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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).)

Background: Multiple investigations are available to aid the diagnosis and monitoring of disease activity in inflammatory bowel disease (IBD). Fecal calprotectin (FC) is an established surrogate for intestinal inflammatory activity. Therapeutic drug monitoring (TDM) including thiopurine metabolites, anti-tumor necrosis factor (TNF) levels and antidrug antibody measurements are a step toward personalized medicine in IBD, but face access barriers. We aimed to assess test availability and barriers for these investigations in European practice., Methods: Five-hundred questionnaires were distributed to workshop participants at the 11th Congress of the European Crohn's and Colitis Organisation (ECCO). Access to FC, TDM for thiopurines and anti-tumor necrosis factor agents, as well as factors associated with usage and barriers to access were recorded., Results: Responses were obtained from 195 attendees from 38 countries across a range of practices, healthcare settings and levels of experience. FC was available to 92.3% while access to anti-TNF (78.9%, P = 0.02 vs.  thiopurine TDM, P = 0.0002 vs.  FC) and thiopurine TDM (67.7%, P = 0.0001) were less widespread. Cost was a frequently cited barrier to test access or usage, with access having a significant West-East and North-South divide across all three investigations. The strongest independent predictor of access to all tests was healthcare spending per capita (P = 0.005 for FC; P < 0.0001 for both TDM)., Conclusion: FC, anti-TNF and thiopurine TDM are increasingly incorporated as part of routine practice in IBD care across Europe and have the potential to impact positively on patient care. However, access barriers remain of which we found test cost the most significant with the investment required to reduce these barriers., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Inflammatory bowel disease is a chronic disease with variable degrees of extent, severity, and activity. A proportion of patients will have disease that is refractory to licensed therapies, resulting in significant impairment in quality of life. The treatment of these patients involves a systematic approach by the entire multidisciplinary team, with particular consideration given to medical options including unlicensed therapies, surgical interventions, and dietetic and psychological support. The purpose of this review is to guide clinicians through this process and provide an accurate summary of the available evidence for different strategies., (© The Author(s) 2021. 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.)

Objective: Delayed second dose SARS-CoV-2 vaccination trades maximal effectiveness for a lower level of immunity across more of the population. We investigated whether patients with inflammatory bowel disease treated with infliximab have attenuated serological responses to a single dose of a SARS-CoV-2 vaccine., Design: Antibody responses and seroconversion rates in infliximab-treated patients (n=865) were compared with a cohort treated with vedolizumab (n=428), a gut-selective anti-integrin α4β7 monoclonal antibody. Our primary outcome was anti-SARS-CoV-2 spike (S) antibody concentrations, measured using the Elecsys anti-SARS-CoV-2 spike (S) antibody assay 3-10 weeks after vaccination, in patients without evidence of prior infection. Secondary outcomes were seroconversion rates (defined by a cut-off of 15 U/mL), and antibody responses following past infection or a second dose of the BNT162b2 vaccine., Results: Geometric mean (SD) anti-SARS-CoV-2 antibody concentrations were lower in patients treated with infliximab than vedolizumab, following BNT162b2 (6.0 U/mL (5.9) vs 28.8 U/mL (5.4) p<0.0001) and ChAdOx1 nCoV-19 (4.7 U/mL (4.9)) vs 13.8 U/mL (5.9) p<0.0001) vaccines. In our multivariable models, antibody concentrations were lower in infliximab-treated compared with vedolizumab-treated patients who received the BNT162b2 (fold change (FC) 0.29 (95% CI 0.21 to 0.40), p<0.0001) and ChAdOx1 nCoV-19 (FC 0.39 (95% CI 0.30 to 0.51), p<0.0001) vaccines. In both models, age ≥60 years, immunomodulator use, Crohn's disease and smoking were associated with lower, while non-white ethnicity was associated with higher, anti-SARS-CoV-2 antibody concentrations. Seroconversion rates after a single dose of either vaccine were higher in patients with prior SARS-CoV-2 infection and after two doses of BNT162b2 vaccine., Conclusion: Infliximab is associated with attenuated immunogenicity to a single dose of the BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines. Vaccination after SARS-CoV-2 infection, or a second dose of vaccine, led to seroconversion in most patients. Delayed second dosing should be avoided in patients treated with infliximab., Trial Registration Number: ISRCTN45176516., Competing Interests: Competing interests: NAK reports grants from F. Hoffmann-La Roche AG, grants from Biogen Inc, grants from Celltrion Healthcare, grants from Galapagos NV, non-financial support from Immundiagnostik, during the conduct of the study; grants and non-financial support from AbbVie, grants and personal fees from Celltrion, personal fees and non-financial support from Janssen, personal fees from Takeda, personal fees and non-financial support from Dr Falk, outside the submitted work. SL reports non-financial support from Pfizer, non-financial support from Ferring, outside the submitted work. JRG reports grants from F. Hoffmann-La Roche AG, grants from Biogen, grants from Celltrion Healthcare, grants from Galapagos NV, non-financial support from Immundiagnostik, during the conduct of the study. DC reports non-financial support from Ferring, personal fees and non-financial support from Pfizer, outside the submitted work. JRFC reports grants and personal fees from Samsung, Pfizer & Biogen; personal fees and non-financial support from Janssen & Abbvie; grants, personal fees and non-financial support from Takeda; personal fees from MSD, Sandoz, Celltrion & NAPP, outside the submitted work. AF reports personal fees from Takeda UK Ltd, personal fees from Dr Falk Pharma, personal fees from Tillotts, personal fees from Abbvie Ltd, personal fees from Sheild, personal fees from Ferring, from Pharmacosmos, personal fees from Allergan, personal fees from Janssen, outside the submitted work. PMI reports grants and personal fees from Takeda, grants from MSD, grants and personal fees from Pfizer, personal fees from Galapagos, personal fees from Gilead, personal fees from Abbvie, personal fees from Janssen, personal fees from Boehringer Ingelheim, personal fees from Topivert, personal fees from VH2, personal fees from Celgene, personal fees from Arena, personal fees from Samsung Bioepis, personal fees from Sandoz, personal fees from Procise, personal fees from Prometheus, outside the submitted work. NK reports personal fees from Janssen, outside the submitted work. KBK reports personal fees from Janssen, personal fees from Takeda, personal fees from PredictImmune, personal fees from Amgen, outside the submitted work. CAL reports grants from Genentech, grants and personal fees from Janssen, grants and personal fees from Takeda, grants from AbbVie, personal fees from Ferring, grants from Eli Lilly, grants from Pfizer, grants from Roche, grants from UCB Biopharma, grants from Sanofi Aventis, grants from Biogen IDEC, grants from Orion OYJ, personal fees from Dr Falk Pharma, grants from AstraZeneca, outside the submitted work. JM reports grants and personal fees from Takeda Pharmaceuticals, grants and personal fees from Biogen, personal fees and non-financial support from AbbVie, personal fees from Grifols, personal fees from Sandoz, personal fees from Celltrion, personal fees and non-financial support from Janssen, personal fees from Vifor Pharmaceuticals, personal fees from Predictimmune, personal fees from Bristol Myers Squibb, non-financial support from Ferring Pharmaceuticals, outside the submitted work. RCGP reports acting as consultant, advisory board member, speaker or recipient of educational grant from Dr Falk, Ferring, Janssen, Pharmacosmos and Takeda. TR reports grants and personal fees from Abbvie, personal fees from BMS, personal fees from Celgene, personal fees from Ferring, personal fees from Gilead, personal fees from GSK, personal fees from LabGenius, personal fees from Janssen, personal fees from Mylan, personal fees from MSD, personal fees from Novartis, personal fees from Pfizer, personal fees from Sandoz, personal fees from Takeda, personal fees from Galapagos, personal fees from Arena, outside the submitted work. PJS reports speaker fees and advisory board sponsorship from Janssen, Celltrion and Takeda outside the submitted work. AMV reports personal fees and non-financial support from Takeda, personal fees and non-financial support from Celltrion, personal fees and non-financial support from Merck Sharp & Dohme, outside the submitted work. SJ is an employee of Roche Diagnostics and holds Roche shares. SS reports grants from Takeda, Abbvie, AMGEN, Tillots Pharma, personal fees from Jaansen, Takeda, Galapagos, Celltrion, Falk Pharma, Tillots pharma, Cellgene, Pfizer, Pharmacocosmos, outside the submitted work. CWL reports personal fees from Abbvie, personal fees from Janssen, personal fees from Pfizer, personal fees from Takeda, grants from Gilead, personal fees from Gilead, personal fees from Galapagos, personal fees from Iterative Scopes, personal fees from Trellus Health, personal fees from Celltion, personal fees from Ferring, personal fees from BMS, during the conduct of the study. NP reports personal fees from Takeda, personal fees from Janssen, personal fees from Pfizer, personal fees from Bristol-Myers Squibb, personal fees from Abbvie, personal fees from Roche, personal fees from Lilly, personal fees from Allergan, personal fees from Celgene, outside the submitted work; and NP has served as a speaker/advisory board member for Abbvie, Allergan, Bristol Myers Squibb, Celgene, Falk, Ferring, Janssen, Pfizer, Tillotts, Takeda and Vifor Pharma. TA reports grants and non-financial support from F. Hoffmann-La Roche AG, grants from Biogen Inc, grants from Celltrion Healthcare, grants from Galapagos NV, non-financial support from Immundiagnostik, during the conduct of the study; personal fees from Biogen, grants and personal fees from Celltrion Healthcare, personal fees and non-financial support from Immundiagnostik, personal fees from Takeda, personal fees from ARENA, personal fees from Gilead, personal fees from Adcock Ingram Healthcare, personal fees from Pfizer, personal fees from Genentech, non-financial support from Tillotts, outside the submitted work., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Multiple studies have described the effectiveness of ustekinumab (UST) and vedolizumab (VDZ) in patients with Crohn's disease (CD) failing anti- Tumor necrosis factors (TNFs); however, the effectiveness of VDZ or UST as a third-class biologic has not yet been described., Aims and Methods: In this retrospective multicenter cohort study, we aimed to investigate the effectiveness of VDZ and UST as a third-class biologic in patients with CD., Results: Two-hundred and four patients were included; 156/204 (76%) patients received VDZ as a second- and UST as a third-class therapy (group A); the remaining 48/204 (24%) patients received UST as a second- and VDZ as a third-class therapy (group B). At week 16-22, 87/156 (55.5%) patients and 27/48 (56.2%) in groups A and B, respectively, responded to treatment ( p = 0.9); 41/156 (26.2%) and 15/48 (31.2%) were in clinical remission ( p = 0.5). At week 52; 89/103 (86%) patients and 25/29 (86.2%) of the patients with available data had responded to third-class treatment in groups A and B, respectively ( p = 0.9); 31/103 (30%) and 47/29 (24.1%) were in clinical remission ( p = 0.5)., Conclusion: Third-class biological therapy was effective in more than half of the patients with CD. No differences in effectiveness were detected between the use of VDZ and UST as a third-class agent.

Objective: Antitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination and increase the risk of serious respiratory infections. We sought to determine whether infliximab-treated patients with IBD have attenuated serological responses to SARS-CoV-2 infections., Design: Antibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4β7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections. 6935 patients were recruited from 92 UK hospitals between 22 September and 23 December 2020., Results: Rates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab-treated than vedolizumab-treated patients (3.4% (161/4685) vs 6.0% (134/2250), p<0.0001). Multivariable logistic regression analyses confirmed that infliximab (vs vedolizumab; OR 0.66 (95% CI 0.51 to 0.87), p=0.0027) and immunomodulator use (OR 0.70 (95% CI 0.53 to 0.92), p=0.012) were independently associated with lower seropositivity. In patients with confirmed SARS-CoV-2 infection, seroconversion was observed in fewer infliximab-treated than vedolizumab-treated patients (48% (39/81) vs 83% (30/36), p=0.00044) and the magnitude of anti-SARS-CoV-2 reactivity was lower (median 0.8 cut-off index (0.2-5.6) vs 37.0 (15.2-76.1), p<0.0001)., Conclusions: Infliximab is associated with attenuated serological responses to SARS-CoV-2 that were further blunted by immunomodulators used as concomitant therapy. Impaired serological responses to SARS-CoV-2 infection might have important implications for global public health policy and individual anti-TNF-treated patients. Serological testing and virus surveillance should be considered to detect suboptimal vaccine responses, persistent infection and viral evolution to inform public health policy., Trial Registration Number: ISRCTN45176516., Competing Interests: Competing interests: NAK reports grants from F. Hoffmann-La Roche AG, grants from Biogen Inc, grants from Celltrion Healthcare, grants from Galapagos NV, non-financial support from Immundiagnostik, during the conduct of the study; grants and non-financial support from AbbVie, grants and personal fees from Celltrion, personal fees and non-financial support from Janssen, personal fees from Takeda, personal fees and non-financial support from Dr Falk, outside the submitted work. JRG reports grants from F. Hoffmann-La Roche AG, grants from Biogen Inc, grants from Celltrion Healthcare, grants from Galapagos NV, non-financial support from Immundiagnostik, during the conduct of the study. DC reports non-financial support from Ferring, personal fees and non-financial support from Pfizer, outside the submitted work. SL reports non-financial support from Pfizer, non-financial support from Ferring, outside the submitted work. RC reports personal fees from Takeda, outside the submitted work. NMC reports trial funding, advisory board and speaker fees paid to his institution from AbbVie, Eli Lilly, Takeda, Shire, Pfizer and Janssen. ALH reports personal fees from Abbvie, personal fees from Allergan, personal fees from BMS, personal fees from Celltrion, personal fees from Falk, personal fees from GSK, personal fees from Takeda, personal fees from Pfizer, personal fees from Janssen, personal fees from Galapogos, personal fees from Astra Zeneca, outside the submitted work. PMI reports grants and personal fees from Takeda, grants from MSD, grants and personal fees from Pfizer, personal fees from Galapagos, personal fees from Gilead, personal fees from Abbvie, personal fees from Janssen, personal fees from Boehringer Ingelheim, personal fees from Topivert, personal fees from VH2, personal fees from Celgene, personal fees from Arena, personal fees from Samsung Bioepis, personal fees from Sandoz, personal fees from Procise, personal fees from Prometheus, outside the submitted work. KBK reports personal fees from Janssen, personal fees from Takeda, personal fees from PredictImmune, personal fees from Amgen, outside the submitted work. CAL reports grants from Genentech, grants and personal fees from Janssen, grants and personal fees from Takeda, grants from AbbVie, personal fees from Ferring, grants from Eli Lilly, grants from Pfizer, grants from Roche, grants from UCB Biopharma, grants from Sanofi Aventis, grants from Biogen IDEC, grants from Orion OYJ, personal fees from Dr Falk Pharma, grants from AstraZeneca, outside the submitted work. JKL reports personal fees from MSD, personal fees from Janssen, grants and personal fees from Takeda, grants and personal fees from Galapagos, personal fees from Tillotts, outside the submitted work. JM reports grants and personal fees from Takeda Pharmaceuticals, grants and personal fees from Biogen, personal fees and non-financial support from AbbVie, personal fees from Grifols, personal fees from Sandoz, personal fees from Celltrion, personal fees and non-financial support from Janssen, personal fees from Vifor Pharmaceuticals, personal fees from Predictimmune, personal fees from Bristol Myers Squibb, non-financial support from Ferring Pharmaceuticals, outside the submitted work. DPBM reports grants from the Leona M. and Harry B. Helmsley Charitable Trust, during the conduct of the study; personal fees from Takeda Pharmaceuticals, personal fees from Pfizer, personal fees from Bridge Biotherapeutics, personal fees from Palatin Technologies, personal fees from Boehringer-Ingelheim, personal fees and other from Prometheus Biosciences, personal fees from Gilead, outside the submitted work. KVP reports personal fees and non-financial support from Takeda, personal fees and non-financial support from Janssen, personal fees and non-financial support from Abbvie, personal fees from DrFalk, non-financial support from Ferring, outside the submitted work. RCGP reports acting as consultant, advisory board member, speaker or recipient of educational grant from Dr Falk, Ferring, Janssen, Pharmacosmos and Takeda. TR reports grants and personal fees from Abbvie, personal fees from BMS, personal fees from Celgene, personal fees from Ferring, personal fees from Gilead, personal fees from GSK, personal fees from LabGenius, personal fees from Janssen, personal fees from Mylan, personal fees from MSD, personal fees from Novartis, personal fees from Pfizer, personal fees from Sandoz, personal fees from Takeda, personal fees from Galapagos, personal fees from Arena, outside the submitted work. RKR reports grants from NHS Research Scotland Senior Research Fellowship, personal fees from Nestlé, personal fees from AbbVie, personal fees from Dr Falk, personal fees from Takeda, personal fees from Napp, personal fees from Mead Johnson, personal fees from Nutricia, personal fees from 4D Pharma, outside the submitted work. CPS reports grants and personal fees from AbbVie, grants and personal fees from Janssen, grants and personal fees from Takeda, personal fees from Dr Falk, personal fees from Pfizer, personal fees from Galapagos, personal fees from Arena, personal fees from Fresenius Kabi, outside the submitted work. PJS reports speaker fees and advisory board sponsorship from Janssen, Celltrion and Takeda outside the submitted work. CWL reports personal fees from Abbvie, personal fees from Janssen, personal fees from Pfizer, personal fees from Takeda, grants from Gilead, personal fees from Gilead, personal fees from Galapagos, personal fees from Iterative Scopes, personal fees from Trellus Health, personal fees from Celltion, personal fees from Ferring, personal fees from BMS, during the conduct of the study. SS reports grants from Takeda, Abbvie, AMGEN, Tillots Pharma, personal fees from Jaansen, Takeda, Galapagos, Celltrion, Falk Pharma, Tillots pharma, Cellgene, Pfizer, Phamrmacocosmos, outside the submitted work. NP reports personal fees from Takeda, personal fees from Janssen, personal fees from Pfizer, personal fees from Bristol-Myers Squibb, personal fees from Abbvie, personal fees from Roche, personal fees from Lilly, personal fees from Allergan, personal fees from Celgene, outside the submitted work; and NP has served as a speaker/advisory board member for Abbvie, Allergan, Bristol Myers Squibb, Celgene, Falk, Ferring, Janssen, Pfizer, Tillotts, Takeda and Vifor Pharma. TA reports grants and non-financial support from F. Hoffmann-La Roche AG, grants from Biogen Inc, grants from Celltrion Healthcare, grants from Galapagos NV, non-financial support from Immundiagnostik, during the conduct of the study; personal fees from Biogen Inc, grants and personal fees from Celltrion Healthcare, personal fees and non-financial support from Immundiagnostik, personal fees from Takeda, personal fees from ARENA, personal fees from Gilead, personal fees from Adcock Ingram Healthcare, personal fees from Pfizer, personal fees from Genentech, non-financial support from Tillotts, outside the submitted work., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

The aim of this guideline is to provide an update on evidence-based recommendations for treatment of adult patients with PsA. The previous BSR guidelines for PsA were published in 2012 and since that time, there have been many new advanced therapies licensed for PsA. This update will provide practical guidance for clinicians on the optimal selection of advanced therapies taking into account different domains of PsA (arthritis, enthesitis, dactylitis, axial disease and psoriasis) and key associated comorbidities. It will also update guidance on treatment strategy including the use of a treat-to-target approach. The guideline will be developed using the methods and processes outlined in Creating Clinical Guidelines: Our Protocol. (1) This development process to produce guidance, advice and recommendations for practice has National Institute for Health and Care Excellence (NICE) accreditation., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Thiopurines are widely used as maintenance therapy in inflammatory bowel disease (IBD) but the evidence base for their use is sparse and their role increasingly questioned. Using the largest series reported to date, we assessed the long-term effectiveness of thiopurines in ulcerative colitis (UC) and Crohn's disease (CD), including their impact on need for surgery., Design: Outcomes were assessed in 11 928 patients (4968 UC, 6960 CD) in the UK IBD BioResource initiated on thiopurine monotherapy with the intention of maintaining medically induced remission. Effectiveness was assessed retrospectively using patient-level data and a definition that required avoidance of escalation to biological therapy or surgery while on thiopurines. Analyses included overall effectiveness, time-to-event analysis for treatment escalation and comparison of surgery rates in patients tolerant or intolerant of thiopurines., Results: Using 68 132 patient-years of exposure, thiopurine monotherapy appeared effective for the duration of treatment in 2617/4968 (52.7%) patients with UC compared with 2378/6960 (34.2%) patients with CD (p<0.0001). This difference was corroborated in a multivariable analysis: after adjusting for variables including treatment era, thiopurine monotherapy was less effective in CD than UC (OR 0.47, 95% CI 0.43 to 0.51, p<0.0001). Thiopurine intolerance was associated with increased risk of surgery in UC (HR 2.44, p<0.0001); with a more modest impact on need for surgery in CD (HR=1.23, p=0.0015)., Conclusion: Thiopurine monotherapy is an effective long-term treatment for UC but significantly less effective in CD., Competing Interests: Competing interests: MP is in receipt of grant funding from Pfizer, Gilead and Roche, and has received speaker fees from Takeda. TR has received research/educational grants and/or speaker/consultation fees from Abbvie, BMS, Celgene, Ferring, Gilead, GSK, Mylan, LabGenius, Janssen, MSD, Novartis, Pfizer, Sandoz, Takeda and UCB., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: Patients with inflammatory bowel disease (IBD) have an excess burden of axial spondyloarthritis (axSpA), which, if left untreated, may significantly impact on clinical outcomes. We aimed to estimate the prevalence of axSpA, including previously undiagnosed cases, in IBD patients from studies involving cross-sectional imaging and identify the IBD features potentially associated with axSpA., Methods: PubMed, Embase and Cochrane databases were searched systematically between 1990 and 2018. Article reference lists and key conference abstract lists from 2012 to 2018 were also reviewed. All abstracts were reviewed by two authors to determine eligibility for inclusion. The study inclusion criteria were (a) adults aged 18 years or above, (b) a clinical diagnosis of IBD and (c) reporting identification of sacroiliitis using cross-sectional imaging., Results: A total of 20 observational studies were identified: 12 used CT, 6 used MR and 2 utilised both computed tomography (CT) and magnetic resonance (MR) imaging. Sample sizes ranged from 25 to 1247 (a total of 4096 patients); 31 studies were considered to have low selection bias, 13 included two or more radiology readers, and 3 included rheumatological assessments. The prevalence of sacroiliitis, the most commonly reported axSpA feature, ranged from 2.2% to 68.0% with a pooled prevalence of 21.0% [95% confidence interval (CI) 17-26%]. Associated IBD features include increasing IBD duration, increasing age, male sex, IBD location, inflammatory back pain and peripheral arthritis. No significant difference in the prevalence of sacroiliitis between Crohn's disease and ulcerative colitis was identified. Study limitations include variability in the individual study sample sizes and patient demographics., Conclusion: This review highlights the need for larger, well-designed studies using more sensitive imaging modalities and multivariable modelling to better estimate the prevalence of axSpA in IBD. An improved knowledge of the IBD phenotype(s) associated with axSpA and use of cross-sectional imaging intended for IBD assessment to screen for axSpA may help clinicians identify those patients most at risk., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)

SARS-CoV-2 has caused a global health crisis and mass vaccination programmes provide the best opportunity for controlling transmission and protecting populations. Despite the impressive clinical trial results of the BNT162b2 (Pfizer/BioNTech), ChAdOx1 nCoV-19 (Oxford/AstraZeneca), and mRNA-1273 (Moderna) vaccines, important unanswered questions remain, especially in patients with pre-existing conditions. In this position statement endorsed by the British Society of Gastroenterology Inflammatory Bowel Disease (IBD) section and IBD Clinical Research Group, we consider SARS-CoV-2 vaccination strategy in patients with IBD. The risks of SARS-CoV-2 vaccination are anticipated to be very low, and we strongly support SARS-CoV-2 vaccination in patients with IBD. Based on data from previous studies with other vaccines, there are conceptual concerns that protective immune responses to SARS-CoV-2 vaccination may be diminished in some patients with IBD, such as those taking anti-TNF drugs. However, the benefits of vaccination, even in patients treated with anti-TNF drugs, are likely to outweigh these theoretical concerns. Key areas for further research are discussed, including vaccine hesitancy and its effect in the IBD community, the effect of immunosuppression on vaccine efficacy, and the search for predictive biomarkers of vaccine success., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Biologics are now key drugs in the management of immune-mediated inflammatory diseases. However, the increasingly complex biologics environment and growing cost pressures in the UK have led to variability in drug commissioning and inequity of patient access across regions., Objectives: Our objectives were to provide consensus recommendations for enhancing the current situation in biologic prescribing in the UK by balancing clinical freedom with equitable distribution of biologics given the limited availability of resources., Methods: A modified Delphi approach was used to reach integrated, cross-specialty consensus among dermatologists, rheumatologists and gastroenterologists practising within the English National Health Service (NHS)., Results: We describe the concepts of clinical freedom and clinical judgement and demonstrate how, together with patient choice, they can be exercised in the context of biologic prescribing in the NHS. We highlight that in England, local variations occur that are at odds with National Institute for Health and Care Excellence (NICE) guidance; these variably limit the degree to which clinicians can exercise clinical freedom and impact on equity of patient access to treatments. We define factors encompassing a drug's value and identify challenges to the measurement and interpretation of this concept, which can raise barriers to the freedom of clinical choice and appropriate prescribing decisions allowing practices of holistic and personalised medicine. Cross-specialty consensus recommendations on ensuring equitable access to biologics in the NHS while protecting appropriate and individualised drug selection for patients are provided. We have also provided strategies for improving physician-commissioner communication to harmonise equity of patient access to biologics across England and improve patient outcomes. Commentary from patient advisory groups indicates that they welcome our exploration that value does not equal cost and agree that there should be an emphasis on shared decision making, which requires the clinician to practice clinical freedom by aligning the patient's needs and preferences with available treatment choices., Conclusions: This consensus highlights the need to strike a balance between clinical freedom and short-term cost restrictions to support equitable resource distribution within the English NHS. Consideration of these recommendations may help to harmonise local, regional and national services and balance equity of patient access to biologic treatments with excellence in the NHS.

Background and Aims: Faecal biomarkers, particularly calprotectin [FCAL], have become important diagnostic and monitoring tools in inflammatory bowel diseases [IBD]. As FCAL is mainly produced by neutrophils, we hypothesised that faecal lipocalin-2 [FLCN2], also expressed by intestinal epithelial cells [IEC], could be beneficial in specific clinical situations., Methods: We compared clinical and endoscopic activity-related correlations between FCAL and FLCN2, assayed from the same sample, in a cohort of 132 patients (72 Crohn's disease [CD]) and 40 controls. A detailed analysis of cellular origins was done by confocal microscopy and flow cytometry. To evaluate the potential to detect low-grade inflammation, we studied faecal and tissue concentrations in a cohort with clinical, endoscopic, and histological remission., Results: There was an excellent correlation between FCAL and FLCN2 [rS = 0.87, p <0.001] and comparable sensitivity and specificity to predict clinical and endoscopic disease activity, with optimal thresholds for endoscopic activity of 73.4 and 1.98 µg/g in ulcerative colitis [UC] and 78.4 and 0.56 µg/g in Crohn's disease for FCAL and FLCN2, respectively. Strong co-expression of both proteins was observed in granulocytes and macrophages. IECs expressed LCN2 but not CAL. In our IBD cohort in deep remission neither FCAL nor FLCN2 was different from controls; yet mucosal LCN2 but not CAL expressions remained elevated in the rectum of UC and the ileum of CD patients., Conclusions: This study corroborates the diagnostic equivalence of FLCN2 and FCAL in IBD. In remission, persistent mucosal overexpression renders LCN2 an attractive candidate for molecular inflammation warranting further investigation., (© 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.)

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 and study aims  Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has emerged as an important method for obtaining a preoperative tissue diagnosis for suspected cholangiocarcinoma. However, doubts remain about test sensitivity. This study assessed the value and limitations of EUS-FNA in clinical practice. Patients and methods  Patients undergoing EUS-FNA for biliary strictures/masses at a UK tertiary referral center from 2005 to 2014 were prospectively enrolled. Data on EUS-FNA findings, histology, and endoscopy and patient outcomes were collected to evaluate test performance and identify factors predictive of an inaccurate diagnostic result. Results  Ninety-seven patients underwent a total of 112 EUS-FNA procedures. Overall test sensitivity for an initial EUS-FNA for suspected cholangiocarcinoma was 75 % (95 % CI 64 %-84 %), with specificity 100 % (95 % CI 85 %-100 %) and negative predictive value 0.62 (95 % CI 0.47-0.75). Hilar lesions, the presence of a biliary stent, and a diagnosis of PSC were significantly independently associated with an inaccurate result. For the most difficult cases, repeat sampling and use of the Papanicolaou cytopathology grading scale led to an increase in test sensitivity from 17 % to 100 % ( P  = 0.015) with no loss of specificity. Conclusions  EUS-FNA was found to be a useful method for obtaining a preoperative tissue diagnosis for patients with suspected cholangiocarcinoma. This study identified markers that can reduce test accuracy and measures that can improve test performance of EUS-FNA., Competing Interests: Competing interests The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Objective: Management of acute severe UC (ASUC) during the novel COVID-19 pandemic presents significant dilemmas. We aimed to provide COVID-19-specific guidance using current British Society of Gastroenterology (BSG) guidelines as a reference point., Design: We convened a RAND appropriateness panel comprising 14 gastroenterologists and an IBD nurse consultant supplemented by surgical and COVID-19 experts. Panellists rated the appropriateness of interventions for ASUC in the context of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Median scores and disagreement index (DI) were calculated. Results were discussed at a moderated meeting prior to a second survey., Results: Panellists recommended that patients with ASUC should be isolated throughout their hospital stay and should have a SARS-CoV-2 swab performed on admission. Patients with a positive swab should be discussed with COVID-19 specialists. As per BSG guidance, intravenous hydrocortisone was considered appropriate as initial management; only in patients with COVID-19 pneumonia was its use deemed uncertain. In patients requiring rescue therapy, infliximab with continuing steroids was recommended. Delaying colectomy because of COVID-19 was deemed inappropriate. Steroid tapering as per BSG guidance was deemed appropriate for all patients apart from those with COVID-19 pneumonia in whom a 4-6 week taper was preferred. Post-ASUC maintenance therapy was dependent on SARS-CoV-2 status but, in general, biologics were more likely to be deemed appropriate than azathioprine or tofacitinib. Panellists deemed prophylactic anticoagulation postdischarge to be appropriate in patients with a positive SARS-CoV-2 swab., Conclusion: We have suggested COVID-19-specific adaptations to the BSG ASUC guideline using a RAND panel., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

The use of corticosteroids to treat patients with inflammatory bowel disease [IBD] has been the bedrock of IBD therapeutics since the pioneering work of Truelove and Witts in the UK in the 1950s and subsequent large cohort studies in the USA and Europe. Nevertheless, although effective for induction of remission, these agents do not maintain remission and are associated with a long list of recognised side effects, including a risk of increased mortality. With the arrival of an increasing number of therapies for patients with IBD, the question arises as to whether we are using these agents appropriately in contemporary practice. This review discusses the historical background to steroid usage in IBD, and also provides a brief review of the literature on side effects of corticosteroid treatment as relevant to IBD patients. Data on licensed medications are presented with specific reference to the achievement of corticosteroid-free remission. We review available international data on the incidence of corticosteroid exposure and excess, and discuss some of the observations we and others have made concerning health care and patient-level factors associated with the risk of corticosteroid exposure, including identification of 'at-risk' populations., (© 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.)

Inflammatory bowel disease (IBD) is a chronic inflammatory disease associated with increased risk of gastrointestinal cancers. We whole-genome sequenced 446 colonic crypts from 46 IBD patients and compared these to 412 crypts from 41 non-IBD controls from our previous publication on the mutation landscape of the normal colon. The average mutation rate of affected colonic epithelial cells is 2.4-fold that of healthy colon, and this increase is mostly driven by acceleration of mutational processes ubiquitously observed in normal colon. In contrast to the normal colon, where clonal expansions outside the confines of the crypt are rare, we observed widespread millimeter-scale clonal expansions. We discovered non-synonymous mutations in ARID1A, FBXW7, PIGR, ZC3H12A, and genes in the interleukin 17 and Toll-like receptor pathways, under positive selection in IBD. These results suggest distinct selection mechanisms in the colitis-affected colon and that somatic mutations potentially play a causal role in IBD pathogenesis., Competing Interests: Declaration of Interests C.A.A. is a paid consultant for Genomics plc and Bristol-Myers Squibb. All other authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Spondyloarthritis (SpA) may be regarded a family of auto-inflammatory conditions with inflammation focused on the joints. These form part of a wider family of immune-mediated inflammatory diseases, which include inflammatory bowel diseases (IBD). These conditions share common elements of pathophysiology and it is perhaps unsurprising, therefore, that individuals with SpA frequently manifest gastrointestinal inflammation, to which the physician managing the patient with SpA must be alert. In this article, we review the shared epidemiology and pathophysiology of these conditions, before discussing approaches to diagnosis and management of inflammatory gastrointestinal pathology in patients seen in rheumatology clinics. In particular, we discuss the difference between non-specific gastrointestinal inflammation commonly described in this patient group and the more specific diagnosis of Crohn's disease or ulcerative colitis. We describe the appropriate diagnostic workup for patients suspected of having IBD. In addition, we discuss how a diagnosis of IBD can inform treatment selection, highlighting important differences in treatment choice, drug dosing, monitoring and drug safety for this particular comorbid patient population., Competing Interests: Conflict of interest statement: TR has received research/educational grants and/or speaker/consultation fees from Abbvie, BMS, Celgene, Ferring, Gilead, GSK, LabGenius, Janssen, Mylan, MSD, Novartis, Pfizer, Sandoz, Takeda and UCB. CDJ: none relevant., (© The Author(s), 2020.)

Immune checkpoint inhibitors are a novel class of cancer treatment that have improved outcomes for a subset of cancer patients. They work by antagonising inhibitory immune pathways, thereby augmenting immune-mediated antitumour responses. However, immune activation is not cancer-specific and often results in the activation of immune cells in non-cancer tissues, resulting in off-target immune-mediated injury and organ dysfunction. Diarrhoea and gastrointestinal tract inflammation are common and sometimes serious side-effects of this type of therapy. Prompt recognition of gastrointestinal toxicity and, in many cases, rapid institution of anti-inflammatory or biologic therapy (or both) is required to reverse these complications. Management of organ-specific complications benefits from multidisciplinary input, including engagement with gastroenterologists for optimal management of immune checkpoint inhibitor-induced enterocolitis. In this British Society of Gastroenterology endorsed guidance document, we have developed a consensus framework for the investigation and management of immune checkpoint inhibitor-induced enterocolitis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To determine the challenges in diagnosis, monitoring, support provision in the management of inflammatory bowel disease (IBD) patients and explore the adaptations of IBD services., Methods: Internet-based survey by invitation of IBD services across the UK from 8 to 14 April 2020., Results: Respondents from 125 IBD services completed the survey. The number of whole-time equivalent gastroenterologists and IBD nurses providing elective outpatient care decreased significantly between baseline (median 4, IQR 4-7.5 and median 3, IQR 2-4) to the point of survey (median 2, IQR 1-4.8 and median 2, IQR 1-3) in the 6-week period following the onset of the COVID-19 pandemic (p<0.001 for both comparisons). Almost all (94%; 112/119) services reported an increase in IBD helpline activity. Face-to-face clinics were substituted for telephone consultation by 86% and video consultation by 11% of services. A variation in the provision of laboratory faecal calprotectin testing was noted with 27% of services reporting no access to faecal calprotectin, and a further 32% reduced access. There was also significant curtailment of IBD-specific endoscopy and elective surgery., Conclusions: IBD services in the UK have implemented several adaptive strategies in order to continue to provide safe and high-quality care for patients. National Health Service organisations will need to consider the impact of these changes in current service delivery models and staffing levels when planning exit strategies for post-pandemic IBD care. Careful planning to manage the increased workload and to maintain IBD services is essential to ensure patient safety., 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.)

Corticosteroids remain an important tool for inducing remission in inflammatory bowel disease (IBD) but they have no role in maintenance of remission. The significant adverse side effect profile of these drugs means their use should be avoided where possible or measures taken to reduce their risk. Despite an expanding array of alternative therapies, corticosteroid dependency and excess remain common. Appropriate steroid use is now regarded a key performance indicator in the management of IBD. This article aims to outline indications for corticosteroid use in IBD, their risks and strategies to reduce their use and misuse., Competing Interests: Competing interests: JB is supported by a grant provided by Crohn's and Colitis UK (grant number: SP2018/3). CS has received unrestricted research grants from Warner Chilcott, Janssen and AbbVie, has provided consultancy to Warner Chilcott, Falk, AbbVie, Takeda, Fresenius Kabi and Janssen, and had speaker arrangements with Warner Chilcott, Falk, AbbVie, MSD, Pfizer and Takeda. TR has received research/educational grants and/or speaker/consultation fees from Abbvie, BMS, Celgene, Ferring, Gilead, GSK, LabGenius, Janssen, Mylan, MSD, Novartis, Pfizer, Sandoz, Takeda and UCB GCP has received unrestricted grants from AbbVie and Takeda, has provided consultancy for AbbVie, Ferring, Takeda, Napp Pharmaceuticals, Janssen and Tillotts and has speaker arrangements with Ferring, Takeda, Janssen, AbbVie and Falk. RP is supported by funding from Wellcome Trust Institute Strategic Support Fund (ISSF) and Crohn's and Colitis UK grant. He has provided consultancy/ or speakers fees for Napp Pharmaceuticals and Falk. He has had educational grants from Pharmacosmos, Abbvie, Janssen, Warner-Chilcottand Takeda., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

This article is the second in a series of two publications relating to 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 previous guidelines., (Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends., Competing Interests: Competing interests: Conflicts of interest for authors and contributors are presented in online supplementary table 2., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patients with IBD are at risk of excess corticosteroids., Aims: To assess steroid excess in a large IBD cohort and test associations with quality improvement and prescribing., Methods: Steroid exposure was recorded for outpatients attending 19 centres and associated factors analysed. Measures taken to avoid excess were assessed., Results: Of 2385 patients, 28% received steroids in the preceding 12 months. 14.8% had steroid excess or dependency. Steroid use was significantly lower at 'intervention centres' which participated in a quality improvement programme (exposure: 23.8% vs 31.0%, P < .001; excess 11.5% vs 17.1%, P < .001). At intervention centres, steroid use fell from 2015 to 2017 (steroid exposure 30.0%-23.8%, P = .003; steroid excess 13.8%-11.5%, P = .17). Steroid excess was judged avoidable in 50.7%. Factors independently associated with reduced steroid excess in Crohn's disease included maintenance with anti-TNF agents (OR 0.61 [95% CI 0.24-0.95]), treatment in a centre with a multi-disciplinary team (OR 0.54 [95% CI 0.20-0.86]) and treatment at an intervention centre (OR 0.72 [95% CI 0.46-0.97]). Treatment with 5-ASA in CD was associated with higher rates of steroid excess (OR 1.72 [95% CI 1.24-2.09]). In ulcerative colitis (UC), thiopurine monotherapy was associated with steroid excess (OR 1.97 [95% CI 1.19-3.01]) and treatment at an intervention centre with less steroid excess (OR 0.72 [95% CI 0.45-0.95])., Conclusions: This study validates steroid assessment as a meaningful quality measure and provides a benchmark for this performance indicator in a large cohort. A programme of quality improvement was associated with lower steroid use., (© 2019 John Wiley & Sons Ltd.)

Background: Accelerated induction regimens of infliximab have been proposed to improve response rates in patients with steroid-refractory acute severe colitis., Aim: To determine the differences in outcome for acute severe ulcerative colitis between accelerated and standard-dose infliximab METHODS: We collected data on hospitalised patients receiving differing regimens of rescue therapy for steroid-refractory acute severe ulcerative colitis. Our primary outcome was 30-day colectomy rate. Secondary outcomes were colectomy within index admission, and at 90 days and 12 months. We used propensity score analysis with optimal calliper matching using high risk covariates defined a priori to reduce potential provider selection bias., Results: We included 131 patients receiving infliximab rescue therapy; 102 received standard induction and 29 received accelerated induction. In the unmatched cohort, there was no difference by type of induction in the 30-day colectomy rates (18% vs 20%, P = .45), colectomy during index admission (13% vs 20%, P = .26) or overall colectomy (20% vs 24%, P = .38). In the propensity score-matched cohort of 52 patients, 30-day colectomy (57% vs 27%, P = .048) and index admission colectomy (53% vs 23%, P = .045) rates were higher in those receiving standard induction compared to accelerated induction but there was no difference in overall colectomy rates (57% vs 31%, P = .09). There was no significant difference in length of stay or in complication and infection rates., Conclusion: In a propensity score-matched cohort, steroid-refractory acute severe ulcerative colitis patients, short-term, but not long-term, colectomy rates appear to be lower in those receiving an accelerated induction regimen., (© 2019 John Wiley & Sons Ltd.)

Introduction: Lack of comparative trial data on dosing regimens of infliximab in patients with acute severe ulcerative colitis (ASUC) failing intravenous corticosteroids has resulted in variability of rescue regimes in ASUC with potential impact on clinical outcomes. We aimed to evaluate practice variability and physician perspectives in decision-making with rescue therapy., Methodology: An internet-based survey of members of the inflammatory bowel disease (IBD) section of the British Society of Gastroenterology was conducted. The survey evaluated provider characteristics and general practice in the setting of ASUC, followed by a vignette with linked questions., Results: The response rate of the survey was 31% (209/682 IBD section members). 134 (78%) reported they would use standard infliximab dose (5 mg/kg) while 37 (22%) favoured a higher front-loading dose of 10 mg/kg citing low albumin, high C-reactive protein as their reason for their preference. IBD specialists chose the higher front-loading dose more often compared with other gastroenterologists (p=0.01) In the specific case vignette, accelerated induction (AI) was favoured by 51% of the respondents while 25% used the standard induction regime and 19% favoured colectomy. IBD specialists more often favoured AI compared with other gastroenterologists (p=0.03) with the main reason being presence of predictors of low infliximab levels (74%). The reasons cited for favouring standard induction (n=57) included lack of evidence for AI (18), their usual practice (11), unlicensed regime (7), and safety concerns (4)., Conclusions: There are significant variations in practice in the use of infliximab rescue therapies with an urgent need for development of care pathways to standardise practice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

This article reports on the sixth scientific workshop of the European Crohn's and Colitis Organisation [ECCO] on the pathogenesis of extraintestinal manifestations [EIMs] in inflammatory bowel disease [IBD]. This paper has been drafted by 15 ECCO members and 6 external experts [in rheumatology, dermatology, ophthalmology, and immunology] from 10 European countries and the USA. Within the workshop, contributors formed subgroups to address specific areas. Following a comprehensive literature search, the supporting text was finalized under the leadership of the heads of the working groups before being integrated by the group consensus leaders., (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.)

IL-12 and IL-23 are closely related cytokines with important roles in the regulation of tissue inflammation. Converging evidence from studies in mice, human observational studies and population genetics supports the importance of these cytokines in the regulation of mucosal inflammation in the gut in particular. Ustekinumab, a therapeutic antibody targeting both cytokines is now widely licensed for the treatment of Crohn's disease, including in Europe, the USA, Canada and Japan, whilst agents targeting IL-23 specifically are in late-phase clinical trials. We review the emerging understanding of the biology of IL-12 and IL-23, as well as that of their major downstream cytokines, including IL-17. In particular, we discuss how their biology has influenced the development of clinical trials and therapeutic strategies in IBD, as well as how findings from clinical trials, at times surprising, have in turn refocused our understanding of the underlying biology.

Introduction: Acute severe ulcerative colitis (ASUC) is a severe manifestation of ulcerative colitis (UC) that warrants hospitalisation. Despite significant advances in therapeutic options for UC and in the medical management of steroid-refractory ASUC, the initial treatment paradigm has not changed since 1955 and is based on the use of intravenous corticosteroids. This treatment is successful in approximately 50% of patients but failure of this and subsequent medical therapy still occurs, with colectomy rates of up to 40% reported. The I nterleukin 1 (IL-1) blockade in A cute S evere C o litis (IASO) trial aims to investigate whether antagonism of IL-1 signalling using anakinra in addition to intravenous corticosteroid treatment can improve outcomes in patients with ASUC., Methods and Analysis: IASO is a phase II, multicentre, two-arm (parallel group), randomised (1:1), placebo-controlled, double-blinded trial of short-duration anakinra in ASUC. Its primary outcome will be the incidence of medical (eg, infliximab/ciclosporin) or surgical rescue therapy (colectomy) within 10 days following the commencement of intravenous corticosteroid therapy. Secondary outcomes will include disease activity, time to clinical response, time to rescue therapy, colectomy incidence by day 98 post intravenous corticosteroids and safety. The trial aims to recruit 214 patients across 20 sites in the UK., Ethics and Dissemination: The trial has received approval from the Cambridge Central Research Ethics Committee (Ref: 17/EE/0347), the Health Research Authority (Ref: 201505) and Clinical Trials Authorisation from the Medicines and Healthcare products Regulatory Agency. We plan to present trial findings at scientific conferences and publish in high-impact peer-reviewed journals., Trial Registration Number: ISRCTN43717130; EudraCT 2017-001389-10., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Background: Vedolizumab (VDZ) is effective for treatment of ulcerative colitis (UC) and Crohn's disease (CD). In GEMINI trials, anti-tumor necrosis factor (anti-TNF)-naïve patients had a superior response compared with anti-TNF-exposed patients. In real-world experience (RWE), the number of included anti-TNF-naïve patients was low. We aimed to evaluate the effectiveness and safety of VDZ in anti-TNF-naïve patients in an RWE setting., Methods: This retrospective multicenter European pooled cohort study included consecutive active anti-TNF-naïve IBD patients treated with VDZ. The primary end point was clinical response at week 14. Patients with follow-up beyond week 14 and those discontinuing VDZ at any time were included for maintenance outcomes analysis., Results: Since January 2015, 184 anti-TNF-naïve patients from 23 centers initiated VDZ treatment (Crohn's disease [CD], 50; ulcerative colitis [UC], 134). In CD, 42/50 (82%) patients responded by week 14 and 32 (64%) were in clinical remission; 26/50 (52%) achieved corticosteroid-free remission (CSFR). At last follow-up (44 weeks; interquartile range [IQR], 30-52 weeks), 27/35 (77.1%) patients with available data responded to treatment; 24/35 (68.6%) were in clinical remission, 21/35 (60%) were in CSFR. For UC, 116/134 (79.1%) responded to treatment by week 14, including 53 (39.5%) in clinical remission; 49/134 (36.6%) achieved CSFR. At last follow-up (42.5 weeks; IQR, 30-52 weeks), 79/103 (76.7%) patients responded to treatment, 69/103 (67.0%) were in remission, and 61/103 (59.2%) were in CSFR. Adverse effects were reported in 20 (11%) of the patients, leading to treatment discontinuation in 6 (3.3%)., Conclusions: VDZ is similarly effective in ant-TNF-naïve CD and UC patients. The efficacy is higher than reported in anti-TNF-experienced patients and is comparable to that of anti-TNF biologics in this population.

We performed an updated meta-analysis incorporating the results of recent randomised controlled trials (RCTs) to measure the effectiveness of probiotic supplementation in preventing necrotising enterocolitis (NEC) and death in very low-birth-weight (VLBW) infants, and to investigate any differences in efficacy by probiotic agent. Using meta-regression analysis, we assessed the contribution of other measured variables on the overall effect size and between-study variability., Conclusion: Overall, probiotics lead to significant reductions in NEC incidence and mortality in VLBW infants. Differences in probiotic agents and the influence of prenatal steroids and feeding regimens may explain the differences in outcomes between studies., (©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Cytomegalovirus (CMV) is frequently detected in patients with ulcerative colitis (UC). The impact of CMV infection on the outcome of UC exacerbation remains unclear. The benefit of combining antiviral with anti-inflammatory treatment has not been evaluated yet. The aim of this study was to compare the outcome of CMV-positive hospitalized patients with UC treated with antiviral therapy either alone or combined with salvage anti-inflammatory therapy (infliximab [IFX] or cyclosporine A [CsA])., Methods: This was a multicenter retrospective study of hospitalized CMV-positive patients with UC. The patients were classified into 2 groups: antiviral-if treated with antivirals alone; combined-if treated with both antiviral and anti-inflammatory therapy. The outcomes included the rate of colectomy in both arms during the course of hospitalization and after 3/12 months., Results: A total of 110 patients were included; 47 (42.7%) patients did not receive IFX nor CsA; 36 (32.7%) received IFX during hospitalization or within 1 month before hospitalization; 20 (18.1%) patients received CsA during hospitalization; 7 (6.4%) were exposed to both IFX and CsA. The rate of colectomy was 14.5% at 30 days, 20.0% at 3 months, and 34.8% at 12 months. Colectomy rates were similar across treatment groups. No clinical and demographic variables were independently associated with the risk of colectomy., Conclusions: IFX or cyclosporine therapy is not associated with additional risk for colectomy over antiviral therapy alone in hospitalized CMV-positive patients with UC.

Anemia represents one of the most frequent complications in inflammatory bowel disease (IBD) and severely impairs the quality of life of affected patients. The etiology of anemia in IBD patients can be multifactorial, often involving a combination of iron deficiency (ID) and anemia of chronic disease (ACD). Although current guidelines recommend screening for and treatment of anemia in IBD patients, current observational data suggest that it still remains underdiagnosed and undertreated. Besides basic laboratory parameters (e.g. mean corpuscular volume, reticulocyte count, serum ferritin, transferrin saturation, etc.), the concentration of soluble transferrin receptor (sTfR) and novel parameters such as the sTfR/log ferritin index can guide the challenging task of differentiating between ID and ACD. Once identified, causes of anemia should be treated accordingly. This review summarizes our current understanding of anemia in IBD patients, including the underlying pathology, diagnostic approaches and appropriate anemia treatment regimens., Competing Interests: None

Single-nucleotide variations in C13orf31 (LACC1) that encode p.C284R and p.I254V in a protein of unknown function (called 'FAMIN' here) are associated with increased risk for systemic juvenile idiopathic arthritis, leprosy and Crohn's disease. Here we set out to identify the biological mechanism affected by these coding variations. FAMIN formed a complex with fatty acid synthase (FASN) on peroxisomes and promoted flux through de novo lipogenesis to concomitantly drive high levels of fatty-acid oxidation (FAO) and glycolysis and, consequently, ATP regeneration. FAMIN-dependent FAO controlled inflammasome activation, mitochondrial and NADPH-oxidase-dependent production of reactive oxygen species (ROS), and the bactericidal activity of macrophages. As p.I254V and p.C284R resulted in diminished function and loss of function, respectively, FAMIN determined resilience to endotoxin shock. Thus, we have identified a central regulator of the metabolic function and bioenergetic state of macrophages that is under evolutionary selection and determines the risk of inflammatory and infectious disease.