Tofacitinib versus Vedolizumab Among Bio-naïve Patients with Ulcerative Colitis: A Real-World Propensity-Weighted Comparison.

Background And Aims: Over the last decade, treatment options for moderate-to-severe ulcerative colitis (UC) have expanded. However, comparative studies between these agents are limited, especially among biologic-naïve patients. We aimed to compare the persistence, effectiveness and safety of tofacitinib and vedolizumab as the first advanced treatment for patients with UC.

Long-term outcomes and predictors of vedolizumab persistence in ulcerative colitis.

Background: Long-term vedolizumab (VDZ) outcomes in real-world cohorts have been largely limited to 1-year follow-up, with few bio-naïve patients or objective markers of inflammation assessed.

Objectives: We aimed to assess factors affecting VDZ persistence including clinical, biochemical and faecal biomarker remission at 1, 3 and 5 years.

Design: We performed a retrospective, observational, cohort study.

Real-World Cohort Study on the Effectiveness and Safety of Filgotinib Use in Ulcerative Colitis.

Background: Filgotinib is a small molecule with preferential inhibition of Janus kinase type 1, approved for the treatment of ulcerative colitis in Scotland in May 2022. We present the first real world experience on its use in clinical practice.

Methods: In this retrospective, observational, cohort study we assessed patients with active ulcerative colitis who received filgotinib in NHS Lothian, Scotland.

Macrophages in intestinal homeostasis and inflammatory bowel disease.

Macrophages are essential for the maintenance of intestinal homeostasis, yet appear to be drivers of inflammation in the context of inflammatory bowel disease (IBD). How these peacekeepers become powerful aggressors in IBD is still unclear, but technological advances have revolutionized our understanding of many facets of their biology. In this Review, we discuss the progress made in understanding the heterogeneity of intestinal macrophages, the functions they perform in gut health and how the environment and origin can control the differentiation and longevity of these cells.

Longitudinal Fecal Calprotectin Profiles Characterize Disease Course Heterogeneity in Crohn's Disease.

Background And Aims: The progressive nature of Crohn's disease is highly variable and hard to predict. In addition, symptoms correlate poorly with mucosal inflammation. There is therefore an urgent need to better characterize the heterogeneity of disease trajectories in Crohn's disease by utilizing objective markers of inflammation.

Multiple infliximab biosimilar switches appear to be safe and effective in a real-world inflammatory bowel disease cohort.

Background: Switching from originator infliximab (IFX) to biosimilar IFX is effective and safe. However, data on multiple switching are scarce. The Edinburgh inflammatory bowel disease (IBD) unit has undertaken three switch programmes: (1) Remicade to CT-P13 (2016), (2) CT-P13 to SB2 (2020), and (3) SB2 to CT-P13 (2021).

Rates, predictive factors and effectiveness of ustekinumab intensification to 4- or 6-weekly intervals in Crohn's disease.

Background: The UNITI trial reports efficacy of ustekinumab (UST) dose intensification in Crohn's disease (CD) from 12- to 8-weekly, but not 4-weekly. We aimed 1) to assess the cumulative incidence of UST dose intensification to 4- or 6-weekly, 2) to identify factors associated with dose intensification, and 3) to assess the effectiveness of this strategy.

Methods: We performed a retrospective, observational cohort study in NHS Lothian including all UST treated CD patients (2015-2020).

Patterns of emergency admission for IBD patients over the last 10 years in Lothian, Scotland: a retrospective prevalent cohort analysis.

Objective: It is unclear how the compounding prevalence of inflammatory bowel disease (IBD) has translated into the causes and rates of hospitalisation, particularly in an era of increased biologic prescribing. We aimed to analyse these trends in a population-based IBD cohort over the last 10 years.

Design: The Lothian IBD registry is a complete, validated, prevalent database of IBD patients in NHS Lothian, Scotland.

Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab.

Anti tumour necrosis factor (anti-TNF) drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal and influenza vaccination. Here we report SARS-CoV-2 vaccine-induced immune responses and breakthrough infections in patients with inflammatory bowel disease, who are treated either with the anti-TNF antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.

Real-world experience with tofacitinib in ulcerative colitis: a systematic review and meta-analysis.

Background And Aims: Tofacitinib is a Janus kinase inhibitor (JAKi) recently approved for the treatment of moderate to severe ulcerative colitis (UC) based on robust efficacy and safety data derived from OCTAVE clinical trials. Evidence on the outcomes of tofacitinib therapy in real-world UC patients is needed, as a number of these patients would be deemed ineligible for clinical trials. We have therefore summarised data derived from observational, real-world evidence (RWE) studies on the effectiveness and safety of tofacitinib in moderate to severe UC patients.

The transcription factor EGR2 is indispensable for tissue-specific imprinting of alveolar macrophages in health and tissue repair.

Alveolar macrophages are the most abundant macrophages in the healthy lung where they play key roles in homeostasis and immune surveillance against airborne pathogens. Tissue-specific differentiation and survival of alveolar macrophages rely on niche-derived factors, such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor–β (TGF-β). However, the nature of the downstream molecular pathways that regulate the identity and function of alveolar macrophages and their response to injury remain poorly understood.

Infant dietary exposure to dioxin-like polychlorinated biphenyls (dlPCBs), polybrominated and mixed halogenated dibenzo-p-dioxins and furans (PBDD/Fs and PXDD/Fs) in milk samples of lactating mothers in Accra, Ghana.

In this study, polybrominated and mixed halogenated dibenzo-p-dioxins and furans (PBDD/Fs and PXDD/Fs), and dioxin-like polychlorinated biphenyls (dlPCBs) were quantified in 24 human milk samples of first-time lactating mothers from Greater Accra region in Ghana. The aims of the study were to determine the concentrations and toxic equivalent concentrations of PBDD/F, PXDD/F and dlPCBs in human milk, and to estimate an infant's daily intake. The samples were analysed for 12 dioxin-like PCBs, 7 congeners of 2,3,7,8-polybrominated dibenzo-p-dioxins and furans (PBDD/Fs), and 7 congeners of 2,3,7,8-mixed halogenated dioxins and furans (PXDD/Fs, where X = Br/Cl).

Normalization of Fecal Calprotectin Within 12 Months of Diagnosis Is Associated With Reduced Risk of Disease Progression in Patients With Crohn's Disease.

Background & Aims: The level of fecal calprotectin (FC) correlates with endoscopic evidence of inflammation in Crohn's disease (CD). A treat-to-target algorithm for patients with CD, that incorporates FC, outperforms a treatment strategy based on symptoms alone in the induction of mucosal healing at 12 months. We investigated whether normalization of FC within 12 months of diagnosis of CD is associated with a reduction in disease progression.

Paediatric Patients (Less Than Age of 17 Years) Account for Less Than 1.5% of All Prevalent Inflammatory Bowel Disease Cases.

The prevalence of inflammatory bowel disease (IBD) continues to rise globally; however, the true proportion of paediatric IBD patients remains unknown. We conducted an all-age, multiparameter, population-based search using capture-recapture methodology to identify all IBD cases to August 31, 2018 within Lothian, a defined health board and the largest of the 3 within South-East Scotland. Individual case note validation was performed for all 24,601 possible IBD cases according to internationally recognised diagnostic and age criteria.

The ACE (Albumin, CRP and Endoscopy) Index in Acute Colitis: A Simple Clinical Index on Admission that Predicts Outcome in Patients With Acute Ulcerative Colitis.

Background: Intravenous (IV) steroids remain the first-line treatment for patients with acute ulcerative colitis (UC). However, 30% of patients do not respond to steroids, requiring second-line therapy and/or surgery. There are no existing indices that allow physicians to predict steroid nonresponse at admission.

British Society of Gastroenterology guidance for management of inflammatory bowel disease during the COVID-19 pandemic.

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.

The Methyl-CpG-Binding Protein Mbd2 Regulates Susceptibility to Experimental Colitis via Control of CD11c Cells and Colonic Epithelium.

Methyl-CpG-binding domain-2 (Mbd2) acts as an epigenetic regulator of gene expression, by linking DNA methylation to repressive chromatin structure. Although Mbd2 is widely expressed in gastrointestinal immune cells and is implicated in regulating intestinal cancer, anti-helminth responses and colonic inflammation, the Mbd2-expressing cell types that control these responses are incompletely defined. Indeed, epigenetic control of gene expression in cells that regulate intestinal immunity is generally poorly understood, even though such mechanisms may explain the inability of standard genetic approaches to pinpoint the causes of conditions like inflammatory bowel disease.

IBD prevalence in Lothian, Scotland, derived by capture-recapture methodology.

Objective: IBD prevalence is estimated to be rising, but no detailed, recent UK data are available. The last reported prevalence estimate in the UK was 0.40% in 2003.

Background levels of dioxin-like polychlorinated biphenyls (dlPCBs), polychlorinated, polybrominated and mixed halogenated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs, PBDD/Fs & PXDD/Fs) in sera of pregnant women in Accra, Ghana.

Human exposure data on dioxins and dioxin-like compounds (DLCs) in Ghana are limited. Based on health risks associated with dioxins and DLCs, the impact of maternal body burdens on foetal exposure is significant. This is the first study that assesses polychlorinated, polybrominated and mixed halogenated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs, PBDD/Fs and PXDD/Fs), and dioxin-like polychlorinated biphenyls (dlPCBs) in sera of primiparous Ghanaians.