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Background and Aims: Despite intravenous (IV) vedolizumab being established for treatment of inflammatory bowel disease (IBD), the novel subcutaneous (SC) route of administration may provide numerous incentives to switch. However, large-scale real-world data regarding the long-term safety and effectiveness of this strategy are lacking., Methods: IBD patients on IV vedolizumab across 11 UK sites agreed to transition to SC injections or otherwise continued IV treatment. Data regarding clinical disease activity (Simple Clinical Colitis Activity Index, partial Mayo score, and modified Harvey-Bradshaw Index), biochemical markers (C-reactive protein and calprotectin), quality of life (IBD control), adverse events, treatment persistence, and disease-related outcomes (namely corticosteroid use, IBD-related hospitalization, and IBD-related surgery) were retrospectively collected from prospectively maintained clinical records at baseline and weeks 8, 24, and 52., Results: Data from 563 patients (187 [33.2%] Crohn's disease, 376 [66.8%] ulcerative colitis; 410 [72.8%] SC, 153 [27.2%] IV) demonstrated no differences in disease activity, remission rates, and quality of life between the SC and IV groups at all time points. Drug persistence at week 52 was similar (81.1% vs 81.2%; P = .98), as were rates of treatment alteration due to either active disease (12.2% vs 8.9%; P = .38) or adverse events (3.3% vs 6.3%; P = .41). At week 52, there were equivalent rates of adverse events (9.8% vs 7.8%; P = .572) and disease-related outcomes. IBD control scores were equivalent in both IV-IV and IV-SC groups., Conclusions: Switching to SC vedolizumab appears as effective, safe, and well tolerated as continued IV treatment and maintains comparable disease control and quality of life as IV treatment at 52 weeks., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: STARDUST, a phase 3b randomised trial, compared ustekinumab therapeutic strategies in patients with Crohn's disease (CD) using early endoscopic assessment and treat-to-target (T2T) versus standard of care (SoC)., Aim: To assess the efficacy of ustekinumab extended treatment in a long-term extension (LTE) of up to 104 weeks with dosing adapted according to clinical, biomarker and endoscopy outcomes., Methods: Adults with moderately-to-severely active CD received intravenous ustekinumab approximating 6 mg/kg at Week 0 and subcutaneous ustekinumab 90 mg at Week 8. At Week 16, 440 ≥70-point responders were randomised to T2T or SoC and 323 entered the LTE. At Week 48, a unified, protocol-defined ustekinumab dose frequency escalation/de-escalation was applied based on achieving endoscopic remission and corticosteroid-free clinical remission. Achieving corticosteroid-free clinical remission and biomarker remission at consecutive visits determined ustekinumab dosing frequency. Dichotomous variables were analysed using non-responder imputation., Results: Among patients who entered the LTE, 7.7%, 48.6% and 43.7% received doses every 4, 8 and 12 weeks, respectively. Ustekinumab dose frequency was escalated in 23.5% and de-escalated in 19.7%. Endoscopic response and remission rates were 28.9% and 10.73% (all randomised) and 39.3% and 14.6% (patients entering the LTE), respectively, at Week 104. Clinical remission a rates at week 104 were 50.2% (all randomised) and 68.4% (patients entering the LTE). There were no new safety signals., Conclusion: STARDUST LTE is the first interventional ustekinumab efficacy study to show a favourable benefit-risk profile with preservation of clinical and endoscopic outcomes through Week 104 using flexible, algorithm-driven dose adjustment including de-escalation., (© 2023 Janssen Pharmaceuticals and The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Scotland has a distinguished track record in foundational clinical research. From the completion of the first clinical trial undertaken in scurvy to cloning the world's first whole mammal, Scottish basic and clinical research is world leading. More recently, challenges in access to research skills, funding and programmes by clinical trainees led to the development of alternatives to these typical avenues of accessing research opportunities. Trainee networks evolved to meet the needs of trainees looking to access projects and collaboratives beyond audit and quality improvement commonly performed during structured training. These networks have enjoyed enormous success and have succeeded in progressing projects which have impactful outputs for patients, and improving clinical services. Here, we describe the foundation of the first pan-Scotland physician trainee research network; Scottish Trainees Research In Gastroterology and Hepatology (ScotRIGHT). We outline the foundational efforts, requisites and foundations required to develop a research network., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: STARDUST is a phase 3b randomized controlled trial comparing two ustekinumab treatment strategies in patients with Crohn's disease (CD): treat-to-target (T2T) versus standard of care (SoC)., Objective: We investigated the effect of a T2T or SoC ustekinumab treatment strategy on health-related quality of life (HRQoL) and work productivity and activity impairment (WPAI) over a 2-year follow-up period., Methods: At Week 16, adult patients with moderate-to-severe active CD were randomized 1:1 to either T2T or SoC treatment groups. We assessed changes from baseline in HRQoL measures (Inflammatory Bowel Disease Questionnaire [IBDQ], EuroQoL 5-dimension 5-level [visual analogue scale and index], Functional Assessment of Chronic Illness Therapy-Fatigue, Hospital Anxiety and Depression Scale-Anxiety and -Depression) and the WPAI questionnaire in two patient populations: randomized analysis set (RAS, patients randomized to either T2T or SoC at Week 16 and completed Week 48) and modified RAS (mRAS, patients who entered the long-term extension [LTE] period at Week 48)., Results: At Week 16, 440 patients were randomized to T2T (n = 219) or SoC (n = 221) arms; 366 patients completed Week 48. Of these, 323 patients entered the LTE and 258 patients completed 104 weeks of treatment. In the RAS population, percentages of patients achieving IBDQ response and remission were not significantly different between treatment arms at Weeks 16 and 48. In the overall mRAS population, IBDQ response and remission increased over time from Weeks 16-104. In both populations, improvements from baseline in all HRQoL measurements were observed at Week 16 and maintained until either Week 48 or Week 104, respectively. In both populations, improvements from baseline in T2T and SoC arms at Weeks 16, 48 or 104 in WPAI domains were observed., Conclusion: Independent of treatment strategy (T2T or SoC), ustekinumab was effective in improving HRQoL measurements and WPAI over a period of 2 years., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD)., Aim: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab., Results: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure., Conclusion: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure., (© 2022 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background and Aims: Carvedilol reduces rates of variceal bleeding and rebleeding by lowering portal pressure. However, an associated pleiotropic survival benefit has been proposed. We aimed to assess long-term survival in a cohort of patients previously randomised to receive either carvedilol or endoscopic band ligation (EBL) following oesophageal variceal bleeding (OVB)., Methods: The index study randomised 64 cirrhotic patients with OVB between 2006 and 2011 to receive either carvedilol or EBL. Follow-up was undertaken to April 2020 by review of electronic patient records. The primary outcome was survival. Other outcomes including variceal rebleeding and liver decompensation events were compared., Results: 26 out of 33 participants received carvedilol in the follow-up period and 28 out of 31 attended regular EBL sessions. The median number of follow-up days for all patients recruited was 1459 (SE = 281.74). On the intention to treat analysis, there was a trend towards improved survival in the carvedilol group (p = 0.09). On per-protocol analysis, carvedilol use was associated with improved long-term survival (p = 0.005, HR 3.083, 95% CI 1.397-6.809), fewer liver-related deaths (0% vs 22.57%, p = 0.013, OR ∞, 95%CI 1.565-∞) and fewer admissions with decompensated liver disease (12% vs 64.29%, p = 0.0002, OR 13.2, 95% CI 3.026-47.23) compared to the EBL group. There was no statistically significant difference in variceal rebleeding rates., Conclusion: Following OVB in cirrhotic patients, carvedilol use is associated with survival benefit, fewer liver-related deaths and fewer hospital admissions with decompensated liver disease. Further studies are needed to validate this finding., (© 2022 John Wiley & Sons Ltd.)

Background: A treat-to-target strategy, in which strictly defined treatment targets facilitate decision making in clinical practice, is advocated as an optimised management approach for some chronic disorders. The aim of the STARDUST trial was to assess whether a treat-to-target strategy with early endoscopy, regular biomarker and clinical symptom monitoring, and dose intensification for persistent inflammatory activity, was more successful in achieving endoscopic improvement at week 48 than a clinically driven maintenance strategy in patients with moderate-to-severe active Crohn's disease receiving ustekinumab., Methods: This open-label, multicentre, randomised phase 3b trial included adults with active, moderate-to-severe Crohn's disease (Crohn's Disease Activity Index [CDAI] 220-450 and Simple Endoscopic Score in Crohn's Disease [SES-CD] ≥3) for whom conventional therapy or one biologic therapy, or both, had failed. Patients received intravenous ustekinumab approximating 6 mg/kg at baseline and subcutaneous ustekinumab 90 mg at week 8. At week 16, patients with a CDAI improvement of 70 or more points from baseline were randomly assigned (1:1) to receive standard-of-care or treat-to-target maintenance treatment through week 48. Randomisation was balanced by using randomly permuted blocks and was stratified by biologic history status and baseline SES-CD score. All patients who signed informed consent, who were not screening failures, and who received at least one dose of study treatment were included in week 16 analyses. All patients included in week 16 analyses and randomly assigned to one of the maintenance treatment regimens were included in the week 48 efficacy and safety analyses (ie, on an intention-to-treat basis). Patients assigned to the treat-to-target arm received ustekinumab every 12 weeks or every 8 weeks based on SES-CD improvement from baseline and could escalate to every 4 weeks through week 48 if prespecified targets were missed. Patients assigned to the standard-of-care arm received ustekinumab every 12 weeks or every 8 weeks; those receiving treatment every 12 weeks could escalate per European labelling. The primary efficacy endpoint was endoscopic response at week 48 (SES-CD score ≥50% decrease from baseline), analysed by non-responder imputation. This trial is registered at ClinicalTrials.gov, NCT03107793, and is active but not recruiting., Findings: 498 patients received standard induction treatment, of whom 440 were randomly assigned to the treat-to-target group (n=219) or the standard-of-care group (n=221). At week 48, there was no significant difference in endoscopic response (83 [38%] of 219 patients vs 66 [30%] of 221 patients; p=0·087), endoscopic remission (25 [11%] vs 32 [15%]; p=0·334), mucosal healing (31 [14%] vs 37 [17%]; p=0·449), and clinical remission (135 [62%] vs 154 [70%]; p=0·072) between the two groups; clinical response was significantly lower in the treat-to-target group than in the standard-of-care group (149 [68%] vs 172 [78%]; p=0·020). Other endoscopic, clinical, and biomarker outcomes were generally not significantly different between groups. The most commonly reported treatment-emergent adverse events were nasopharyngitis (29 [13%] of 219 patients in the treat-to-target group vs 29 [13%] of 221 patients in the standard-of-care group), abdominal pain (23 [11%] vs 19 [9%]), arthralgia (24 [11%] vs 19 [9%]), and headache (24 [11%] vs 21 [10%])., Interpretation: Timely escalation of ustekinumab therapy for patients with Crohn's disease, based on early endoscopic response, clinical symptoms, and biomarkers, did not result in significantly better endoscopic outcomes at week 48 than symptom-driven decisions alone. Future studies need to confirm if some subgroups of patient might benefit from a treat-to-target strategy with ustekinumab., Funding: Janssen-Cilag., Competing Interests: Declaration of interests SD reports consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Dr Falk Pharma Eli Lilly, Enthera, Ferring Pharmaceuticals Inc, Gilead, Hospira, Inotrem, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB Inc, and Vifor; and reports payment for expert testimony from AbbVie, Amgen, Ferring Pharmaceuticals Inc, Gilead, Janssen, Mylan, Pfizer, and Takeda. SV reports grants or contracts from AbbVie, Johnson & Johnson, Pfizer, Galapagos, and Takeda; consulting fees from AbbVie, AbolerIS Pharma, AgomAb, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Avaxia, BMS, Boehringer Ingelheim, Celgene, CVasThera, Dr Falk Pharma, Ferring, Galapagos, Genentech/Roche, Gilead, GlaxoSmithKline, Hospira, Imidomics, Janssen, Johnson & Johnson, Lilly, Materia Prima, MiroBio, Morphic, MrMHealth, MSD, Mundipharma, Pfizer Inc, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillots Pharma AG, and Zealand Pharma; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or education events from AbbVie, Alimentiv, Boehringer Ingelheim, Celgene, Dr Falk Pharma, Ferring, Galapagos, Genentech/Roche, Gilead, GlaxoSmithKline, Janssen, Johnson & Johnson, Pfizer, Takeda, and Tillots Pharma AG. GD'H reports consulting fees from AbbVie, Alimentiv, Arena, AstraZenea, Bristol Myer Squibb, Boehringer Ingelheim, Eli Lilly, Exeliom, Gossamer Bio, Johnson & Johnson, Pfizer, Prometheus, and Protagonist; and payment of honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Bristol Myer Squibb, Johnson & Johnson, and Pfizer. JP reports research grants from AbbVie and Pfizer; consulting fees from AbbVie, Arena, Athos, Boehringer Ingelheim, Celgene, Galapagos, Genentech/Roche, GlaxoSmithKline, Janssen, Mirum, Morphic, Nestle, Origo, Pandion, Pfizer, Progenity, Protagonist, Takeda, Theravance, and Wassermann; reports payment for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Janssen, Pfizer, Roche, and Takeda; participation on a Data Safety Monitoring Board or Advisory Board for Alimentiv; and has owner stock options in Oppilan. AD reports consultancy fees from AbbVie, Amgen, BMS/Celgene, Boehringer-Ingelheim, Celltrion, Dr Falk Pharma, Ferring, Fresenius Kabi, Galapagos, Gilead, Janssen, MSD, Lilly, Pfizer, Pharmacosmos, Roche, Takeda, Tillotts, and Vifor; payment for lectures, presentations, speakers bureaus, manuscript writing, or educational events for AbbVie, Falk Foundation, Ferring, Immunowissen.tv, Janssen, Lilly, Med Update GmbH, MSD, Pfizer, Pharmacosmos, Streamed Up, Takeda, Thieme-Verlag, Tillotts, and Vifor. FM has served as a speaker and received honoraria from Merck Sharp & Dohme, AbbVie, Vifor, Falk, Laboratórios Vitória, Ferring, Hospira, and Biogen. MN is an employee of Janssen-Cilag, Polska Sp. z o.o and has stocks or stock options in Johnson & Johnson. MLB is an employee of Janssen-Cilag, France and has stocks or stock options in Janssen. FL is an employees of Janssen-Cilag, France and has restricted share units from Johnson & Johnson. MLa is an employee of Janssen-Cilag, B.V. and has restricted stocks in Janssen. LN is an employee of Janssen-Cilag, Russia. IB is an employee of Janssen-Cilag, Italy. MD reports consulting fees from Bioclinica; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Janssen, Pfizer, Roche, and Takeda; and support for attending meetings and/or travel from AbbVie, Chiesi, Janssen, Mundifarma, SOFAR, Roche, and Takeda. MLu reports no competing interests. AA reports consultancy fees from AbbVie, Allergan, Amgen, Arena, Biogen, Bristol-Myers Squibb, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mylan, Pfizer, Roche, Samsung Bioepis, Sandoz, and Takeda; payment or honoraria for lecture, presentations, speakers bureaus, manuscript writing, or education events from AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, and Tigenix; research grants from MSD, Takeda, and Pfizer; and support for attending meetings and/or travel from AbbVie, Janssen, Pfizer, and Takeda. MLö has received a research grant from Galapagos and consulting fees from Alimentiv, Bristol Myers Squibb, Galapagos, Gilead, Takeda, and Tillotts. DRG reports consulting fees from Galapagos and Pfizer; payment or honoraria for lectures from AbbVie and Pfizer; and support for attending meetings and travel from AbbVie, Ferring, Janssen, and Tillots. LP-B reports grants or contracts from AbbVie, Fresenius Kabi, MSD, and Takeda; consulting fees from Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Pharmacosmos, Celltrion, Takeda, Boerhinger Ingelheim, Pfizer, Index Pharmaceuticals, Sandoz, Celgene, Biogen, Samsung Bioepis, Alma, Sterna, Nestle, Inotrem, Enterome, Allergan, MSD, Roche, Arena, Gilead, Hikma, Amgen, BMS, Vifor, Norgine, Mylan, Lilly, Fresenius Kabi, Oppilan Pharma, Sublimity Therapeutics, Applied Molecular Transport, OSE Immunotherapeutics, Enthera, Theravance, and Pandion Therapeutics; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Galapagos, Janssen, Ferring, Tillots, Pharmacosmos, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Arena, Gilead, Hikma, Amgen, and Vifor; support for attending meeting and/or travel from AbbVie, Galapagos, Janssen, Ferring, Tillots, Pharmacosmos, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Arena, Gilead, Hikma, Amgen, and Vifor; participation on a Data Safety Monitoring Board or Advisory Board for Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Pharmacosmos, Celltrion, Takeda, Boerhinger Ingelheim, Pfizer, Index Pharmaceuticals, Sandoz, Celgene, Biogen, Samsung Bioepis, Alma, Sterna, Nestle, Inotrem, Enterome, Allergan, MSD, Roche, Arena, Gilead, Hikma, Amgen, BMS, Vifor, Norgine, Mylan, Lilly, Fresenius Kabi, Oppilan Pharma, Sublimity Therapeutics, Applied Molecular Transport, OSE Immunotherapeutics, Enthera, Theravance, and Pandion Therapeutics; and stock or stock options in CTMA., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: It has been suggested that the gut microbiome of patients with inflammatory bowel disease (IBD) is unable to ferment dietary fibre. This project explored the in vitro effect of fibre fermentation on production of short-chain fatty acids (SCFA) and on microbiome composition. Methods: Faecal samples were collected from 40 adults (>16 y) with IBD (n = 20 with Crohn’s disease and n = 20 with ulcerative colitis) in clinical remission and 20 healthy controls (HC). In vitro batch culture fermentations were carried out using as substrates maize starch, apple pectin, raftilose, wheat bran, α cellulose and a mixture of these five fibres. SCFA concentration (umol/g) was quantified with gas chromatography and microbiome was profiled with 16S rRNA sequencing. Results: Fibre fermentation did not correct the baseline microbial dysbiosis or lower diversity seen in either patients with CD or UC. For all fibres, up to 51% of baseline ASVs or genera changed in abundance in HC. In patients with IBD, fermentation of fibre substrates had no effect on species or genera abundance. Production of SCFA varied among the different fibre substrates but this was not different between the two IBD groups and compared to HC after either 5 or 24 h fermentation. Conclusions: Despite extensive microbial dysbiosis, patients with IBD have a similar capacity to ferment fibre and release SCFA as HC. Fibre supplementation alone may be unlikely to restore to a healthy status the compositional shifts characteristic of the IBD microbiome.

Objective: To evaluate the impact of structured transition from pediatric to adult inflammatory bowel disease (IBD) services on objective patient outcomes, including disease flares, admission rates, and healthcare resource use., Methods: A retrospective observational study in 11 United Kingdom gastroenterology centers. Transition patients attended ≥2 visits to the gastroenterology service with both pediatric and adult personnel jointly present; non-transition patients transferred to adult services without joint visits. Data were collected from medical records for the 12-month periods before and after the date of the first visit involving adult IBD services (index visit)., Results: A total of 129 patients were included: 95 transition patients and 34 non-transition patients. In the 12 months post-index visit, transition patients had fewer disease flares (P  = 0.05), were more likely to be steroid-free (71% vs 41%, P < 0.05), and were less likely to have an emergency department visit leading to hospital admission (5% vs 18%, P < 0.05). During this period, the mean estimated overall cost of care per patient was £1644.22 in the transition group and £1827.32 in the non-transition group (P = 0.21)., Conclusion: Structured transition from pediatric to adult IBD care services was associated with positive and cost-neutral outcomes in patients with pediatric IBD., Competing Interests: Conflicts of Interest: S.M. has received honoraria for previous advisory board/meeting participation from AbbVie; and has served as a speaker, a consultant, and an advisory board member for AbbVie, Actavis, Falk, Ferring, Janssen, MSD, and Takeda. J.O.L. has served as a speaker, a consultant, and an advisory board member for AbbVie, Actavis, Ferring, Hospira, Janssen, MSD, Napp, Pfizer, Shire, Takeda, and Tillotts Pharma; and has received research funding from Hospira, MSD, and Shire. R.K.R. has served as a speaker, a consultant, and an advisory board member for AbbVie, Janssen, Pharmacosmos, Takeda, and Tillotts Pharma. D.R.G. has spoken/worked in an advisory capacity for AbbVie, Ferring, MSD, Takeda, and Vifor Pharma. I.S. has received honoraria for previous speaking/advisory board membership from AbbVie. C.D.M. has served as a speaker, a consultant, and an advisory board member for AbbVie, Falk, MSD, and Shire. T.F.-H. is an employee of AbbVie and may own AbbVie stock and/or options. S.S. has received research grants from Amgen, Ferring, MSD, Pfizer, Takeda, Tillotts Pharma, and Warner Chilcott; and has received sponsorship and advisory board and speaker honoraria from AbbVie, Celgene, Falk, Ferring, Janssen, MSD, Pfizer, Pharmacosmos, Takeda, and Warner Chilcott., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

To understand the contribution of mononuclear phagocytes (MNP), which include monocyte-derived intestinal macrophages, to the pathogenesis of inflammatory bowel disease (IBD), it is necessary to identify functionally-different MNP populations. We aimed to characterise intestinal macrophage populations in patients with IBD. We developed 12-parameter flow cytometry protocols to identify and human intestinal MNPs. We used these protocols to purify and characterize colonic macrophages from colonic tissue from patients with Crohn's disease (CD), ulcerative colitis (UC), or non-inflamed controls, in a cross-sectional study. We identify macrophage populations (CD45 + CD64 + HLA-DR + ) and describe two distinct subsets, differentiated by their expression of the mannose receptor, CD206. CD206 + macrophages expressed markers consistent with a mature phenotype: high levels of CD68 and CD163, higher transcription of IL-10 and lower expression of TREM1. CD206 - macrophages appear to be less mature, with features more similar to their monocytic precursors. We identified and purified macrophage populations from human colon. These appear to be derived from a monocytic precursor with high CCR2 and low CD206 expression. As these cells mature, they acquire expression of IL-10, CD206, CD63, and CD168. Targeting the newly recruited monocyte-derived cells may represent a fruitful avenue to ameliorate chronic inflammation in IBD., (© 2021. The Author(s).)

Background: Advances in multi-modality treatment of locally advanced rectal cancer (LARC) have resulted in low local recurrence rates, but around 30% of patients will still die from distant metastatic disease. In parallel, there is increasing recognition that with radiotherapy and systemic treatment, some patients achieve a complete response and may avoid surgical resection, including in many cases, the need for a permanent stoma. Extended neoadjuvant regimes have emerged to address these concerns. The inclusion of immunotherapy in the neoadjuvant setting has the potential to further enhance this strategy by priming the local immune microenvironment and engaging the systemic immune response., Methods: PRIME-RT is a multi-centre, open label, phase II, randomised trial for patients with newly diagnosed LARC. Eligible patients will be randomised to receive either: short course radiotherapy (25 Gray in 5 fractions over one week) with concomitant durvalumab (1500 mg administered intravenously every 4 weeks), followed by FOLFOX (85 mg/m 2 oxaliplatin, 350 mg folinic acid and 400 mg/m 2 bolus 5-fluorouracil (5-FU) given on day 1 followed by 2400 mg/m 2 5-FU infusion over 46-48 h, all administered intravenously every 2 weeks), and durvalumab, or long course chemoradiotherapy (50 Gray to primary tumour in 25 fractions over 5 weeks with concomitant oral capecitabine 825 mg/m 2 twice per day on days of radiotherapy) with durvalumab followed by FOLFOX and durvalumab. The primary endpoint is complete response rate in each arm. Secondary endpoints include treatment compliance, toxicity, safety, overall recurrence, proportion of patients with a permanent stoma, and survival. The study is translationally rich with collection of bio-specimens prior to, during, and following treatment in order to understand the molecular and immunological factors underpinning treatment response. The trial opened and the first patient was recruited in January 2021. The main trial will recruit up to 42 patients with LARC and commence after completion of a safety run-in that will recruit at least six patients with LARC or metastatic disease., Discussion: PRIME-RT will explore if adding immunotherapy to neoadjuvant radiotherapy and chemotherapy for patients with LARC can prime the tumour microenvironment to improve complete response rates and stoma free survival. Sequential biopsies are a key component within the trial design that will provide new knowledge on how the tumour microenvironment changes at different time-points in response to multi-modality treatment. This expectation is that the trial will provide information to test this treatment within a large phase clinical trial. Trial registration Clinicaltrials.gov NCT04621370 (Registered 9th Nov 2020) EudraCT number 2019-001471-36 (Registered 6th Nov 2020)., (© 2021. The Author(s).)

Musculoskeletal deficits are among the most commonly reported extra-intestinal manifestations and complications of inflammatory bowel disease (IBD), especially in those with Crohn's disease. The adverse effects of IBD on bone and muscle are multifactorial, including the direct effects of underlying inflammatory disease processes, nutritional deficits, and therapeutic effects. These factors also indirectly impact bone and muscle by interfering with regulatory pathways. Resultantly, individuals with IBD are at increased risk of osteoporosis and sarcopenia and associated musculoskeletal morbidity. In paediatric IBD, these factors may contribute to suboptimal bone and muscle accrual. This review evaluates the main pathogenic factors associated with musculoskeletal deficits in children and adults with IBD and summarises the current literature and understanding of the musculoskeletal phenotype in these patients.

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 and Aims: ESPEN guidelines advocate patients with inflammatory bowel disease (IBD) have their micronutrient levels checked regularly. This study described the micronutrient status of patients with quiescent IBD and explores whether biochemical micronutrient deficiencies related to time to subsequent disease relapse., Methods: Sixteen micronutrients were measured prospectively in blood of patients with IBD in clinical remission [Harvey Bradshaw Index (HBI) ≤4 in Crohn's disease (CD) and a partial Mayo score <2 in ulcerative colitis (UC)]. Patients were followed prospectively using the electronic patient records. The ability of micronutrient status to predict time to relapse was tested with survival analysis and Cox regression., Results: Ninety-three patients were enrolled; Fifty (54%) were also in biochemical remission defined as a normal faecal calprotectin (<250 μg/g), C-reactive protein (<10 mg/L) and serum albumin (>35 g/L). Deficiencies in vitamin D were identified in 27 (29%), zinc in 15 (16%), vitamin B6 in 13 (14%), vitamin C in 12 (13%) and vitamin B12 in 10 (11%). Fewer participants had low serum folate 7 (8%), ferritin 8 (9%), copper 4 (4%), magnesium 4 (4%) and plasma selenium 3 (3%). Zinc deficiency was predictive of a shorter time to subsequent relapse (HR: 6.9; 95%CI [1.9 to 26], p = 0.008); in sub analysis of those with CD this effect was even more profound (p = 0.001)., Conclusion: We identified biochemical deficiencies for several micronutrients among adults with IBD clinically in remission. We have also highlighted a significant association between zinc deficiency and time to subsequent disease relapse in patients with CD which needs further investigation., Competing Interests: Conflict of interest KG received research grants and speakers’ fees from Nestle Health Science and Nutricia-Danone outside of this work; The rest of the authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Muscle-bone deficits are common in pediatric Crohn's disease; however, few studies have assessed long-term musculoskeletal outcomes in adults with childhood-onset Crohn's disease. This study assessed the prevalence of musculoskeletal deficits in young adults with childhood-onset Crohn's disease compared with healthy controls., Methods: High-resolution MRI and MR spectroscopy were used to assess bone microarchitecture, cortical geometry and muscle area, and adiposity at distal femur and bone marrow adiposity (BMA) at lumbar spine. Muscle function and biomarkers of the muscle-bone unit were also assessed., Results: Twenty-seven adults with Crohn's disease with median (range) age 23.2 years (18.0, 36.1) and 27 age and sex-matched controls were recruited. Trabecular microarchitecture, cortical geometry and BMA were not different between Crohn's disease and controls (P > 0.05 for all). Muscle area was lower (P = 0.01) and muscle fat fraction was higher (P = 0.04) at the distal femur in Crohn's disease compared to controls. Crohn's disease participants had lower grip strength [-4.3 kg (95% confidence interval (CI), -6.8 to -1.8), P = 0.001] and relative muscle power [-5.0 W/kg (95% CI, -8.8 to -1.2), P = 0.01]. Crohn's disease activity scores negatively associated with trabecular bone volume (r = -0.40, P = 0.04) and muscle area (r = -0.41, P = 0.03)., Conclusion: Young adults with well-controlled Crohn's disease managed with contemporary therapies did not display abnormal bone microarchitecture or geometry at the distal femur but exhibited muscle deficits. The observed muscle deficits may predispose to musculoskeletal morbidity in future and interventions to improve muscle mass and function warrant investigation.

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.)

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.)

Background: Exclusive enteral nutrition (EEN) is an effective treatment for Crohn's disease., Aims: To investigate the hypothesis that ingredients of EEN formulas are unlikely to initiate a disease flare and that their dietary elimination is not essential for disease amelioration., Methods: We performed compositional analysis of EEN formulas with evidence of efficacy in management of active Crohn's disease. Macronutrient content was compared against the dietary reference values (DRV), the UK National Diet and Nutrition Survey (NDNS) and intake of Crohn's disease children. Food additives were cross-referenced against the FAO/WHO database., Results: Sixty-one formulas were identified with variable composition (carbohydrates [22.8%-89.3%], protein [7.8%-30.1%], fat [0%-52.5%]). Maltodextrin, milk protein and vegetable/plant oils were the commonest macronutrient sources. Their n-6:n-3 fatty acid ratio varied from 0.25 to 46.5. 56 food additives were identified (median per formula: 11). All formulas were lactose-free, gluten-free, and 82% lacked fibre. The commonest food additives were emulsifiers, stabilisers, antioxidants, acidity regulators and thickeners. Food additives, implicated in Crohn's disease aetiology, were present in formulas (modified starches [100%], carrageenan [22%], carboxymethyl cellulose [13%] and polysorbate 80 [5%]). Remission rates did not differ between EEN formulas with and without those food additives. Analysis including only formulas from randomised controlled trials (RCTs) retained in the latest Cochrane meta-analysis produced similar findings. EEN formulas contained less energy from saturated fat than NDNS intake., Conclusion: We have identified food ingredients which are present in EEN formulas that are effective in Crohn's disease and challenge perceptions that these ingredients might be harmful., (© 2020 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

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.)

Inflammatory bowel disease (IBD) is a debilitating chronic inflammatory disease of the gastrointestinal (GI) tract. It affects more than 3.5 million people in the western world and places a huge financial burden on healthcare systems. IBD is highly heterogeneous; disease severity and outcomes in IBD are highly variable, and patients may experience episodes of relapse and remission. However, treatment often follows a step-up model whereby the patients start with anti-inflammatory agents (corticosteroids or immunosuppressants) and step-up to monoclonal anti-tumour necrosis factor-α (TNFα) antibodies and then other biologics if the initial drugs cannot control disease. Unfortunately, many patients do not respond to the costly biologics, and thus often still require gut-resective surgery, which decreases quality of life. In order to decrease rates of surgery and ineffective treatments, it is important to identify markers that accurately predict disease progression and treatment responses, to inform decisions about the best choice of therapeutics. Here we examine molecular approaches to patient stratification that aim to increase the effectiveness of treatments and potentially reduce healthcare costs. In the future, it may become possible to stratify patients based on their suitability for specific molecular-targeted therapeutic agents, and eventually use molecular stratification for personalised medicine in IBD., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background & Aims: Vedolizumab is an anti-a4b7 monoclonal antibody that is licensed for the treatment of moderate to severe Crohn's disease and ulcerative colitis. The aims of this study were to establish the real-world effectiveness and safety of vedolizumab for the treatment of inflammatory bowel disease., Methods: This was a retrospective study involving seven NHS health boards in Scotland between June 2015 and November 2017. Inclusion criteria included: a diagnosis of ulcerative colitis or Crohn's disease with objective evidence of active inflammation at baseline (Harvey-Bradshaw Index[HBI] ≥5/Partial Mayo ≥2 plus C-reactive protein [CRP] >5 mg/L or faecal calprotectin ≥250 µg/g or inflammation on endoscopy/magnetic resonance imaging [MRI]); completion of induction; and at least one clinical follow-up by 12 months. Kaplan-Meier survival analysis was used to establish 12-month cumulative rates of clinical remission, mucosal healing, and deep remission [clinical remission plus mucosal healing]. Rates of serious adverse events were described quantitatively., Results: Our cohort consisted of 180 patients with ulcerative colitis and 260 with Crohn's disease. Combined median follow-up was 52 weeks (interquartile range [IQR] 26-52 weeks). In ulcerative colitis, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 57.4%, 47.3%, and 38.5%, respectively. In Crohn's disease, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 58.4%, 38.9%, and 28.3% respectively. The serious adverse event rate was 15.6 per 100 patient-years of follow-up., Conclusions: Vedolizumab is a safe and effective treatment for achieving both clinical remission and mucosal healing in ulcerative colitis and Crohn's disease., (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.)

Background: Anti-TNF drugs are effective treatments for the management of Crohn's disease but treatment failure is common. We aimed to identify clinical and pharmacokinetic factors that predict primary non-response at week 14 after starting treatment, non-remission at week 54, and adverse events leading to drug withdrawal., Methods: The personalised anti-TNF therapy in Crohn's disease study (PANTS) is a prospective observational UK-wide study. We enrolled anti-TNF-naive patients (aged ≥6 years) with active luminal Crohn's disease at the time of first exposure to infliximab or adalimumab between March 7, 2013, and July 15, 2016. Patients were evaluated for 12 months or until drug withdrawal. Demographic data, smoking status, age at diagnosis, disease duration, location, and behaviour, previous medical and drug history, and previous Crohn's disease-related surgeries were recorded at baseline. At every visit, disease activity score, weight, therapy, and adverse events were recorded; drug and total anti-drug antibody concentrations were also measured. Treatment failure endpoints were primary non-response at week 14, non-remission at week 54, and adverse events leading to drug withdrawal. We used regression analyses to identify which factors were associated with treatment failure., Findings: We enrolled 955 patients treated with infliximab (753 with originator; 202 with biosimilar) and 655 treated with adalimumab. Primary non-response occurred in 295 (23·8%, 95% CI 21·4-26·2) of 1241 patients who were assessable at week 14. Non-remission at week 54 occurred in 764 (63·1%, 60·3-65·8) of 1211 patients who were assessable, and adverse events curtailed treatment in 126 (7·8%, 6·6-9·2) of 1610 patients. In multivariable analysis, the only factor independently associated with primary non-response was low drug concentration at week 14 (infliximab: odds ratio 0·35 [95% CI 0·20-0·62], p=0·00038; adalimumab: 0·13 [0·06-0·28], p<0·0001); the optimal week 14 drug concentrations associated with remission at both week 14 and week 54 were 7 mg/L for infliximab and 12 mg/L for adalimumab. Continuing standard dosing regimens after primary non-response was rarely helpful; only 14 (12·4% [95% CI 6·9-19·9]) of 113 patients entered remission by week 54. Similarly, week 14 drug concentration was also independently associated with non-remission at week 54 (0·29 [0·16-0·52] for infliximab; 0·03 [0·01-0·12] for adalimumab; p<0·0001 for both). The proportion of patients who developed anti-drug antibodies (immunogenicity) was 62·8% (95% CI 59·0-66·3) for infliximab and 28·5% (24·0-32·7) for adalimumab. For both drugs, suboptimal week 14 drug concentrations predicted immunogenicity, and the development of anti-drug antibodies predicted subsequent low drug concentrations. Combination immunomodulator (thiopurine or methotrexate) therapy mitigated the risk of developing anti-drug antibodies (hazard ratio 0·39 [95% CI 0·32-0·46] for infliximab; 0·44 [0·31-0·64] for adalimumab; p<0·0001 for both). For infliximab, multivariable analysis of immunododulator use, and week 14 drug and anti-drug antibody concentrations showed an independent effect of immunomodulator use on week 54 non-remission (odds ratio 0·56 [95% CI 0·38-0·83], p=0·004)., Interpretation: Anti-TNF treatment failure is common and is predicted by low drug concentrations, mediated in part by immunogenicity. Clinical trials are required to investigate whether personalised induction regimens and treatment-to-target dose intensification improve outcomes., Funding: Guts UK, Crohn's and Colitis UK, Cure Crohn's Colitis, AbbVie, Merck Sharp and Dohme, Napp Pharmaceuticals, Pfizer, and Celltrion., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background & Aims: Exclusive enteral nutrition (EEN) is the only established dietary treatment for Crohn's disease (CD), but its acceptability is limited. There is a need for novel dietary treatments for CD., Methods: We evaluated the effects of an individualized food-based diet (CD-TREAT), with similar composition to EEN, on the gut microbiome, inflammation, and clinical response in a rat model, healthy adults, and children with relapsing CD. Twenty-five healthy adults randomly received EEN or CD-TREAT for 7 days, followed by a 14-day washout period, followed by the alternate diet. Fecal microbiome and metabolome were assessed before and after each diet. HLA-B7 and HLA-B27 transgenic rats with gut inflammation received EEN, CD-TREAT, or standard chow for 4 weeks. Fecal, luminal, and tissue microbiome, fecal metabolites, and gut inflammation were assessed. Five children with active CD activity received CD-TREAT and their clinical activity and calprotectin were evaluated after 8 weeks of treatment., Results: For healthy adults, CD-TREAT was easier to comply with and more acceptable than EEN. CD-TREAT induced similar effects to EEN (EEN vs CD-TREAT) on fecal microbiome composition, metabolome, mean total sulfide (increase 133.0 ± 80.5 vs 54.3 ± 47.0 nmol/g), pH (increase 1.3 ± 0.5 vs 0.9 ± 0.6), and the short-chain fatty acids (μmol/g) acetate (decrease 27.4 ± 22.6 vs 21.6 ± 20.4), propionate (decrease 5.7 ± 7.8 vs 5.2 ± 7.9), and butyrate (decrease 7.0 ± 7.4 vs 10.2 ± 8.5). In the rat model, CD-TREAT and EEN produced similar changes in bacterial load (decrease 0.3 ± 0.3 log 10 16S rRNA gene copies per gram), short-chain fatty acids, microbiome, and ileitis severity (mean histopathology score decreases of 1.25 for EEN [P = .015] and 1.0 for CD-TREAT [P = .044] vs chow). In children receiving CD-TREAT, 4 (80%) had a clinical response and 3 (60%) entered remission, with significant concurrent decreases in fecal calprotectin (mean decrease 918 ± 555 mg/kg; P = .002)., Conclusion: CD-TREAT replicates EEN changes in the microbiome, decreases gut inflammation, is well tolerated, and is potentially effective in patients with active CD. ClinicalTrials.gov, numbers NCT02426567 and NCT03171246., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Results from clinical trials show that vedolizumab is an efficacious treatment for inflammatory bowel disease, namely Crohn's disease (CD) and ulcerative colitis (UC). However, there is limited evidence from real-world clinical practice, especially on early clinical experiences in the UK.To describe real-world early experiences of vedolizumab to treat CD and UC in the UK.A retrospective, chart review study of patients with CD or UC treated with vedolizumab across 5 UK hospitals. All eligible adults (≥18 years at initiation) with a diagnosis of CD and ≥14 weeks of data or UC and ≥10 weeks of data available following vedolizumab initiation were included.Data were analyzed for 112 patients (CD: 66; UC: 46). Patients with CD had a median of 7.4 (interquartile range 5.7-9.4) months follow-up and patients with UC had a median of 7.4 (5.6-10.2) months follow-up post-vedolizumab initiation. Most patients, 80% (53/66) with CD and 89% (41/46) with UC, remained on vedolizumab treatment at the time of data collection. No new safety signals were identified during the study.These results add to the body of evidence supporting vedolizumab as an effective and well-tolerated treatment for CD and UC in real-world clinical practice.