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 (interquartile range [IQR] 23-49). Among the cohort, 67% [61/91] were biologic- and small molecule-naïve, and 20.9% [19/91] had failed one and 12.1% [11/91] two or more 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 [C reactive protein ≤5 mg/L] was achieved in 87.3% [62/71] at Week 12 and 88.9% [40/45] at Week 24. Faecal biomarker [calprotectin <250 µg/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.

When modeling competing risks (CR) survival data, several techniques have been proposed in both the statistical and machine learning literature. State‐of‐the‐art methods have extended classical approaches with more flexible assumptions that can improve predictive performance, allow high‐dimensional data and missing values, among others. Despite this, modern approaches have not been widely employed in applied settings. This article aims to aid the uptake of such methods by providing a condensed compendium of CR survival methods with a unified notation and interpretation across approaches. We highlight available software and, when possible, demonstrate their usage via reproducible R vignettes. Moreover, we discuss two major concerns that can affect benchmark studies in this context: the choice of performance metrics and reproducibility.

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. We aimed to better understand this heterogeneity by clustering Crohn's disease patients with similar longitudinal fecal calprotectin profiles. We performed a retrospective cohort study at the Edinburgh IBD Unit, a tertiary referral center, and used latent class mixed models to cluster Crohn's disease subjects using fecal calprotectin observed within 5 years of diagnosis. Information criteria, alluvial plots, and cluster trajectories were used to decide the optimal number of clusters. Chi-square test, Fisher's exact test, and analysis of variance were used to test for associations with variables commonly assessed at diagnosis. Our study cohort comprised 356 patients with newly diagnosed Crohn's disease and 2856 fecal calprotectin measurements taken within 5 years of diagnosis (median 7 per subject). Four distinct clusters were identified by characteristic calprotectin profiles: a cluster with consistently high fecal calprotectin and 3 clusters characterized by different downward longitudinal trends. Cluster membership was significantly associated with smoking (P = .015), upper gastrointestinal involvement (P < .001), and early biologic therapy (P < .001). Our analysis demonstrates a novel approach to characterizing the heterogeneity of Crohn's disease by using fecal calprotectin. The group profiles do not simply reflect different treatment regimens and do not mirror classical disease progression endpoints.

Summary: 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. ICD‐10 coding of hospital discharge letters from all IBD patient admissions to secondary care between 1 January 2010 and 31 December 2019 was interrogated for admission cause, with linkage to local/national data sets on death and prescribed drugs.Results: Fifty‐seven per cent (4673/8211) of all IBD patients were admitted to secondary care for >24 h between 1 January 2010 and 31 December 2019. In patients 60 years (19% of admissions). Three per cent (243/8211) of IBD patients accounted for 50% of the total IBD bed‐days over the study period.Age‐standardised IBD admission rates fell from 39.4 to 25.5 admissions per 100,000 population between 2010 and 2019, an average annual percentage reduction of 3% (95% CI −4.5% to −2.1%, p < 0.0001). Non‐IBD admission rates were unchanged overall (145–137 per 100,000 population) and specifically for serious (hospitalisation) and severe (ITU admission or death) infection over the same period.Conclusion: Despite compounding prevalence and increased biologic use, IBD admission rates are falling. The cause of admission varies with age, with infection the predominant cause in older patients.

Background IBD is characterised by recurrent flares, but evidence on whether modifiable dietary factors influence flare risk is limited. Objective The PREdiCCt study was designed to examine demographic, clinical and dietary factors associated with disease flare among patients with IBD in self-reported remission. Design Multicentre, prospective cohort study conducted across 47 UK centres. Patients with Crohn’s disease (CD), ulcerative colitis (UC) or IBD unclassified (IBDU) in self-reported remission were prospectively followed up. The baseline diet was assessed using a validated food frequency questionnaire. The primary outcome was time to patient-reported flare (captured by monthly IBD-Control) and objective flare (clinical flare plus C-reactive protein >5 mg/L and/or faecal calprotectin (FC) >250 µg/g with treatment escalation). Associations were evaluated using Cox frailty models adjusted for demographic, clinical and biochemical variables, including baseline FC. Results Between November 2016 and March 2020, 2629 participants (1370 CD; 1259 UC/IBDU) were enrolled and followed up for a median of 4.1 years (IQR 3.0–5.0). Baseline FC was strongly associated with patient-reported flares (FC ≥250 µg/g: adjusted HR (aHR) 2.22; FC 50–250 µg/g: aHR 1.52 (reference <50 µg/g)) and objective flares (FC ≥250 µg/g: aHR 3.25; FC 50–250 µg/g: aHR 1.98). In UC, higher total meat intake was associated with increased risk of objective flares (highest versus lowest quartile: aHR 1.95, 95% CI 1.07 to 3.56). No consistent associations were observed for ultraprocessed foods, fibre or polyunsaturated fatty acids and flare. Conclusion Higher habitual meat intake was associated with increased risk of objective flare in UC, suggesting diet may contribute to flare susceptibility in specific patient groups. Trial registration number NCT03282903.

Background: The impact of advanced therapy prescribing on colectomy rates in ulcerative colitis (UC) is unknown with conflicting published evidence.Aim: To describe advanced therapy prescribing trends and colectomy rates for patients with UC in Lothian, UK between January 1st, 2004 and December 31st, 2023.Methods: We obtained incidence and prevalence data from the Lothian IBD Registry, a rigorously validated population cohort. We report advanced therapy prescribing and colectomy data as raw numbers and annual incidence rates. We used piecewise linear regression analyses to identify temporal trends in prescription and colectomy rates.Results: The prevalence of UC increased from 216 to 441 per 100,000 population in the 20 years from 2004, culminating in a total of 4115 patients with UC in 2023. We identified 720 patients who had received an advanced therapy. Prescribing of first‐line advanced therapy increased from 0 in 2004 to 115 in 2023, equating to 0.00 and 2.82 per 100 patients with UC. We identified 563 patients of the prevalent UC population who had colectomy, of whom 68% were performed as emergencies. Absolute colectomy numbers decreased from 42 in 2004 to 7 in 2023, equating to 2.48 and 0.22 per 100 patients with UC. A join point in 2013 was found for both increased advanced therapy prescribing and decreased colectomy rates.Conclusion: The incidence of colectomy in the UC population has decreased over time while the use of advanced therapies has greatly increased.