Real-world effectiveness of upadacitinib in Crohn's disease: a UK multicentre retrospective cohort study.

Background: Upadacitinib is a Janus kinase inhibitor, which has recently been approved for treating Crohn's disease. There are limited real-world studies on the outcomes of upadacitinib in Crohn's disease. Objective: Our aim was to evaluate the outcomes of upadacitinib in a real-world Crohn's disease cohort. Methods: We conducted a retrospective, multicentre, cohort study over a 2-year period across National Health Service (NHS) Lothian and Royal Devon University Healthcare NHS Foundation Trust. The primary outcome was treatment persistence at week 24. Secondary endpoints were corticosteroid-free clinical remission (Harvey-Bradshaw Index (HBI)<5) and biomarker remission (C-reactive protein (CRP)≤5 mg/L and faecal calprotectin (FCAL)<250 µg/g) at 12, 24 and 52 weeks. We recorded adverse events. Results: 135 patients commenced upadacitinib as of the 1 January 2024, of which 93 patients with active Crohn's disease were included with a minimum of 12 weeks follow-up. The median follow-up time was 25 weeks (IQR 15-42 weeks). 82% of the cohort had exposure to at least two classes of advanced therapies, and 52% had exposure to at least three classes of advanced therapies. Treatment persistence was 87.1% at week 12, 81.7% at week 24 and 62.8% at week 52. Rates of clinical remission were 64% (42/66), 48% (22/46) and 38% (8/21) at weeks 12, 24 and 52, respectively. Significant reductions in HBI, CRP and FCAL were observed during follow-up. 14% (13/91) had a hospitalisation due to Crohn's disease. Adverse events occurred in 40% (37/93) of the cohort, of which 12% (11/93) were serious. Conclusion: Upadacitinib was effective in a real-world, highly refractory, Crohn's disease cohort with good persistence.

Comprehensive review and update of stricturing Crohn's disease.

Up to 50% of patients with Crohn's disease develop a stricture within 10 years of diagnosis. Crohn's strictures can compose of inflammation, fibrosis or smooth muscle expansion and usually a combination of these. There have been numerous new developments in imaging modalities in determining the composition of Crohn's strictures. Magnetic resonance imaging remains the best upfront imaging modality to characterize Crohn's strictures. Gastrointestinal ultrasound (GIUS) has an increasing role in clinical practice, particularly for monitoring stricture response as a treat-to-target tool. Novel imaging techniques to differentiate between fibrosis and inflammatory strictures have been developed including contrast-enhanced GIUS, strain or shear wave elastography with GIUS and multiple new magnetic resonance imaging (MRI) protocols, including diffusion weighted, delayed contrast enhancement and magnetization transfer MR protocols. However, these techniques require further validation and standardization. Regarding therapeutics, anti-tumor necrosis agents with a treat-to-target strategy have the highest quality evidence in treating strictures and can lead to stricture regression in some cases. Endoscopic balloon dilatation remains a mainstay in the treatment algorithm of treating predominantly fibrostenotic Crohn's strictures, particularly those which are symptomatic, < 5 cm in length and not causing prestenotic dilatation. Endoscopic balloon dilatation has greater effectiveness in anastomotic strictures. Surgery remains an important treatment option in Crohn's strictures, with segmental resection and stricturoplasty having their own advantages and disadvantages. Kono-S anastomosis may be superior to conventional anastomosis for endoscopic recurrence; however, further high-quality studies are required to confirm this. Using risk stratification models such as the BACARDI risk model is important to guide management decisions between a medical and surgical approach. Early post-operative medical prophylaxis with an advanced therapy is an important consideration to prevent disease recurrence. This review expands on the above topics, highlights research gaps and provides a suggested investigation and management pathway in stricturing Crohn's disease.

Identifying the real-world challenges of dysplasia surveillance in inflammatory bowel disease: a retrospective cohort study in a tertiary health network.

BACKGROUND: Dysplasia surveillance in inflammatory bowel disease (IBD) is often suboptimal and deviates from guidelines. AIMS: To assess dysplasia surveillance behaviours and adherence to guidelines amongst a large tertiary teaching health network with a specialised IBD unit to identify areas where dysplasia surveillance could be improved. METHODS: A retrospective audit of IBD surveillance colonoscopy practice over an 18-month period was performed using the Provation Endoscopy Database and the hospital's primary sclerosing cholangitis database. RESULTS: The audit identified 115 dysplasia surveillance colonoscopies. A total of 37% of index dysplasia colonoscopies were outside recommended guidelines. A total of 10% had inadequate bowel preparation and only 40% had excellent bowel preparation. A total of 28% of patients underwent dye-based chromoendoscopy and 69% underwent high-definition white-light endoscopy. Dye chromoendoscopy was more likely to be used by IBD specialists than interventional endoscopists (P = 0.008) and other endoscopists (P = 0.004). Only IBD specialists and interventional endoscopists used dye chromoendoscopy. Dysplasia or colorectal cancer was detected in 3.4% of the colonoscopies. Overall, the several dysplasia examinations were lower than expected. CONCLUSIONS: Dysplasia surveillance in the IBD population remains an area of improvement given the current national guidelines. IBD specialists are more likely to perform dye chromoendoscopy than other endoscopists/gastroenterologists. Dysplasia rates in this real-world contemporary setting are less than expected in historical studies and may represent improvements in IBD management principles and medications.

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. Baseline demographic, phenotype and follow-up data were collected via review of electronic medical records. RESULTS: We included 91 patients with median treatment duration of 39 weeks (IQR 23-49). Among the cohort, 67% (61/91) were biologic and small molecule naïve, whilst 20.9% (19/91) had failed one and 12.1% (11/91) ≥2 classes of advanced therapy. Of the biologic and small molecule naïve patients, 18% (11/61) were also thiopurine naïve. Clinical remission (partial Mayo score <2) was achieved in 71.9% (41/57) and 76.4% (42/55) of patients at weeks 12 and 24 respectively. Biochemical remission (CRP≤5mg/L) was achieved in 87.3% (62/71) at week 12 and 88.9% (40/45) at week 24. Faecal biomarker (calprotectin <250µg/g) remission was achieved in 82.8% (48/58) at week 12 and 79.5% (35/44) at week 24.At the end of follow-up, median 42 weeks (IQR 27-50), 82.4% (75/91) of patients remained on filgotinib. Severe adverse events leading to drug discontinuation occurred in 2.2% (2/91) and there were 8.8% (8/91) moderate adverse events that required temporary discontinuation. CONCLUSION: These are the first reported data on the real-world efficacy and safety of filgotinib in ulcerative colitis. Our findings demonstrate that filgotinib is an effective and low risk treatment option for these patients.

IBD barriers across the continents: a continent-specific analysis - Australasia.

Australasia, encompassing Australia, New Zealand, and Papua New Guinea, has some of the highest prevalence's of inflammatory bowel disease (IBD) in the world. The way IBD medicine is practiced varies between and within these countries. There are numerous shared issues of IBD care between Australia and New Zealand, whereas Papua New Guinea has its' own unique set of circumstances. This review looks to explore some of the barriers to IBD care across the continent from the perspective of local IBD healthcare professionals. Barriers to IBD care that are explored include access to IBD multidisciplinary teams, provision of nutritional-based therapies, the prevalence and engagement of IBD-associated mental health disorders, access to medicine, access to endoscopy, rural barriers to care, Indigenous IBD care and paediatric issues. We look to highlight areas where improvements to IBD care across Australasia could be made as well as address research needs.

A home-based, multidisciplinary liver optimisation programme for the first 28 days after an admission for acute-on-chronic liver failure (LivR well): a study protocol for a randomised controlled trial.

BACKGROUND: Acute-on-chronic liver failure (ACLF) represents a rising global healthcare burden, characterised by increasing prevalence among patients with decompensated cirrhosis who have a 28-day transplantation-free mortality of 33.9%. Due to disease complexity and a high prevalence of socio-economic disadvantage, there are deficits in quality of care and adherence to guideline-based treatment in this cohort. Compared to other chronic conditions such as heart failure, those with liver disease have reduced access to integrated ambulatory care services. The LivR Well programme is a multidisciplinary intervention aimed at improving 28-day mortality and reducing 30-day readmission through a home-based, liver optimisation programme implemented in the first 28 days after an admission with either ACLF or hepatic decompensation. Outcomes from our feasibility study suggest that the intervention is safe and acceptable to patients and carers. METHODS: We will recruit adult patients with chronic liver disease from the emergency departments, in-patient admissions, and an ambulatory liver clinic of a multi-site quaternary health service in Melbourne, Australia. A total of 120 patients meeting EF-Clif criteria will be recruited to the ACLF arm, and 320 patients to the hepatic decompensation arm. Participants in each cohort will be randomised to the intervention arm, a 28-day multidisciplinary programme or to standard ambulatory care in a 1:1 ratio. The intervention arm includes access to nursing, pharmacy, physiotherapy, dietetics, social work, and neuropsychiatry clinicians. For the ACLF cohort, the primary outcome is 28-day mortality. For the hepatic decompensation cohort, the primary outcome is 30-day re-admission. Secondary outcomes assess changes in liver disease severity and quality of life. An interim analysis will be performed at 50% recruitment to consider early cessation of the trial if the intervention is superior to the control, as suggested in our feasibility study. A cost-effectiveness analysis will be performed. Patients will be followed up for 12 weeks from randomisation. Three exploratory subgroup analyses will be conducted by (a) source of referral, (b) unplanned hospitalisation, and (c) concurrent COVID-19. The trial has been registered with the Australian New Zealand Clinical Trials Registry. DISCUSSION: This study implements a multidisciplinary intervention for ACLF patients with proven benefits in other chronic diseases with the addition of novel digital health tools to enable remote patient monitoring during the COVID-19 pandemic. Our feasibility study demonstrates safety and acceptability and suggests clinical improvement in a small sample size. An RCT is required to generate robust outcomes in this frail, high healthcare resource utilisation cohort with high readmission and mortality risk. Interventions such as LivR Well are urgently required but also need to be evaluated to ensure feasibility, replicability, and scalability across different healthcare systems. The implications of this trial include the generalisability of the programme for implementation across regional and urban centres. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12621001703897 . Registered on 13 December 2021. WHO Trial Registration Data Set. See Appendix 1.

Jaundice, hepatosplenomegaly, and portal lymphadenopathy in a middle-aged female: Is it lymphoma?

Primary biliary cholangitis is a rare liver disease which often progresses to cirrhosis. It can be difficult to diagnose as patients are often asymptomatic initially or merely complain of fatigue or pruritus. We describe the case of a 56-year-old female who presented with a 2-month history of painless jaundice and constitutional symptoms. Computed tomography scan showed massive hepatosplenomegaly with abdominal lymphadenopathy. Liver biopsy and a strongly positive antimitochondrial antibody titer confirmed the diagnosis of primary biliary cholangitis.