ABSTRACT Background Inflammatory bowel diseases (IBD) are a group of chronic inflammatory conditions affecting the gastrointestinal tract, which requires life‐long management. Healthcare inequalities in IBD are a key factor influencing disease outcomes. Aim This review aimed to describe the impact of geographical location (urban vs. rural) and socioeconomic status (SES) on IBD healthcare utilisation and clinical outcomes. Methods A systematic review was conducted analysing quantitative studies from developed countries from 3 databases (PubMed, EMBASE and Cochrane library), published between January 1st 2000 and January 1st 2024. Healthcare utilisation outcomes were summarised by surgical rates, medication utilisation, outpatient gastroenterology care, emergency room visits and hospitalisation rates. Clinical outcomes were summarised by mortality rates, IBD‐related complication and patient reported disease activity. Results Twenty‐nine studies met the inclusion criteria for this review. Patients from rural areas had reduced access to specialist IBD care and more frequent emergency room presentations, yet similar rates of hospital admissions, medication use, and clinical outcomes compared to urban patients. Socioeconomic status influenced both surgical and hospitalisation outcomes. Patients with lower SES had higher rates of IBD‐related hospitalisations and increased inpatient mortality. They were also less likely to undergo colectomy for ulcerative colitis or resective surgery for Crohn's disease. Discussion This study, which is focussed on developed countries, highlights how geographical location and socioeconomic factors affect IBD healthcare use and outcomes. As IBD prevalence rises and disease complexity grows, delivering cost‐effective, equitable and high‐quality care to all patients is becoming an increasing challenge for healthcare systems worldwide.

IntroductionUlcerative colitis (UC) is driven by mucosal inflammation and epithelial injury. Single cell RNA sequencing (scRNA-seq) enables high resolution profiling of immune, stromal and epithelial compartments in UC, whilst spatial transcriptomic (ST) and proteomic (SP) enable interrogation of cell-cell interactions, niche-specific expression profiles, and spatially restricted pathological processes. Although scRNA-seq, ST, and SP technologies have been rapidly evolved in the past ten years, relatively limited clinical applications have been demonstrated. This systematic review aims at comprehensively analysing current evidence in UC studies as an approach to identifying key limitations and proposing recommendations for strengthening future spatial research towards translations into clinics.MethodsA comprehensive search of Embase, Medline, and grey literature was conducted to identify studies using scRNA-seq or spatial transcriptomic or proteomic technologies in adult UC cohorts. Outcomes of interest included insights into disease pathogenesis or treatment response.ResultsscRNA-seq studies revealed alterations across the innate and adaptive immune systems, as well as stromal and epithelial compartments in UC colonic tissue. Spatial studies provided insights into: (i) cellular composition of the UC microenvironment; (ii) inflammatory features in treatment responders versus non-responders; and (iii) ligand-receptor interactions as potential spatial biomarkers and therapeutic targets.ConclusionOverall, single-cell and spatial studies are deepening our understanding of UC pathogenesis and treatment response. However, they are often limited by small sample sizes and heterogeneous UC phenotypes. Future studies should prioritise robust cohort design and careful sample stratification. This will be critical to generating mechanistically precise, reproducible, and clinically meaningful insights into the heterogeneity of UC pathogenesis and treatment response.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024601628.

Abstract Background Perianal disease is an increasingly recognised complication of ulcerative colitis (UC) (1). Variant rs4151651 in complement factor B (CFB) is associated with severe phenotype UC and, more recently, implicated in the pathogenesis of perianal Crohn’s disease (CD) (2, 3). In our previous work, we have shown the minor allele frequency (MAF) for the rs4151651 variant to be 0.03 for non-IBD affected control patients, 0.05 in patients with mild UC, and 0.13 in patients with severe phenotype UC (3). Here, we aim to determine the MAF for the rs4151651 variant in UC patients with perianal disease. Methods Ulcerative colitis patients with perianal disease were identified from our extensive inflammatory bowel disease (IBD) biobank. Perianal disease was defined as perianal abscesses or fistulae (haemorrhoids and anal fissures were excluded). Appropriate consent was obtained from all participants (HREC/14/QRBW/323). Demographic and phenotypic data were collected, and UC diagnoses were confirmed by expert IBD pathologists through histological review. To further confirm accurate phenotyping of our UC cohort, and to distinguish it from CD, we also present MAF data from the NOD2 gene, where available. Genotyping was either previously performed by genome-wide association study (GWAS) analysis or performed using the rs4151651 single nucleotide polymorphism (SNP). Results Forty-one patients were identified. Baseline demographics and clinical characteristics are presented in Table 1. Phenotypically and histologically all patients had disease consistent with UC. The MAFs for the NOD2 variants rs2066844, rs2066845 and rs2066847 were 0.04, 0.01 and 0.01 respectively. Eight patients had both a perianal abscess and a fistula, 1 patient had a perianal abscess only, and 33 patients had perianal fistulae only. Twenty-four patients in our cohort had a prior colectomy. The MAF for the rs4151651 variant in the 41 UC patients with perianal disease was 0.28. In the 21 patients who had extensive disease (E3), the MAF was 0.29. In the 24 patients who had a prior colectomy, the MAF was 0.30 (Figure 1). Conclusion The rs4151651 variant on the CFB gene is associated with perianal disease in UC patients. These findings align with prior studies linking the rs4151651 variant to a more severe UC phenotype. This SNP could be a valuable biomarker in predicting perianal complications for patients with severe UC undergoing colectomy and considering reconstructive (pouch) surgery. References 1.Choi YS, Kim DS, Lee DH, Lee JB, Lee EJ, Lee SD, et al. Clinical Characteristics and Incidence of Perianal Diseases in Patients With Ulcerative Colitis. Ann Coloproctol. 2018;34(3):138-43. 2.Akhlaghpour M, Haritunians T, More SK, Thomas LS, Stamps DT, Dube S, et al. Genetic coding variant in complement factor B (CFB) is associated with increased risk for perianal Crohn’s disease and leads to impaired CFB cleavage and phagocytosis. Gut. 2023;72(11):2068-80. 3.Mortlock S, Lord A, Montgomery G, Zakrzewski M, Simms LA, Krishnaprasad K, et al. An Extremes of Phenotype Approach Confirms Significant Genetic Heterogeneity in Patients with Ulcerative Colitis. J Crohns Colitis. 2023;17(2):277-88.

Objective During the early COVID-19 pandemic, UK guidelines advocated faecal immunochemical tests (FIT) with a threshold of 10 µg/g to help secondary care clinicians triage urgent suspected colorectal cancer (CRC) referrals. We aimed to evaluate the real-world performance and impact of FIT in a high-risk cohort referred against National Institute for Health and Clinical Excellence NG12 (2015) criteria.Methods Multicentre prospective observational cohort study of FIT at all four secondary care hospitals in Devon (UK) between 1 April 2020 and 31 December 2020. FIT use was at the discretion of primary and secondary care clinicians. Incident CRC cases were identified ≥12 months after general practitioner (GP) referral using regional National Bowel Cancer Audit data linkage. We assessed diagnostic accuracy and healthcare utilisation in patients with and without FIT.Results Overall, 6698 patients were included: 55% female, median age 72 years (IQR 65–82). Just over half (53%, 3552) of patients underwent FIT with a positivity rate of 34% (n=1237). CRC prevalence in patients with no FIT, positive FIT and negative FIT was 6% (189), 11% (137) and 0.5% (11), respectively. The prevalence of all cancers, including non-CRCs, was similar among FIT and no-FIT cohorts (p=0.74). Sensitivity and specificity of FIT for CRC were 0.93 (95% CI 0.87 to 0.96) and 0.68 (95% CI 0.66 to 0.69), respectively. Patients with negative FIT underwent fewer lower gastrointestinal endoscopies (no FIT 62% (1964) vs positive FIT 69% (857) vs negative FIT 36% (835)), p=0.0005).Conclusions FIT is a useful triage tool for patients with suspected CRC which safely reduces endoscopy demand and prioritises those at greatest cancer risk. Standardised regional referral pathways, greater use of ‘straight-to-test’ investigations and GP support are needed to maximise its impact.

Acute severe ulcerative colitis (ASUC) is a life-threatening medical emergency affecting over 20% of patients with ulcerative colitis (UC). Up to 40% of patients are refractory to intravenous corticosteroids (IVCS) and require rescue medical therapy or immediate colectomy. The potent Janus kinase (JAK) inhibitors, upadacitinib and tofacitinib, have proven efficacy in a randomised control trial setting for moderate-to-severe UC, but not ASUC. We describe a case series of sequential rescue therapy with JAK inhibitors following the failure of dose-intensified infliximab in corticosteroid-refractory ASUC. Six adult (>16 years old) patients received sequential rescue therapy with a JAK inhibitor (upadacitinib n = 5, tofacitinib n = 1) following failure of IVCS and dose-intensified infliximab at the Royal Brisbane and Women’s Hospital (QLD, Australia) between October 2023 and April 2024. All patients met the Truelove and Witts criteria for ASUC on admission. Data were captured during admission and at 90-days post-discharge. Co-primary outcomes were 90-day colectomy-free survival and inpatient clinical response (<4 non-bloody stools per day) 72 h after JAK-inhibitor initiation. Secondary outcomes included 90-day clinical (PRO-2 score < 1) and biochemical (faecal calprotectin (FCP) < 150 µg/g and C-reactive protein (CRP) < 5 mg/L) corticosteroid-free remission and adverse events. Median CRP on admission was 100 mg/L (interquartile range (IQR) 58–105), median FCP 3400 µg/g (IQR 910–4950) and median Mayo Endoscopic Score 3. Four out of six patients had a clinical response within 72 h of sequential JAK-inhibitor rescue therapy. Two patients underwent emergent inpatient colectomy for refractory disease – one of whom developed post-operative sepsis. Among the four JAK-responders at 90 days, all achieved corticosteroid-free clinical remission and three achieved biochemical remission. No other adverse events were recorded. There is a promising role for JAK inhibitors as sequential rescue therapy following the failure of dose-intensified infliximab in select patients with corticosteroid-refractory ASUC.

Abstract Background Inflammatory bowel disease (IBD) is a global health issue with Australia having amongst the highest prevalence rates worldwide. Our study examined the quality, safety and equity of care amongst ten Australasian centres using Crohn’s Colitis Care electronic management record. The aim was to describe current care delivery at each centre for a range of performance indicators to provide a baseline from which to engage in a regional care quality benchmarking initiative Methods Deidentified data prospectively entered by clinicians during routine clinical practice throughout 2022 were retrospectively analysed. Only centres with >100 eligible people with IBD and an assessment during the trial period were included. Sites from Australia and New Zealand were a mixture of public and private IBD referral centres Results The cohort included 7172 people with IBD from 10 centres; 58.6% with Crohn’s disease (CD), 39.1% ulcerative colitis (UC) and 2.3% IBD-unclassified (IBDU). Mean age was 44.3 (SD +/- 18.0) with an even gender balance (50.7% female). The number of people with IBD per centre ranged from 201 to 2151 (median 566). In the total cohort, 38.3% were currently on advanced IBD therapy (biologics or new small molecules), with centre variation from 30.8% to 43.5% (p<0.001). Of those on advanced therapy, 42% were on dose escalated therapy which varied between centres substantially from 18% to 64%. Current steroid use ranged from 0.3% to 6.1% (median 1.6%; p<0.001). Documented IBD surgical rates varied from 0.1% to 7.2% (median 2.0; p<0.001). IBD admission rates ranged from 0.1% to 13.6% (median 1.2; p<0.001) while current smokers comprised 1.7% to 12.5% (p<0.001) of the cohort with a mean of 6.0% across all ten centres. A total of 3,379 faecal calprotectin’s (FCP) with an overall remission rate (< 250μg/g) of 71% varying from 63.4% to 83.1% (median 69.1; p=0.001); 2,616 lower endoscopies were performed with an observed remission rate of 56%; this varied between sites from 0% to 69%. Recorded Influenza vaccination rates varied from 6.3% to 54.4% (median 19.8) and Covid vaccination rates from 14% to 78.5% (median 43.4). Skin care check completion rates ranged from 16.3% to 32.3% (median 22.9). The centre with the highest documented healthcare maintenance completion rate across all three domains was private. Conclusion Despite advances in treatment and much literature addressing care guidelines and targets, significant disparity in care documentation and outcomes remains for people with IBD in routine care. CCCare as an IBD-specific EMR supports easy, serial examination of these measures at scale and is therefore a useful tool to measure and drive efforts to improve these deficiencies and reduce unwarranted care variation

Abstract Background The impact of Inflammatory Bowel Disease (IBD) on individuals’ quality of life is well reported. Recent studies have shown that depression or anxiety affect almost 1 in 5 people with IBD and may be a predictor of active disease. We aimed to explore the burden of MHI in the Australasian IBD population and examine the real-world variation in screening and care across different sites and care settings Methods Crohn’s Colitis Care’s (CCCare) clinical quality registry (CQR) is created by deidentified data flowing across from routine care encounters. Data in the CQR for all individuals with a clinical encounter since August 2018 were interrogated in April 2023. Mental health data were collected from documentation during routine care or through patient consumer completion of embedded questionnaires, namely Depression Anxiety and Stress Scale 21 [DASS-21] and Kessler Psychological Distress Scale [K10] Results The CQR contained 6614 people with IBD with a mean age of 44.4 (SD +/- 22.09) and even gender distribution (50.9% female). 79.5% of people were from Australia and 20.5% from New Zealand. 57.1% of people had Crohn’s disease (CD), 40.4% ulcerative colitis (UC) and 2.5% IBDU with a mean disease duration of 13.3 years (SD +/-23.0). Anxiety was the 4th most listed comorbidity affecting 17.8% of individuals, depression 7th affecting 13.7% of people and both depression and anxiety 13th affecting 9.1% of people with IBD. In total 40.8% or 2 in 5 people with IBD in Australasia had received a formal diagnosis of a MHI. 2,928 consumers had been invited to complete the DASS-21 and 2,340 the K10 (44% & 35% respectively). Of the questionnaires sent, 32% of DASS-21s and 33% of K10s were completed. Rates of both invitation and completion varied significantly between centres. Invitation rates varied from 11% - 90% (p<0.001) while questionnaire completion rates varied from 26% to 46.8% (p<0.001). The mean DASS-21 score for all people with IBD was 8.1 for depression (7-10 indicating moderate disease), 6.6 for anxiety (6-7 suggests moderate disease) and 11.2 for stress (10-12 indicates moderate disease). Individuals with current fistulising CD (representing severe IBD phenotype) mean DASS-21 scores were higher than the wider IBD population, averaging 9.9 for depression (p<0.001), 7.4 for anxiety (p<0.001) & 12.9 for stress (p<0.001) Conclusion Individuals with IBD suffer from high rates of MHIs, with those suffering more severe disease phenotypes scoring worse on mental health assessment tools. Despite the availability of screening and monitoring tools, healthcare providers use these variably and insufficiently. This may result in unmet care needs. Standardisation of care addressing the psychosocial care needs of people with IBD is needed

Introduction A substantial proportion of patients with inflammatory bowel disease (IBD) on intravenous infliximab require dose intensification. Accessing additional intravenous infliximab is labour-intensive and expensive, depending on insurance and pharmaceutical reimbursement. Observational data suggest that subcutaneous infliximab may offer a convenient and safe alternative to maintain disease remission in patients requiring dose-intensified infliximab. A prospective, controlled trial is required to confirm that subcutaneous infliximab is as effective as dose-intensified intravenous infliximab, to identify predictors of disease flare and to establish the role of subcutaneous infliximab therapeutic drug monitoring.Methods and analysis The DISCUS-IBD trial is an investigator-initiated, prospective, multicentre, randomised, open-label non-inferiority study comparing the rate of disease flares in participants randomised to continue dose-intensified intravenous infliximab to those switched to subcutaneous infliximab after 48 weeks. Participants are adult patients with IBD in sustained corticosteroid-free remission on any regimen of dose-intensified infliximab up to a maximum of 10 mg/kg 4-weekly intravenously. Participants allocated to intravenous infliximab will continue infliximab at the same dose-intensified regimen they were receiving at study enrolment. Subcutaneous infliximab dosing will be stratified by prior intravenous infliximab dosing. Clinical (Harvey-Bradshaw Index, partial Mayo score), biochemical (C reactive protein, faecal calprotectin), pharmacokinetic (drug-level±antidrug antibodies) and qualitative data are collected 12-weekly until study conclusion at week 48. 13 sites across Australia will participate in recruitment to reach a calculated sample size of 120 participants.Ethics and dissemination Multisite ethics approval was obtained from the Health District Human Research Ethics Committee (HREC) at The Alfred Hospital under a National Mutual Acceptance (NMA) agreement (HREC/90559/Alfred-2022; Local Reference: Project 618/22, version 1.6, 2 March 2023). Findings will be reported at national and international gastroenterology meetings and published in peer-reviewed journals. DISCUS-IBD was prospectively registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR) prior to commencing recruitment.Trial registration number ACTRN12622001458729.