bluuebunny/crossref_metadata_2025_split huggingface dataset:
P854 Tofacitinib demonstrates preliminary efficacy in induction of remission in chronic pouchitis
Authors: Khoo E , Amiss A , Ding J N , Bryant R , Mohsen W , Connor S , Leung R , Croft A , Lynch K , Sparrow M , De Cruz P , An Y K , Holtmann G , Begun J 
Published: January 2024

Abstract

Background
Pouchitis is common following total proctocolectomy for ulcerative colitis (UC) and ileal pouch-anal anastomosis (IPAA) and generally responds to antibiotics. However, up to 20% of patients develop either antibiotic-dependent or antibiotic-refractory pouchitis, collectively referred to as chronic pouchitis.

Methods
We report our preliminary induction results from a multi-center open label induction with randomized withdrawal trial to assess the efficacy of tofacitinib in chronic pouchitis. All eligible participants received 10mg tofacitinib twice daily for 8 weeks, with an additional 8 weeks of therapy given to patients with an inadequate initial clinical response. The primary endpoint was clinical response (a reduction of clinical PDAI≥2) at week 8. Secondary endpoints included endoscopic response (a reduction of endoscopic PDAI≥2), mPDAI remission (modified pouchitis disease activity index (mPDAI)≤ 4 and a reduction of mPDAI≥2), mPDAI response (a reduction of mPDAI≥2) and improvement in health-related quality of life (HRQoL) using the short inflammatory bowel disease questionnaire (SIBDQ). Serum cytokine levels was analyzed using LEGENDplex human inflammation panel 1. Univariate analysis was performed to identify clinical and biochemical predictors of response to tofacitinib.

Results
A total of 33 patients with chronic pouchitis (Table 1) were included in the preliminary analysis. The clinical and endoscopic response rates at week 8 were 55% and 58% respectively, with a median improvement of 1 (p&lt;0.05) and 3 (p&lt;0.05) respectively (Figure 1). The mPDAI remission rate was 49% at week 8 with an mPDAI response rate of 73%. Endoscopic responders exhibited significant improvements in endoscopic oedema, granularity, friability, and mucous exudate (p&lt;0.05). There was significant improvement in HRQoL, with the median SIBDQ score increasing from 35 at baseline to 54 at week 8 (p&lt;0.05). Eleven patients received a further 8 weeks of therapy with a clinical response rate of 36%, yielding an overall response rate including extended induction of 67%. Univariate analysis did not reveal significant differences in baseline characteristics, clinical, or biochemical markers between responders and non-responders. However, a history of corticosteroid use (p=0.08) and high baseline levels of faecal calprotectin (p=0.15) demonstrated a non-significant association with treatment response. Elevated baseline serum levels of IL-1b, IFN-a and IL-33 were associated with a treatment response at week 8 (p&lt;0.05).

Conclusion
Tofacitinib demonstrated preliminary efficacy in inducing both clinical and endoscopic response in patients with chronic pouchitis who have undergone IPAA for UC.
P856 Influential factors on the clinical and radiological closure of resistant perianal fistula treated with stoma
Authors: Candan S , Bakkaloglu O K , Bayar M , Eskazan T , Hatemi I , Erzin Y , Celik A F 
Published: January 2024

Abstract

Background
Perianal fistula (PaF) is a debilitating and difficult to treat form of Crohn's disease. Although biological (anti-TNF) treatments are almost always used, long term fistula closure rates are far from being satisfactory. Radiological closure, which should be the treatment goal, is even much rarer. Stoma is one of the last steps in the treatment of resistant fistula. In our study, we examined the patients who underwent stoma, in our series, due to resistant PaF and the factors associated with radiological closure.

Methods
Crohn's disease cohort was retrospectively evaluated for patients with resistant perianal fistula (history of poor response to anti-TNF) who underwent stoma. Demographic, treatment, and clinical characteristics of the patients were evaluated in terms of radiological closure (complete resolution of the fistula tract, disappearance of T2 hyperintensity and absence of contrast enhancement on MRI) of the PaF.

Results
There were 47 patients (11%) who underwent stoma due to perianal fistula among 423 Crohn's disease patients with PaF. The median age in the patient group (at the time of stoma) was 34 years and 47% of the patients were male. Radiological fistula closure was achieved in 42% of the patients and clinical remission (&gt;3 months) was achieved in 66%. Table -1 summarizes the comparison of demographic, clinical and treatment parameters of the study group and patients with and without radiological closure. Radiologic closure and non-closure groups were similar regarding pre-stoma- and during stoma treatment status. Being a never smoker was associated with poor radiological closure and could be an indicator of treatment resistance while ex-smoker status had a favorable outcome. Both recurrent antibiotic treatment (&gt;2/year) need for clinical fistula closure and history of seton replacement were associated with radiological unresponsiveness. During stoma, the early partial radiological response - achieved in the 3rd month of perianal MRI fistulography -was strongly associated with later radiological closure in the follow up. In Kaplan-Meir analysis; anatomically branching fistula had the poorest response, but the number of fistula did not have any influence, mucosal remission was associated with earlier and better radiological response, pre-stoma reccurent antibiotic need was associated with worse outcome Figure 1.

Conclusion
Radiological closure of PaF can be achieved with stoma in nearly half of the patients under already combined conventional treatment. History of seton replacement, recurrent antibiotic need and being never smoker are the indicators of resistance to radiological closure. Third month radiological response – is an important and early sign of radiological complete fistula closure.
P885 Pharmacokinetics, pharmacodynamics, and immunogenicity of biosimilar infliximab in pediatric patients with inflammatory bowel disease
Authors: Dipasquale V , Alibrandi A , Pellegrino S , Ramistella V , Romano C 
Published: January 2024

Abstract

Background
The pharmacokinetics and pharmacodynamics of biosimilar infliximab (IFX-BioS) in pediatric inflammatory bowel disease (IBD) are poorly understood. We examined some factors predicting IFX-BioS trough levels (TLs) in children.

Methods
Children with Crohn's disease (CD) and ulcerative colitis (UC) with an indication to start IFX-BioS in our center were prospectively included (January 2021-June 2022). TLs were measured with an in vitro lateral flow immunoassay (therapeutic range:3-7 microg/mL) at the 4th and 6th infusions and correlated with several covariates.

Results
A total of 110 TLs in 55 children (34 UC and 21 CD) were included. The mean TLs were 8.8±7.6 microg/mL and 9.8±6.7 microg/mL at the 4th and 6th infusions, respectively. The multivariate linear regression model at the 4th infusion found a positive correlation between TLs and age at diagnosis (B: 1.950, 95% CI: [0.019, 3.882], p=0.048) and IFX-BioS dose/kg (B: 1.962, 95% CI: [0.238, 3.687], p=0.029), and a negative correlation with clinical scores (B: -0.401, 95% CI: [-0.738, -0.064], p=0.023). At the 6th infusion, female gender (B: 6.887, 95 CI: [0.861, 12.913], p=0.029), hemoglobin (B: 1.853, 95% CI: [0.501, 3.204], p=0.011), and IFX-BioS dose/kg (B: 1.792, 95% CI: [0.979, 2.605], p&lt;0.001) were found to be positively correlated to TLs. Clinical remission was achieved in 71% (4th infusion) and 67.2% (6th infusion) of patients. Logistic regression analysis revealed no significant association between combined clinical and biochemical remission and TLs at the 4th (OR: 0.010, 95% CI: [0.928; 11.099], p=0.819) or 6th (OR: 0.017, 95% CI: [0.924; 1.119], p=0.732) infusion, corrected for IFX-BioS dose/kg and interval between infusions.

Conclusion
We discovered some predictors IFX-BioS TLs in IBD children. Understanding the IFX-BioS pharmacokinetics and pharmacodynamics could allow physicians to identify which patients are at higher risk of poor outcomes and adjust treatment accordingly.
P889 Facilitating equitable IBD care trust-wide: a need for treatment targets in IBD?
Authors: Hentges M , Ibarra A , Onyl Ronquillo F , Gnanasampanthan S , O’Shea I , Utulu S , Vlachou F , Gordon H , Jawad N 
Published: January 2024

Abstract

Background
Timely biological therapy in IBD is associated with reduced disease progression, especially in CD (Berg et al 2019). However, there are no clear UK standards detailing the timescale in which IBD care should be delivered. We evaluated the time between initial consideration of therapy and first dose in a district general hospital and tertiary referral centre in Barts Health NHS Trust.

Methods
Details of patients receiving biologics for IBD at Newham (NUH) and Royal London Hospital (RLH) (between 2018 – 2022) were obtained from infusion clinics; electronic records were reviewed for 50 recent referrals. The following information was collected: demographics, phenotype, drug, first documentation of consideration of biologic, completion of funding application, onset of therapy.

Results
Demographics:
NUH: Age (median(IQR)) = 43.5(30.3 – 50.56) Gender (F:M) = 26:24, CD:UC = 34:16, Biologic: infliximab:vedolizumab:ustekinumab:adalimumab: 29:5:11:5, First biologic: n=34
RLH: Age (median(IQR)) = 31.6 (24.6 – 41.1) Gender (F:M) = 27:23 CD:UC = 23:27, Biologic: infliximab:vedolizumab:ustekinumab:adalimumab: 34:12:3:1, First biologic: n=25
There was substantially longer time between initial consideration of therapy and first dose delivered at NUH 94.5 days (44 – 174) compared with RLH 35.5 days (23.75 –69) (p&lt;0.01). However, time from completion of funding application to first dose did not differ significantly between sites (43.5 days (30.3 – 50.6) vs 31.6 (24.6 – 41.1), p=0.42). In patients receiving first biologic, there was a trend towards a longer time since diagnosis at NUH (3.2 years (1.0 – 9.1) vs 1.7 years (0.5 – 4.3), p=0.08).

Conclusion
Patients treated in a tertiary referral centre started biologics sooner after consideration, and earlier in disease course. This does not appear due to availability of infusion services, but due to time to complete initial investigations and finalise escalation. This may reflect differences in service set-up; in particular, NUH manages IBD care with a single IBD nurse, and fewer options for fast-track clinic follow up. A clear UK IBD standards framework identifying recommended time frames for establishing biologics is indicated, to ensure equity in care across tertiary and DGH settings.
P912 A Real-World Evidence Study of Dose Escalation and associated costs of advanced therapies for Ulcerative Colitis in France and United Kingdom
Authors: Treuer T , Richards M , Mert C , Dhesi E , Silva L , Tan Y , Hoque S 
Published: January 2024

Abstract

Background
Dose escalation to optimize advanced therapies is common practice in ulcerative colitis (UC) to avoid intra-class or inter-class drug switching and maintain clinical response. Dose escalation also has impact on healthcare resource utilization (HRU) and costs. However, there are limited data available on real-life dose-escalation. Study aim was to understand real-world dose escalation/de-escalation UC advanced therapy drugs patterns in two European countries (France, United Kingdom [UK]).

Methods
This retrospective study analysed data from the THIN®/CEGEDIM database to identify adult patients with moderate-to-severe UC who were naïve to advanced UC therapies or had not received any of the UC advanced therapy drugs of interest (adalimumab [ADA], golimumab [GOL], infliximab [INF], tofacitinib [TOF], ustekinumab [UST], or vedolizumab [VED]) for at least 12 months prior first prescription (and/or dispensation for France) between January 2017 and February 2022. A dose increase of ≥20% during the maintenance period compared to lowest Summary of Product Characteristics recommended dose was considered dose escalation. Proportions of patients with dose escalation after maintenance date were estimated using Kaplan-Meier (KM) survival analyses. Clinical response (defined as absence of: UC-related hospitalization or colectomy, treatment switch or addition of another UC advanced drug, systemic/rectal corticosteroids exposure), and direct (consultations, hospitalisations, diagnostic tests, UC drugs, complementary therapy) and indirect costs related to UC by treatment cohort were also analysed.

Results
1663 patients fulfilled the selection criteria, of whom 619 had information on dose patterns. Overall, 89% of patients (range 33% [INF] to 100% [GOL, TOF, and UST]) had dose escalation within the first 24 months after start of maintenance, with a median % dose increase ranging from +15% [VED] to +198% [GOL] (Table). Median (95% CI) time to first dose escalation was 2.1 (1.8-2.4) months (range 0.7 [UST] to 4.6 [VED]). Clinical response ranged from 56.3% (ADA) to 77.0% (INF). Direct annual HRU costs related to UC ranged from 3,085 (INF) to 16,527 (UST) EUR in France and from 1,857 (INF) to 4,104 (VED) GBP in the UK. Mean direct HRU costs in France were 25% higher in escalated patients compared to de-escalated patients (range: +4.2% GOL to +61.9% UST).

Conclusion
Dose escalation of advanced therapies for UC is a common strategy to avoid treatment-switching. Despite dose escalations and their cost to the system, a proportion of patients fail to achieve clinical response, highlighting the need for more efficacious and durable treatments for patients with moderate-to-severe UC.
P914 Immunogenecity of Hepatitis B Vaccination in Patients with Ulcerative Colitis on Infliximab Monotherapy : A Prospective Comparative Study
Authors: Shehab M , Alfadhli A 
Published: January 2024

Abstract

Background
Hepatitis B virus (HBV) infection has been associated with chronic hepatitis and cirrhosis. Patients with inflammatory bowel disease (IBD) maybe at higher risk of HBV infection, especially those on biologic therapies. There is limited data on the effectiveness of HBV vaccination in patients with IBD receiving different types of IBD medications. This study intends to compare the effectiveness of HBV vaccine in patients with ulcerative colitis (UC) on Infliximab (IFX) compared to those on 5-aminosalicylic acid (5-ASA).

Methods
Patients with UC aged between 18-85 years were prospectively enrolled in the study. The patients were divided into two groups: group 1 ( patients with UC on 5-ASA) and group 2 (patients with UC on IFX). HBV vaccination was administered (20 mcg) following the standard regimen, and Hepatitis B serum antibody (HbsAb) titres were assessed three months after the final dose. The response to HBV vaccines was categorized as 'adequate' immune response (≥10 IU/L) and 'effective' immune response (≥100 IU/L).

Results
In our final analysis of 118 patients with UC, 54.2% were male, and 52.5% had extensive disease. HBsAb titer levels were significantly higher in the 5ASA group (126.7 ± 37.5) compared to the IFX group (55.5 ± 29.4). Stratifying HBsAb levels into two categories (≥10-99 IU/L and ≥100 IU/L) revealed a significantly greater proportion of subjects in the 5-ASA group with levels ≥100 IU/L (76.7%) compared to the IFX group (12.1%). Conversely, the IFX group showed a higher percentage of subjects with levels between 10-99 IU/L (87.9%) relative to the 5-ASA group (23.3%). Logistic regression analysis demonstrated that patients with UC receiving 5-ASA were 23.94 times more likely to exhibit HBsAb levels ≥100 compared to those on IFX (OR 23.94, 95% CI 8.89-64.49).

Conclusion
Immune response to hepatitis B vaccination in patient with ulcerative colitis on infliximab is attenuated compared to those on 5-ASA. Therefore emphasizing the importance of HBV vaccination for patients with IBD before starting anti-TNF therapy, especially infliximab, and advocating for screening is imperative in high risk countries.
P925 Predicted inflammatory status and Inflammatory Bowel Disease among Korean adults: a Multicentre case-control study
Authors: Kim D H , Okekunle A P , Kang J , Kim H S , Kim S H , Jung M K , Park J H , Na S Y , Lee J E , Lim Y J , Chun H 
Published: January 2024

Abstract

Background
Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a complex disease attributable to an anomalous immune response to intestinal microbiome antigenic stimulation, but there are limited studies on the overall implication of diet and lifestyle factors in the development of IBD, particularly among East Asian. This study assessed the association of pro-inflammatory predicted high sensitivity C-reactive protein (hs-CRP) scores (derived from diet and lifestyle factors) with IBD among Korean adults.

Methods
From July 2017 to September 2023, 912 subjects who underwent gastrointestinal endoscopy at eight tertiary medical centres and completed a food frequency questionnaire were used in this study. The study included subjects with IBD and matched them in a 1:1 ratio (using propensity score matching) with normal control; subjects without colonic inflammation or cancer. Pro-inflammatory predicted hs-CRP score was derived from sociodemographic, lifestyle, and dietary information and multivariable-adjusted conditional logistic regression model was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of IBD by tertile distribution of predicted hs-CRP scores (adjusting for age, sex alcohol intake, smoking, education, physical activity and energy-adjusted dietary energy intakes) at a two-sided P&lt;0.05.

Results
Overall, 127 patients with IBD and 127 healthy controls were included in the study after propensity score matching. Of 127 IBD cases, 59 (46.5%) presented with CD and 51 (40.2%) were females. The prevalence of alcohol use was higher in the healthy control group compared to IBD patients (70.1% vs. 48.0%, p &lt; 0.05), while a BMI ≥ 23 was more common in IBD patients (58.3% vs. 35.4%, p &lt; 0.05). Smoking, age, sex, physical activity, and energy intake differed insignificantly between the two groups. Overall, the median (interquartile range) of the predicted hs-CRP was -2.6 (-3.0, -2.2), and multivariable-adjusted ORs and 95% CIs for IBD by tertiles of the predicted hs-CRP score were 1.00, 1.00 (0.44, 2.25), 8.67 (2.24, 33.51; P trend = 0.004) in males and females combined. When the association was stratified by IBD subtype, the association remained for UC but not CD.

Conclusion
Pro-inflammatory predicted hs-CRP score (derived from diet and lifestyle characteristics) was associated with higher odds of IBD, particularly among IBD cases presenting with UC. Promoting lifestyle modification to avoid pro might be promising for the primary prevention of IBD.
P948 Hand Grip Strength is a useful objective measure associated with fatigue and impaired quality of life in patients with inflammatory bowel disease
Authors: Stack R , Ní Chonnacháin C , Doherty J , O'Moran N , Girod P , Noronha N , Gibney E R , Doherty G A 
Published: January 2024

Abstract

Background
Hand grip strength (HGS) is a recognised tool for diagnosis / screening of muscle impairment and sarcopenia, however it remains underutilised in IBD cohorts. The aim of the study was to measure the prevalence of muscle impairment by HGS and association with quality of life in a cohort of UC patients in disease remission.

Methods
Potential subjects were prospectively identified for selection from the Gastroenterology Department in St. Vincent’s University Hospital Outpatient Department. All patients had a confirmed diagnosis of UC for &gt;3 month with stable, quiescent disease (no escalation of medical therapy in the previous 3 months with a documented Faecal Calprotectin (FCP) &lt;100 μg/g). Along with anthropometry data, HGS measurements were performed using the Jamar®Plus+Dynamometer. Quality of life scores were measured using 36-item Short Form Survey (SF-36), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and Short Health Scale questionnaires were measured. Linear regression was used to calculate standardised β-coefficients for correlation analysis. Non-parametric data was analysed using algorithms including Kruskal-Wallis and Wilcoxon rank-sum test.

Results
60% (n=18) of subjects had a HGS outside the lower limit of the 95% confidence interval of age and sex matched normative values, indicative of impaired grip strength. This was significantly more prevalent in subjects with normal BMI than BMI&gt;30 (p=0.035). Prevalence of fatigue was 43.3% according to SIBDQ question 2a and ’Energy/Fatigue’ scores of SF-36 were significantly lower compared to normal Irish population data (51.0 v 64.8, p = 0.0002). Composite scores of fatigue in both SIBDQ (question 2a) and SF-36 were compared, resulting in a standardized β-coefficient of 0.52 of statistical significance (p value = 0.003).Significant correlation was demonstrated between predicted HGS and ’Energy/Fatigue’ SF-36 scores (standardised β-coefficient = 0.4, p value = 0.027).

Conclusion
HGS is a convenient means of measuring muscle function in an IBD population and correlates significantly with ’Energy/fatigue’ SF-36 scores. These results suggest sarcopenia as a potentially important contributor to fatigue in patients with IBD and suggest HGS is an objective, easily applied objective measure which merits validation as an outcome measure for intervention studies to improve fatigue in patients with IBD.