bluuebunny/crossref_metadata_2025_split huggingface dataset:
P610 Ustekinumab demonstrates superior treatment persistence over anti-TNF in Crohn’s disease patients previously treated with vedolizumab
Authors: Chiu H Y , Le P H , Yeh P J , Kuo C J , Lai M , Wu R C , Chen C M , Chiu C T , Chiu C H , Su M , Pan Y B 
Published: January 2024

Abstract

Background
With the rise in biologic therapies to manage moderate to severe inflammatory bowel disease (IBD), determining the optimal treatment sequence has become crucial. This aids in the selection of the next biologic agent after prior exposure or unresponsiveness to a previous regimen. Vedolizumab (VDZ) is a gut-specific α4β7-integrin inhibitor recognized for its efficacy in treating moderate to severe IBD. Yet, only a few studies have assessed the comparative effectiveness of alternative biologics, such as ustekinumab (UST) and antitumor necrosis factor agents (anti-TNF), following VDZ exposure.

Methods
In our retrospective study conducted at Chang Gung Memorial Hospital at Linkou, a leading 3700-bed medical facility in Taiwan, we examined 110 IBD patients who underwent treatment with UST or anti-TNF agents (including adalimumab and infliximab) from May 2019 to September 2023. UST's standard maintenance dosing in Taiwan is every 12 weeks. We utilized Kaplan-Meier analysis and Cox proportional hazards models to evaluate the 52-week treatment retention of UST versus anti-TNF.

Results
Of the 110 participants, 40 were diagnosed with ulcerative colitis (UC), and 70 with Crohn’s disease. The demographics between the anti-TNF and UST groups regarding age, gender, and body mass index were comparable. The primary reason for vedolizumab discontinuation in both groups was secondary non-response (Table 1). UST exhibited a notably higher 52-week retention in overall IBD (HR: 5.36, 95% CI: 1.84-15.62, P = 0.002, Figure 1a) and in Crohn’s disease patients (HR: 10.75, 95% CI: 1.34-86, P = 0.025, Figure 1b) compared to anti-TNF. While UST also showed superior persistence at 52 weeks in UC patients, the difference was not statistically significant (HR: 2.25, 95% CI: 0.63-8, P = 0.211, Figure 1c). At the 52-week mark, 73.5% of the anti-TNF group and 81% of the UST group were not on steroids. Secondary non-response was the predominant cause for discontinuation of the current biologic. Notably, UST required more frequent dose adjustments than anti-TNF. The safety profile of both treatments was comparable.

Conclusion
UST showed superior treatment persistence, compared to anti-TNF in Crohn's disease patients who had previously been exposed to vedolizumab. However, UST required more frequent dosing adjustments compared to anti-TNF.
P683 Economic impact of achieving mucosal healing on UC-related hospitalisations and work productivity in patients with moderately to severely active UC: A post-hoc analysis of risankizumab Phase 2b/3 trials
Authors: Peyrin-Biroulet L , Ungaro R , Rubin D T , Bokemeyer B , Ricart E , Levine P , Lai J H , Sharma D , Vladea R , Sanchez Gonzalez Y , Patel K 
Published: January 2024

Abstract

Background
The value of endoscopic-histologic healing is incompletely understood, and definitions are variable. We assessed the clinical and economic value of achieving mucosal healing in patients with ulcerative colitis (UC) by evaluating the relationship of histologic-endoscopic mucosal improvement (HEMI) and subsequent UC-related hospitalisation and work productivity, and associated costs in the United States (US); United Kingdom (UK); and France, Germany, Italy, and Spain (EU4).

Methods
Data from the risankizumab (RZB) INSPIRE induction (NCT03398148) and COMMAND maintenance (NCT03398135) studies were analysed. The number of UC-related hospitalisations was compared in patients who achieved HEMI or no HEMI using a chi-square test. The mean percent changes in Work Productivity and Activity Impairment (WPAI)-UC domains from baseline to induction week 12 and maintenance week 52 were compared in patients who achieved HEMI or no HEMI using analysis of variance test. Hospitalisation and work productivity differences during induction and maintenance were converted to annualised costs based on average earnings and hospitalisation cost inputs from US, UK, and EU4.

Results
UC-related hospitalisations were significantly lower in patients who achieved HEMI at induction week 12 than those who did not (0% vs 2.9%, p≤0.05). A similar result was found at maintenance week 52, but the difference was not significant. In patients who achieved HEMI vs no HEMI, a greater mean change in activity impairment, impairment while working, and overall work impairment from baseline to induction week 12 was observed (p≤0.001). Improvements were sustained at maintenance week 52 for patients who achieved HEMI vs those who did not. Estimated annualised cost benefits from maintenance data for UC-related hospitalisations in patients who achieved HEMI was $490 in the US, £29 in the UK, and €28–€58 in EU4. Greater monetised benefits accrued from work productivity gains, where estimated annualised cost savings were $5,085 in the US, £3,507 in the UK, and €3,240–€4,456 in EU4.

Conclusion
These findings demonstrate that patients treated with RZB who achieved HEMI had fewer UC-related hospitalisations and greater improvement in work productivity and ability to perform daily activities than those who did not, which results in moderate direct cost savings and substantial indirect cost savings to healthcare systems in the US, UK, and EU4.
P775 Efficacy and safety of risankizumab in children with Crohn’s disease: A preliminary report
Authors: Spencer E , Stein R , Shalem T , Zifman E , Dubinsky M , Lev Tzion R , Turner D , Assa A 
Published: January 2024

Abstract

Background
Risankizumab (RISA) is a selective p19 anti-interleukin (IL)-23 antibody approved for adults with Crohn’s disease (CD) and for children ≥ 16 years in selected countries. Given delays in pediatric approvals, we aimed to assess the real-world effectiveness and safety of RISA in pediatric patients with CD.

Methods
From September 2022 to November 2023, all pediatric patients (&lt;18 years) with refractory CD treated with RISA in 5 centers from US and Israel were retrospectively included. All received a 600 mg RISA intravenous induction at weeks 0-4-8. Patients completing the induction phase were treated with subcutaneous injection of 360mg at week 12 and every 8 weeks thereafter. The primary endpoint was steroid-free clinical remission (SFR) after 3 intravenous infusions (i.e., wPCDAI ≤12.5). Secondary endpoints included clinical response (i.e., &gt;17.5-point decrease of wPCDAI), biochemical remission (CRP ≤ 5 mg/L) and drug sustainability. Adverse events were explicitly recorded.

Results
Included were 23 children [13 (56%) males; mean age at diagnosis 14.1±3.7 years, median disease duration 3.9 (IQR 2.6-7.7) years, 11 (48%) &lt; 16 years of age] with a median follow-up period of 21 weeks (IQR 9.4-44.2) (Table 1). All had failed at least one previous biologic treatment and 18 (78%) failed two, including 15 (65%) with prior ustekinumab treatment. After 3 infusions, SFR was observed in 15 (65%) children, clinical remission in 16 (70%), clinical response in 17 (74%), and CRP remission in 17 (74%). There was no difference in response rate of patients &lt;16 years (64% SFR). In a subgroup analysis of 15 patients with prior ustekinumab exposure, SFR was observed in 11 (73%). Only two patients discontinued RISA during follow-up, one who was in clinical and CRP remission at week 12, due to loss of follow-up and the other due to occurrence of an intra-abdominal abscess. Ten patients completed 6 months follow-up, of whom 8 (80%) achieved SFR by then. Only one disease-related adverse event occurred in one patient (intra-abdominal abscess). No drug-related adverse events were recorded.

Conclusion
While awaiting pediatric registration trials, our preliminary data suggest that RISA is safe and effective in inducing and maintaining remission in children with highly-refractory CD. This includes also children previously failing ustekinumab and children younger than 16 years.
P812 Whole Food and Antioxidants Consumption Linked to Lower Risk of Inflammatory Bowel Disease in Taiwan
Authors: Meng M J , Huang J , Le P H , Pan Y B , Chiu C T , Lin Y T 
Published: January 2024

Abstract

Background
The incidence of inflammatory bowel disease (IBD) rapidly increases in Asia, and western dietary pattern is suspected to be the major risk factor. Despite this, there has been a lack of studies analyzing the relationship between dietary patterns and IBD in Taiwan. This study examines the dietary habits of Taiwanese individuals with and without IBD to inform clinical dietary recommendations for IBD patients.

Methods
A comprehensive survey utilizing structured questionnaires to collect baseline characteristics and dietary information from both IBD patients and healthy controls from February and August 2022. The dietary habits of IBD patients in this study were focused on the three months leading up to their IBD diagnosis. Numerical data were presented as mean ± standard deviation, while categorical data were expressed as absolute numbers and percentages. Statistical analysis involved the Mann–Whitney U test for continuous variables and the chi-square or Fisher's exact test for categorical data. Statistical significance was defined as p &lt; 0.05, and all analyses were performed using SPSS version 22.0.

Results
Our study included 98 IBD patients, with 46 diagnosed with Crohn's disease and 52 with ulcerative colitis, along with 184 healthy controls. Notably, in terms of baseline characteristics, the IBD group exhibited a significantly higher prevalence of cigarette smokers compared to the control group (29.5% vs. 12.6%, p = 0.001). Regarding dietary habits, IBD patients reported consuming significantly fewer natural food categories compared to the control group. These differences included lower consumption of rice products (p = 0.005), cereal products (p &lt; 0.001), mixed-grain products (p &lt; 0.001), mushrooms (p = 0.004), burdock (p = 0.001), poultry (p = 0.049), and milk (p &lt; 0.001). Intake of red meat, seafood, and nuts was comparable. Concerning processed food products, IBD patients also reported less frequent consumption of soymilk (p = 0.017), mock meat (p = 0.012), and tea (p = 0.043). In terms of dietary supplements, IBD patients were less likely to use vitamin supplements (C or E) compared to healthy controls (25% vs. 42.4%, p = 0.004), and they also reported lower consumption of soybean lecithin (1% vs. 7.6%, p = 0.02). The baseline characteristics, frequency of natural foods, processed foods and dietary supplement consumption were summarized in Table 1.

Conclusion
The findings of our study suggest that a diet rich in whole foods and antioxidant may be associated with lower risk of IBD in Taiwan. However, it’s important to note that further research with a larger sample size is necessary to confirm these observations and provide more robust insights into the relationship between dietary factors and IBD.
P816 Baseline disease severity of patients with Ulcerative Colitis influences rapid symptom relief under filgotinib treatment: post hoc analysis of the phase 2b/3 SELECTION study
Authors: Saruta M , Danese S , Takatori Y , Kaise T , Rudolph C , Ferrante M , Hibi T 
Published: January 2024

Abstract

Background
Filgotinib (FIL) is an oral, once-daily, Janus kinase 1 preferential inhibitor approved in Europe and Japan for the treatment of ulcerative colitis (UC). A recent analysis of SELECTION trial data (NCT02914522) showed rapid and sustained improvements in UC symptoms with FIL 200 mg (FIL200) treatment in patients with moderate-to-severe UC.1 Here we assess symptomatic remission rates over time with FIL200 induction treatment according to baseline UC disease severity (partial Mayo Clinic Score [pMCS]).

Methods
SELECTION was a phase 2b/3 randomized, double-blind, placebo-controlled study. Patients aged 18–75 years were randomized (2:2:1) to receive FIL200, FIL 100 mg or placebo once daily for 11 weeks in induction study A (biologic-naive patients) or induction study B (biologic-experienced patients). In this post hoc analysis, proportions of patients with symptomatic remission (Mayo rectal bleeding sub-score of 0 and Mayo stool frequency sub-score of ≤ 1), from days 2 to 15 and weeks 2 to 10 of the induction study, were analysed at each timepoint by baseline pMCS (pMCS ≥7 and pMCS &lt;7 [cut-off previously used for severe and moderate disease, respectively]2). Symptomatic remission rates were compared between the pMCS ≥7 and pMCS &lt;7 groups within the FIL200 and placebo arms using a Cochran–Mantel–Haenszel test adjusted by study randomization stratification factors. Nominal p values &lt;0.05 were considered statistically significant.

Results
At day 2, symptomatic remission rates with FIL200 treatment were significantly higher in patients with baseline pMCS &lt;7 than in those with baseline pMCS ≥7 (8.4% vs 1.1%, p=0.009 [induction study A]; 8.8% vs 0.7%, p=0.004 [induction study B]) (Figure A and B). From days 2 to 15, symptomatic remission rates increased in both groups and, except for day 7 for induction study A and day 9 for induction study B, continued to be significantly higher in those with baseline pMCS &lt;7. From week 2, symptomatic remission rates with FIL200 treatment generally continued to increase in both pMCS ≥7 and pMCS &lt;7 groups (Figure C and D). By week 10, symptomatic remission rates with FIL200 treatment were no longer significantly different between those with baseline pMCS &lt;7 and those with baseline pMCS ≥7 (54.8% vs 43.3%, p=0.124 [induction study A]; 39.5% vs 26.4%, p=0.099 [induction study B]).

Conclusion
Symptomatic response to FIL200 occurs more rapidly in patients with lower UC disease severity than in those with higher UC disease severity. However, converging response rates over 10 weeks of treatment leads to symptomatic remission regardless of baseline UC disease severity.
References
1. Danese S et al. Am J Gastroenterol 2023;118(1):138–47
2. Panés J et al. J Crohns Colitis 2019;13:1148–57
P823 Real-world effectiveness of upadacitinib in Crohn's disease; a UK multicentre retrospective cohort study
Authors: Elford A , Bishara M , Plevris N , Gros B , Constantine-Cooke N , Goodhand J , Kennedy N , Ahmad T , Lees C 
Published: January 2024

Abstract

Background
Upadacitinib is a Janus kinase inhibitor which has recently been approved for the treatment of Crohn’s disease. There are limited real-world studies on the outcomes of upadacitinib in Crohn’s disease. Our aim was to evaluate the outcomes of upadacitinib in a real-world cohort.

Methods
We conducted a retrospective, multicentre, cohort study. Our primary outcome was treatment persistence at week 24. Our secondary endpoints were corticosteroid-free clinical remission (Harvey-Bradshaw Index ≤4), and biomarker remission (CRP ≤5 mg/L and FCAL &lt;250 µg/g). We measured outcomes at 12 weeks, 24 weeks and at last observation. We recorded adverse events.

Results
We included 74 patients who commenced upadacitinib over a two-year period for analysis, with a median follow-up time of 23 weeks (IQR, 15-39 weeks). All patients had failed anti-TNF therapy, with 78% and 58% additionally failing prior IL12/23 and vedolizumab (Table 1). Treatment persistence was 83.6% at week 12, and 76.6% at week 24 (Figure 1). Reasons for treatment cessation included primary non-response 15% (11/74), secondary loss of response 1% (1/74), and adverse events 12% (9/74). Rates of clinical remission were 58% (32/55) at week 12, 43% (16/37) at week 24, and 52% (35/67) at last observation. CRP remission rates were 45% (27/60) at week 12, 35% (12/34) at week 24, and 44% (30/69) at last observation. FCAL remission rates were 40% (17/42) at week 12, 31% (9/29) at week 24, and 36% (19/53), at last observation. There was a significant reduction in HBI, CRP and FCAL during follow-up (Figure 1). During the maintenance period, 11% (7/61) of the cohort who continued therapy were prescribed corticosteroids. Ten patients (19%) had a hospitalisation due to a Crohn’s flare. Five patients (7%) underwent Crohn’s disease related resectional surgery during the study period. Two were emergency surgeries (3%), and three (4%) were elective surgeries for symptomatic fibrotic strictures, which were present prior to commencing upadacitinib. Thirty-four adverse events were recorded across 29 patients (39%). Serious adverse events occurred in 9 patients (12%), three of which (4%) led to hospitalisation.

Conclusion
Upadacitinib was effective in a real-world, medically refractory, moderate to severe Crohn’s disease cohort with good persistence.
P825 Comprehensive dietitian-delivered dietary advice effectively achieves dietary change in adults with Ulcerative Colitis, whereas generalised written dietary advice does not
Authors: Portmann L , Bryant R , Raja S , Rayner C , Telfer K , Costello S , Day A 
Published: January 2024

Abstract

Background
Diet is an important consideration in microbial therapy trials. It is unclear whether provision of generalised written dietary advice is sufficient to induce dietary change as part of a therapeutic regimen or whether personalised diet advice is required. This study examines the effectiveness of different dietary advice modes provided in dietary and faecal microbiota transplantation (FMT) studies in adults with mild-moderately active ulcerative colitis (UC).

Methods
This observational study examined before and after dietary intake data from three prospective dietary and FMT studies held from 2018 to 2021 at a South Australian tertiary inflammatory bowel disease service. In all studies, adults ≥18 years with mild-moderately active UC completed 3 or 7-day weighed food diaries measuring habitual diet at 0 and 8 weeks after provision of dietitian-developed dietary advice. In studies one and two, a medical officer provided participants a written UC healthy eating pamphlet. The pamphlet contained generalised dietary recommendations for UC, targeting reduction of total and animal protein and increasing fermentable fibres including resistant starch to recommended serve sizes. In study three, a research dietitian provided a 1-week guided meal plan, diet manual with recipes and verbal personalised dietary counselling advising on the same recommendations and strategies. In all studies, participants were encouraged to eat to appetite. Dietary intake, including key nutrients of interest (protein and fermentable fibres), at weeks 0 and 8 was assessed using Foodworks 10TM nutritional analysis software and analysed using paired statistical tests.

Results
Across studies one and two, 28 adults with mild-moderately active UC received written dietary advice. In study three, 30 adults received personalised verbal and written dietary advice. Outlined in Table 1, verbal and written advice significantly reduced total protein and animal protein intakes by 20% (p=0.007) and 34% (p=0.002) respectively. Total fibre and resistant starch intakes significantly increased by 64% (p&lt;0.001) and 353% (p&lt;0.001) respectively. Comparatively, written advice alone had no significant change on any key nutrient intakes. Neither dietary advice mode significantly changed energy or micronutrient intakes.

Conclusion
Written dietary advice alone was insufficient to achieve dietary change. In contrast, verbal and written dietary advice with the same intended change on dietary intake, delivered by a research dietitian effectively achieved dietary changes. This emphasises that comprehensive written and verbal dietary education delivered by a dietitian should be included in microbial-modulating study designs where dietary change is an intended outcome.
P846 Impact of 5-ASA discontinuation in children with ulcerative colitis under biological therapy
Authors: D'Arcangelo G , Di Bari E R , Distante M , Rotulo S , Brecciaroli M , Catassi G , Aloi M 
Published: January 2024

Abstract

Background
Mesalamine (5-ASA) is recommended as a first-line medication for inducing and maintaining remission in mild to moderate ulcerative colitis (UC), but indications regarding its use in children with moderate to severe disease treated with biologics are lacking. We aimed to evaluate whether discontinuing 5-ASA might impact the outcomes of children with UC treated with anti-TNFα.

Methods
Retrospective, single-center, case-control study of children with UC receiving anti-TNFα therapy between January 2018 and January 2023 and with a minimum follow of 6 months. Children who discontinued 5-ASA within six months from the biological therapy initiation were compared to those who continued mesalamine as maintenance therapy. Every 6 months, during a 2-year follow-up, major outcomes defined as disease flares, IBD-related hospitalization, surgery, need for step-up treatment were recorded.

Results
Ninety-eight children were included in the final analysis, 51 (52%) maintained 5-ASA and 47 (48%) discontinued 5-ASA. The 2 groups were comparable for all the baseline clinical and demographic characteristics. At 6 months, the cumulative incidence of major outcomes, acute severe colitis and need for step up treatment was significantly higher in children who discontinued 5-ASA (p &lt; 0.05). Throughout the follow-up period, children who discontinued 5-ASA were at significant higher risk of hospitalization (Log Rank p=0.02), need for step up treatment (Log Rank p=0.02) and acute severe colitis (Log Rank p=0.003).

Conclusion
Our data suggest that 5-ASA discontinuation might have a negative impact on the clinical course of children with UC treated with anti-TNFα in terms of major outcomes. However, conclusive evidence regarding this matter requires prospective randomized trials.