management in IBD., Competing Interests: The authors have declared that no competing interests exist.

Background: Fecal calprotectin (FC) is a non-invasive marker of gut inflammation which is frequently used to guide therapeutic decisions in patients with inflammatory bowel diseases (IBD). Each step of FC measurement can influence the results, leading to misinterpretations and potentially impacting the management of IBD patients. To date, there is high heterogeneity between FC measurements and no current method is universally accepted as a standard., Aims: Our aim was to provide clear position statementsabout the pre-analytical and the analytical phases of FC measurement to homogenize FC levels and to minimize variability and risk of misinterpretation through aninternational consensus., Materials & Methods: Fourteen physicians with expertise in the field of IBD and FC from 11 countries attended a virtual international consensus meeting on July 17th, 2020. A systematic literature was conducted and the literature evidence was shared and discussedamong the participants. Statements were formulated, discussed, and voted. Statements were considered approved if all participants agreed., Results: Nine statements were formulated and approved. Based on the available evidence, quantitative tests should be preferred for measuring FC. Furthermore, FC measurement, if possible, should always be performed with the same method and factors influencing FC levels should be taken into account when interpreting the results., Discussion: FC has an increasingly important role in the management of patients with IBD. However, large multicenter studies should be conducted to define the reproducibility and to confirm the diagnostic accuracy of the available FC tests., Conclusion: FC concentrations guide clinicians' treatment decisions. Our statements have a relevant impact in daily practice and could be applied in clinical trials to standardize FC measurement., (© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

Background and Aims: Epidemics pose a great challenge to health care of patients. However, the impact of unprecedented situation of COVID-19 outbreak on health care of inflammatory bowel disease (IBD) patients in real-world setting has seldom been investigated., Methods: We performed an observational study in a tertiary referral IBD center in China. The mode of health care and medication use was compared before and after COVID-19 outbreak. Electronic questionnaire surveys were performed among gastroenterologists and IBD patients to investigate the impact of COVID-19 outbreak on their attitudes towards telemedicine., Results: COVID-19 outbreak resulted in substantial decrease of patients participating in standard face-to-face visit during 1 month post-outbreak (n = 51) than pre-outbreak (n = 249), whereas the participation in telemedicine was significantly higher than comparable period in 2019 (414 vs 93). During the 1 month after COVID-19 outbreak, 39 (39/56, 69.6%) patients had their infliximab infusion postponed with the mean delay of 3 weeks. The immunomodulator use was similar between pre-outbreak and post-outbreak. Six elective surgeries were postponed for a median of 43 days. In post-outbreak period, 193 (193/297, 64.98%) of the surveyed physicians have used telemedicine with an increase of 18.9% compared with 46.13% (137/292) in the pre-outbreak period (P < 0.001); 331 (331/505, 65.54%) of the surveyed IBD patients supported that the use of telemedicine should be increased in future health care., Conclusion: COVID-19 outbreak resulted in a great change in health-care access among IBD patients including decrease in standard face-to-face visit and delay of biologics use. There was an increased use and need of telemedicine after COVID-19 outbreak., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

There have been immediate and profound impacts of SARS-CoV-2 and COVID-19 on health care services worldwide, with major consequences for non COVID-19 related health care. Alongside efforts to reconfigure services and enable continued delivery of safe clinical care for patients with IBD, consideration must also be given to management of IBD research activity. In many centres there has been an effective shutdown of IBD clinical trial activity as research sites have switched focus to either COVID-19 related research or clinical care only. As a result, the early termination of trial programmes, and loss of potentially effective therapeutic options for IBD, has become a real and worrying prospect. Moreover, in many countries research activity has become embedded into clinical care-with clinical trials often providing access to new therapies or strategies-which would otherwise not have been available in standard clinical pathways. This pandemic has significant implications for the design, conduct, analysis, and reporting of clinical trials in IBD. In this Viewpoint, we share our experiences from a clinical and academic perspective in the UK, highlighting the early challenges encountered, and consider implications for patients and staff at research sites, sponsors, research ethics committees, funders, and regulators. We also offer potential solutions both for now and for when we enter a recovery phase from the pandemic., (© The Author(s) 2020. 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.)

Background: IL6-IL6R-STAT3-SOCS3 signaling pathway is known to play important roles in regulating intestinal epithelial homeostasis, in pathogenesis of inflammatory bowel disease (IBD), and in tumorigenesis of colorectal neoplasia. We studied the expressions of these factors in IBD-associated dysplasia and compared to sporadic colorectal adenomas in non-IBD individuals., Materials and Methods: The expression of IL6, IL6R, STAT3, and SOCS3 within dysplastic as well as background non-dysplastic epithelial cells was evaluated by immunohistochemistry in 26 sporadic colorectal adenomas in non-IBD patients, 32 adenoma-like and 30 non-adenoma-like dysplastic lesions in IBD (41 ulcerative colitis, 21 Crohn's disease) patients. The level of expression of each factor was arbitrarily scored as 0, 1, 2, and 3., Results: In both IBD and non-IBD lesions, neoplastic epithelium showed a higher expression of all factors, except the IL6R, as compared to non-neoplastic epithelium. For non-neoplastic epithelium between IBD and non-IBD settings, the colitic epithelium showed a similar IL6, lower IL6R, higher STAT3, and higher SOCS3 expression. As compared to non-IBD adenomas, IBD-associated dysplasia showed a significantly lower IL6, lower IL6R, higher STAT3, and lower SOCS3 expression. Most notably, a parallel-elevation pattern of STAT3/SOCS3 expressions was seen in non-IBD adenomas but an inverse-expression pattern of STAT3/SOCS3 seen in IBD dysplastic lesions. No significant differences existed between adenoma-like and non-adenoma-like lesions., Conclusions: IL6/IL6R-STAT3-SOCS3 signaling pathway does not seem to be preferentially associated with IBD-associated dysplasia. However, the STAT3-SOCS3 interaction appears dysregulated in IBD, characterized by a loss of STAT3/SOCS3 balance,i.e., loss of the normal negative regulation of SOCS3., (Copyright © 2020. Published by Elsevier GmbH.)

The incidence and prevalence of ulcerative colitis are increasing globally. Although the exact cause and pathogenesis of this disease is unclear, research has led to a better understanding of the condition and to identification of new targets for therapy, which in turn has encouraged the development of new therapies. As well as biologic therapies, which have changed the way inflammatory bowel disease is managed, small molecules have been developed for the treatment of ulcerative colitis. These small molecule treatments are orally administered and are likely to bring a substantial shift in the way this chronic disease is treated. Oral therapies offer many advantages over infusion therapies, such as ease of use, increased acceptability by patients, and reduction of cost. This Review focuses not only on oral therapies that have been approved for use in ulcerative colitis, but also on those that are in development, providing a comprehensive overview for clinicians of available oral therapies and drugs that are likely to become available. We have also reviewed drugs that have shown promise in preclinical studies and could be effective future therapies., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aims: Inflammatory bowel disease (IBD)-associated precancerous lesions may be adenomatous or non-adenomatous with various histomorphologies. We aim to validate the newly proposed classification, to explore the neoplastic nature of the non-adenomatous lesions and to elucidate the molecular mechanisms underlying the different histomorphologies., Methods: 44 background precursor lesions identified in 53 cases of surgically resected IBD-associated colorectal and ileal carcinomas were reviewed for the histomorphological features (classified into adenomatous, mucinous, sessile serrated adenoma (SSA)-like, traditional serrated adenoma-like, differentiated, eosinophilic and serrated not otherwise specified (NOS)) and analysed for a key panel of colonic cancer-related molecular markers., Results: Approximately 60% of the lesions were adenomatous, of which some had mixed serrated, mucinous or eosinophilic changes. The remaining non-adenomatous lesions, including all other types except SSA-like type, mostly showed mixed features and focal adenomatous dysplasia. KRAS mutation and p53 mutant-type expression were found in about half cases across all types, while PIK3CA mutation only in some of adenomatous and eosinophilic lesions and MLH1/PMS2 loss in a subset of adenomatous, mucinous and eosinophilic but not in differentiated and serrated lesions. SAT-B2 or PTEN loss and IMP3 overexpression were seen in a small subset of lesions. No BRAF , NRAS or EGFR gene mutation was detected in any type. Certain molecular-morphological correlations were demonstrated; however, no single or combined molecular alteration(s) was specific to any particular morphological type., Conclusions: IBD-associated precancerous lesions are heterogeneous both histologically and molecularly. True colitis-associated adenomatous lesions are unlikely conventional adenomas. Non-adenomatous lesions without frank cytologic dysplasia should also be regarded as neoplastic., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

The COVID-19 pandemic is putting unprecedented pressures on healthcare systems globally. Early insights have been made possible by rapid sharing of data from China and Italy. In the UK, we have rapidly mobilised inflammatory bowel disease (IBD) centres in order that preparations can be made to protect our patients and the clinical services they rely on. This is a novel coronavirus; much is unknown as to how it will affect people with IBD. We also lack information about the impact of different immunosuppressive medications. To address this uncertainty, the British Society of Gastroenterology (BSG) COVID-19 IBD Working Group has used the best available data and expert opinion to generate a risk grid that groups patients into highest, moderate and lowest risk categories. This grid allows patients to be instructed to follow the UK government's advice for shielding, stringent and standard advice regarding social distancing, respectively. Further considerations are given to service provision, medical and surgical therapy, endoscopy, imaging and clinical trials., Competing Interests: Competing interests: For details of conflicts of interest see online supplementary table 1., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The coronavirus disease 2019 (COVID-19) pandemic is changing the management of many chronic diseases, including that of patients with inflammatory bowel diseases (IBD). In particular, the performance of routine endoscopy is temporarily suspended, and only emergency endoscopy is allowed in many countries where severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread. We highlight different scenarios in which endoscopy should still be performed urgently in patients with IBD, as well as recommendations regarding the use of personal protective equipment. We suggest a pathway for performing safe endoscopy and discuss the potential risks of postponing endoscopy in IBD. Finally, we propose a post-pandemic plan for access to endoscopy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Distinct histomorphologic features of colitis-associated dysplasia (CAD) or neoplastic precursors in inflammatory bowel disease (IBD) have never been clearly identified. In this study, we tried to further explore the differentiating morphologic features of CAD by retrospectively reviewing the lesions that were clearly associated with carcinomas (carcinoma-related lesions) and by comparing between endoscopically nonpolypoid (non-adenoma-like) lesions and polypoid (adenoma-like) lesions and sporadic conventional adenomas found in the noncolitic mucosa and in patients without IBD. Our study results have revealed that (1) precursor lesions related to IBD-associated colorectal carcinomas were almost always nonpolypoid in macroscopic/endoscopic appearance; (2) nearly half of the carcinoma-related lesions and nonpolypoid lesions were similarly nonadenomatous (nonconventional) lesions, largely serrated type, with no or only mild/focal adenomatous dysplasia, and commonly had mixed adenomatous and nonadenomatous features; (3) carcinoma-related and nonpolypoid adenomatous dysplastic lesions frequently showed some peculiar histocytologic features that we observed and described for the first time, including mixed features of inflammatory pseudopolyps or granulation tissue, pleomorphic and disarrayed nuclei, micropapillary or hobnailing surface epithelial cells, and microvesicular or bubbling cytoplasm of dysplastic cells; and (4) polypoid lesions in the colitic mucosa were identical to sporadic adenomas in the noninflamed mucosa and in patients without IBD, and they lacked the aforementioned features. The seemingly distinctive morphologic characteristics that we proposed here, although still not absolutely specific or unique, can be used as the features of inclusion for identifying CAD on endoscopic biopsies when the endoscopy images are not readily available to pathologists and thus to alert clinicians for a closer follow-up., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The traditional management of inflammatory bowel disease (IBD) based on symptom control is not considered valid anymore by most specialists in this field, and a new paradigm called "treat to target" has been introduced. This is based on the assessment of disease activity using objective measures. The identification of noninvasive biomarkers is crucial to diagnosis and monitor IBD because frequent endoscopic examinations are costly and uncomfortable for the patient. In this review, we focus on blood markers that may be able to assess mucosal healing (MH) in IBD and recent advances in this area. Introduction of commercial panel to predict MH opens the way for further developments so that colonoscopy or fecal markers may be avoided in some patients. This may also permit frequent monitoring for therapeutic response and achieve MH. It is a challenging area of research to identify a panel of biomarkers that may reflect inflammation and healing to serve as a surrogate of MH., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Transition care in inflammatory bowel disease is increasingly recognized as challenging given the inherent differences between paediatric and adult health care models, disease characteristics and treatment strategies. Transition is a dynamic process involving adolescents and young adults that are moving from a paediatric to an adult health care setting, and it should be flexible, continually updated and tailored to each patient. The implementation of a transition clinic is essential given the increasing incidence of the paediatric population with inflammatory bowel disease and the lifelong impact of this disease. The key question is when and how to structure transition according to the adolescent's clinical, psycho-social, educational needs and expectations to ensure continuity of care. In the attempt to improve the management of transition in inflammatory bowel disease and address the wide gap between adult and child care, we provide an update of the transition clinic and we propose a "treat to target" approach in transition to facilitate an effective and successful transition programme. In the changing landscape of the treatment of inflammatory bowel disease, further studies are necessary to determine the role of the transition clinic in determining the choice and strategy of therapy and its monitoring and the adoption of newer strategies such as biomarkers guided treating to target., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: The incidence of inflammatory bowel diseases (IBD) is increasing in Latin America. We performed a systematic review to identify clinical and epidemiologic features of IBD in Latin America (including Mexico, Central America, and South America) and the Caribbean., Methods: We searched MEDLINE, EMBASE, and SciELO databases for clinical or epidemiologic studies of Crohn's disease (CD) or ulcerative colitis (UC) from Latin American and Caribbean countries and territories that reported incidence, prevalence, ratio of UC:CD, IBD phenotype, and treatment, through September 12, 2018. Data were extracted from 61 articles for analysis., Results: The incidence and prevalence of IBD have been steadily increasing in Latin America and the Caribbean. The incidence of CD in Brazil increased from 0.08 per 100,000 person-years in 1988 to 0.68 per 100,000 person-years in 1991-1995 to 5.5 per 100,000 person-years in 2015. The highest reported prevalence of IBD was in Argentina, in 2007, at 15 and 82 per 100,000 person-years for CD and UC, respectively. The ratio of UC:CD exceeded 1 in all regions throughout Latin America and the Caribbean with the exception of Brazil. Treatment with tumor necrosis factor antagonists increased steadily for patients with CD (43.4% of all patients in Brazil were treated in 2014) but less so for patients with UC (4.5% of all patients were treated in 2014). Surgery for IBD decreased with time. In Chile, surgeries were performed on 57.0% of patients with CD and 18.0% of patients with UC during the period of 1990-2002; these values decreased to 38.0% and 5.0%, respectively, during the period of 2012-2015. In Peru, 6.9% of patients with UC received colectomies in the period of 2001-2003 and 6.2% in 2004-2014., Conclusions: In a systematic review, we found the incidence of IBD to be increasing throughout Latin America and the Caribbean. Population-based epidemiology studies are needed to evaluate the increase in IBD in these regions, which differ from other global regions in climate, culture, demographics, diet, healthcare delivery and infrastructure, and socioeconomic status., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

It is the current view that the inflammatory bowel disease (IBD)-associated precancerous lesions may be adenomatous (with classic cytologic dysplasia) and non-adenomatous (without frank cytologic dysplasia), and the latter ones are in various histomorphologies including serrated, mucinous, eosinophilic (goblet cell deficient), and differentiated (dysplasia with terminal epithelial differentiation) types. By retrospectively reviewing the surgically resected IBD-associated colorectal and ileal carcinomas (×53), analyzing the background epithelial changes/lesions in the mucosa surrounding and adjacent to invasive carcinomas, and testing the key molecular profile (KRAS, BRAF, PIK3CA, NRAS, p53, mismatch repair proteins, and SAT-B2) known to be involved in colorectal carcinogenesis, we identified 6 representative, rare and unique cases, in which non-adenomatous lesions were clearly in vicinity and in transition to invasive carcinomas. Furthermore, we identified certain colonic carcinoma-related molecular alterations, and thus further confirmed the neoplastic nature of various non-adenomatous lesions. It was also revealed that non-adenomatous lesions are heterogeneous in both morphology and molecular alterations, and that it is common to have more than one type of lesions be associated with a carcinoma. Moreover, mixed focal adenomatous dysplasia was common, which may be the necessary step in the malignant transformation of the non-adenomatous lesions., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Several recommendations have addressed the topic of improving the quality of surveillance colonoscopy in inflammatory bowel disease. However, there is variation between these recommendations, in part due to the absence of well-defined quality indicators, suggesting that these quality indicators should be studied and developed. We did a systematic review of evidence related to surveillance colonoscopy in inflammatory bowel disease to look at the different variables in this practice and offer a critique of the quality control measures before, during, and after the procedure. We identified several key quality measures that could be adopted in clinical practice, including control of inflammation, optimal bowel preparation, ideal time allocation, training, sedation, detection and characterisation of lesions, therapeutic management of the lesions, and colonoscopic reports. However, further primary research and consensus reports are needed to continue developing roadmaps at a global level., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background and Aims: The effect of smoking on the risk of developing inflammatory bowel diseases (IBD) may be heterogeneous across ethnicity and geography. Although trends in smoking for the general population are well described, it is unknown whether these can be extrapolated to the IBD cohort. Smoking prevalence trends specific to the global IBD cohort over time have not been previously reported. This is a systematic review of smoking prevalence specific to the IBD cohort across geography., Methods: A systematic literature search was conducted on Medline and Embase from January 1st 1946 to April 5th 2018 to identify population-based studies assessing the prevalence of smoking at diagnosis in inception cohorts of Crohn's disease(CD) or ulcerative colitis(UC). Studies that did not report smoking data from time of diagnosis or the year of IBD diagnosis were excluded. Prevalence of smoking in IBD was stratified by geography and across time., Results: We identified 56 studies that were eligible for inclusion. Smoking prevalence data at diagnosis of CD and UC was collected from twenty and twenty-five countries respectively. Never-smokers in the newly diagnosed CD population in the West has increased over the last two decades, especially in the United Kingdom and Sweden; +26.6% and +11.2% respectively. Never-smokers at CD diagnosis in newly industrialised nations have decreased over the 1990s and 2000s; China (-19.36%). Never-smokers at UC diagnosis also decreased in China; -15.4%. The former-smoker population at UC diagnosis in China is expanding; 11%(1990-2006) to 34%(2011-2013)., Conclusion: There has been a reduction in the prevalence of smoking in the IBD cohort in the West. This is not consistent globally. Although, smoking prevalence has decreased in the general population of newly industrialised nations, this remains an important risk factor with longer term outcomes awaiting translation in both UC and CD., Competing Interests: The authors have declared that no competing interests exist.

The incidence and prevalence of Inflammatory Bowel Disease (IBD) has rapidly increased worldwide and now is a global disease with some of the highest rates observed in North America [...].

Inflammatory bowel diseases (IBDs) develop in genetically predisposed individuals in response to environmental factors. IBDs are concomitant conditions of industrialized societies, and diet is a potential culprit. Consumption of ultra-processed food has increased over the last decade in industrialized countries, and epidemiological studies have found associations between ultra-processed food consumption and chronic diseases. Further studies are now required to identify the potential culprit in ultra-processed food, such as a poor nutritional composition or the presence of food additives. In our review, we will focus on food additives, i.e., substances from packaging in contact with food, and compounds formed during production, processing, and storage. A literature search using PubMed from inception to January 2019 was performed to identify relevant studies on diet and/or food additive and their role in IBDs. Manuscripts published in English from basic science, epidemiological studies, or clinical trials were selected and reviewed. We found numerous experimental studies highlighting the key role of food additives in IBD exacerbation but epidemiological studies on food additives on IBD risk are still limited. As diet is a modifiable environmental risk factor, this may offer a scientific rationale for providing dietary advice for IBD patients.

Vitamin D has been linked to human health benefits that extend far beyond its established actions on calcium homeostasis and bone metabolism. One of the most well studied facets of extra-skeletal vitamin D is its activity as an immuno-modulator, in particular its potent anti-inflammatory effects. As a consequence, vitamin D deficiency has been associated with inflammatory diseases including inflammatory bowel disease (IBD). Low serum levels of the major circulating form of vitamin D, 25-hydroxyvitamin D (25-OH-D) are significantly more prevalent in patients with IBD, particularly in the winter and spring months when UV-induced synthesis of vitamin D is lower. Dietary malabsorption of vitamin D may also contribute to low serum 25(OH)D in IBD. The benefits of supplementation with vitamin D for IBD patients are still unclear, and improved vitamin D status may help to prevent the onset of IBD as well as ameliorating disease severity. Beneficial effects of vitamin D in IBD are supported by pre-clinical studies, notably with mouse models, where the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25-(OH)2D) has been shown to regulate gastrointestinal microbiota function, and promote anti-inflammatory, tolerogenic immune responses. The current narrative review aims to summarise the different strands of data linking vitamin D and IBD, whilst also outlining the possible beneficial effects of vitamin D supplementation in managing IBD in humans.

Background: Perianal abscess [PA] is associated with inflammatory bowel disease [IBD]. The incidence of IBD after a diagnosis of PA and potential predictors of a future diagnosis of IBD are unknown., Methods: The Health Improvement Network [THIN] is a primary care database representative of the UK population. Incident cases of PA were identified between 1995 and 2017. Subjects with PA were matched to controls within the same general practice. The primary outcome was a subsequent diagnosis of Crohn's Disease [CD] or ulcerative colitis [UC]. A Cox regression model was used to assess potential predictors of a new diagnosis of CD or UC following PA., Results: The risk of CD was higher in the PA cohort compared with controls; adjusted hazard ratio [HR] 7.51 (95% confidence interval [CI] 4.86-11.62), p < 0.0001. The risk of UC was also higher in the PA cohort compared with controls; adjusted HR 2.03 [1.38-2.99], p < 0.0001. Anaemia in men (HR 2.82 [1.34-5.92], p = 0.002), and use of antidiarrhoeal medications (HR 2.70 [1.71-4.25], p < 0.0001) were associated with an increased risk of CD following PA. Anaemia in men (HR 2.58 [1.09-6.07], p = 0.03), diarrhoea (HR 2.18 [1.23-3.85], p = 0.007), and use of anti-diarrhoeal medication (HR 2.27 [1.19-4.30], p = 0.012) were associated with an increased risk of UC following PA., Conclusion: Subjects with PA are at an increased risk of subsequent diagnosis of CD and UC. Clinicians should strongly consider investigation for IBD in young patients presenting with diarrhoea and anaemia [in males] following PA. Future research should discern appropriate screening strategies for this high-risk cohort., (Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Hospitalisation rates for inflammatory bowel disease (IBD) vary across the world. We aimed to investigate temporal patterns of hospitalisation for IBD in member countries of the Organisation for Economic Co-operation and Development (OECD)., Methods: From the OECD database, we assessed IBD-related hospitalisation rates (expressed as annual rates per 100 000 inhabitants) for 34 countries from 1990 to 2016. We calculated mean hospitalisation rates for the period 2010-15 and used joinpoint regression models to calculate average annual percentage changes with 95% CIs., Findings: Mean hospitalisation rates for IBD from 2010 to 2015 were highest in North America (eg, 33·9 per 100 000 in the USA), Europe (eg, 72·9 per 100 000 in Austria), and Oceania (eg, 31·5 per 100 000 in Australia). Hospitalisation rates for IBD were stabilising or decreasing over time in many countries in these regions but increasing in others. Countries in Asia and Latin America and the Caribbean had the lowest IBD-related hospitalisation rates but the greatest increases in rates over time. For example, Turkey had an annual hospitalisation rate of 10·8 per 100 000 inhabitants and an average annual percentage change of 10·4% (95% CI 5·2-15·9). Similarly, Chile had an annual hospitalisation rate of 9·0 per 100 000 inhabitants and an average annual percentage change of 5·9% (4·9-7·0)., Interpretation: Hospitalisation rates for IBD are high in western countries but are typically stabilising or decreasing, whereas rates in many newly industrialised countries are rapidly increasing, which reflects the known increase in IBD prevalence in these countries. Potential explanations for these trends include changes in the epidemiology of IBD, health-care delivery, and infrastructure in these countries, as well as overall country-specific patterns in hospitalisations and differences between countries in data collection methods., Funding: None., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Biological therapy is currently widely used to treat IBD. Infliximab, adalimumab and golimumab are currently licensed anti-TNF therapies. Biosimilar anti-TNF monoclonal antibodies are increasingly used. Anti-TNF therapies are widely used and their adverse effects are well characterised, and may cause significant morbidity and mortality in a small proportion of exposed patients. Gastroenterologists need to understand the mechanisms for these effects, recognise these swiftly and manage such events appropriately., Aim: To cover the range of potential adverse reactions as a result of biologic therapy and specifically management of these events., Methods: A Medline and Pubmed search was undertaken. Search terms included were "anti-TNF," "infliximab" or "adalimumab" or "golimumab" combined with the keywords "ulcerative colitis" or "Crohn's disease" or "inflammatory bowel disease" and then narrowed to articles containing the keywords "complications," "side effects" or "adverse events" or "safety profile." International guidelines were also reviewed where relevant., Results: Adverse events discussed in this review include infusion reactions, blood disorders and infections (including bacterial, viral, fungal and opportunistic infections) as well as autoimmune, dermatological disorders, cardiac and neurological conditions. Malignancies including solid organ, haematological and those linked to viral disease are discussed., Conclusions: Anti-TNF therapy has wide-ranging effects on the immune system resulting in a spectrum of potential adverse events in a small proportion of patients. Research advances are improving the understanding, recognition and management of these adverse events., (© 2019 John Wiley & Sons Ltd.)

Endoscopic assessment of inflammation and mucosal healing is crucial for appropriate management in IBD. Current definition of endoscopic mucosal healing has been derived using previous generation of standard white light endoscopes. New endoscopy technologies widely available provide much more detailed images of mucosal and vascular patterns. Novel endoscopic techniques with high definition image, optical and digital enhancement have enhanced the quality and fine details of vascular and mucosal pattern so that endoscopic images have started to reflect histological changes for lesions and inflammation/healing. These technologies can now define subtle inflammatory changes and increase detection and characterisation of colonic lesions in patients with IBD. The best endoscopic technique to detect dysplasia in IBD is still debated. Dye chromoendoscopy with targeted biopsies is considered by Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in inflammatory Bowel Disease Patients: International Consensus Recommendations (SCENIC consensus the standard of care and recommended for adoption by gastroenterologists in practice. In future, it is possible that well-trained colonoscopists using high definition equipment with image enhancements may be able to obtain equivalent yield without pan-colonic dye spraying and characterise lesions. Finally, SCENIC introduced endoscopic resectability of some dysplastic colonic lesions-new techniques may now better characterise endoscopic resectability and limit the number of colectomies. In this review, we will provide a state-of-the-art opinion on the direction of technological advances in the assessment of IBD and how new concepts will refine clinical practice., Competing Interests: Competing interests: MI: received research support from Pentax, Olympus and Fujifilm; Speaker fees from Pentax. SG: Received speaker fees from Abbvie, Janssen, Takeda., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Characterization of colonic lesions in inflammatory bowel disease (IBD) remains challenging. We developed an endoscopic classification of visual characteristics to identify colitis-associated neoplasia using multimodal advanced endoscopic imaging (Frankfurt Advanced Chromoendoscopic IBD LEsions [FACILE] classification)., Methods: The study was conducted in three phases: 1) development - an expert panel defined endoscopic signs and predictors of dysplasia in IBD and, using multivariable logistic regression created the FACILE classification; 2) validation - using 60 IBD lesions from an image library, two assessments of diagnostic accuracy for neoplasia were performed and interobserver agreement between experts using FACILE was determined; 3) reproducibility - the reproducibility of the FACILE classification was tested in gastroenterologists, trainees, and junior doctors after completion of a training module., Results: The experts initially selected criteria such as morphology, color, surface, vessel architecture, signs of inflammation, and lesion border. Multivariable logistic regression confirmed that nonpolypoid lesion, irregular vessel architecture, irregular surface pattern, and signs of inflammation within the lesion were predictors of dysplasia. Area under the curve of this logistic model using a bootstrapped estimate was 0.76 (0.73 - 0.78). The training module resulted in improved accuracy and kappa agreement in all nonexperts, though in trainees and junior doctors the kappa agreement was still moderate and poor, respectively., Conclusion: We developed, validated, and demonstrated reproducibility of a new endoscopic classification (FACILE) for the diagnosis of dysplasia in IBD using all imaging modalities. Flat shape, irregular surface and vascular patterns, and signs of inflammation predicted dysplasia. The diagnostic performance of all nonexpert participants improved after a training module., Competing Interests: Dr Iacucci has received an unrestricted research grant from Pentax USA. Dr. Sanduleanu has received an unrestricted research grant from Pentax Europe., (© Georg Thieme Verlag KG Stuttgart · New York.)