bluuebunny/crossref_metadata_2025_split huggingface dataset:
P1014 Faecal loss of vedolizumab is associated with UC severity, lower serum vedolizumab levels and rates of clinical response – Results from the FAVOUR study
Authors: Samaan M , Cunningham G , Lim S , Dawson P , Kottoor S H , Bheekhun Z , Anderson S , Mawdsley J , Ray S , Powell N , Dart R , Rawstron K , Arkir Z , Irving P M 
Published: January 2024

Abstract

Background
Infliximab is detectable in the faeces of patients with active UC and faecal loss is associated with more severe disease and with primary non-response. Detection of vedolizumab (VED) in faeces and its importance in patients with UC has not been investigated. We conducted a prospective, observational study of patients with UC commencing VED to investigate faecal VED loss as well as its impact on serum VED levels (SVL) and association with treatment outcomes.

Methods
The FAVOUR study recruited UC patients with moderate to severe UC commencing vedolizumab between April 2019 and May 2022. Patients were treated with 300mg VED IV at weeks 0, 2, 6 and 14. Trough SVL were measured at weeks 2, 6 and 14. Faecal samples at days 1, 4, 7 and at weeks 2, 6 and 14 were homogenised and centrifuged to produce supernatants which were analysed for faecal VED levels (FVL) using a commercially available ELISA (LISA TRACKER, Theradiag, France).
Clinical (SCCAI) and biochemical disease activity (CRP and faecal calprotectin) were measured at each infusion. Endoscopy was performed at baseline and week 14 to measure endoscopic (UCEIS/Mayo) and histologic activity (NHI).
Correlations were calculated using the Spearman correlation coefficient (r). Categorical variables were compared using Mann-Whitney U.

Results
36 patients (median age 34 (range 18-73); 13 Female) were recruited, of whom 33 completed induction therapy (3 withdrew early and were considered non-responders). 26/36 (72%) achieved a clinical response (SCCAI≤5 and reduction of ≥2) and 18/36 (50%) achieved endoscopic remission (UCEIS≤2).
Faecal VED was detectable in 80/203 (39%) samples. Statistically significant correlations were observed between FVL and markers of clinical, biochemical, baseline endoscopic and histologic disease activity at day 1, and weeks 2 and 6 (table 1). Week 14 clinical non-responders had higher FVL than responders at that time point (median 1.0 vs 0.0ug/mL, p=0.004) but not at other timepoints. A statistically significant negative correlation was observed between week 2 FVL and SVL measured at weeks 6 and 14 (table 1). SVL did not differ significantly between week 14 responders and non-responders at any time point.

Conclusion
Active colonic inflammation results in faecal loss of vedolizumab. This appears to correlate with lower SVL and rates of response to treatment. However, SVL were not observed to directly influence rates of response. It is possible that FVL may be a marker of disease activity or that faecal loss results in lower rates of drug exposure at a tissue level and negatively impacts rates of response by this mechanism.
P1039 RECtal OUtcomes in Paediatric Ulcerative Colitis (RECOUP-UC): An International Clinical Practice Survey of Paediatric Gastroenterologists
Authors: Gordon B , Cooper S , Bourke B , Hussey S 
Published: January 2024

Abstract

Background
Ulcerative Colitis (UC) in childhood is associated with a higher risk of developing acute severe colitis and colectomy compared to adult populations. Following subtotal colectomy, the rectal remnant is typically oversewn and remains in-situ until ileal continuity surgery is undertaken. Access to such surgical expertise determines the timing of restorative surgery, which may range from months to years. There is a paucity of data regarding residual rectal activity during this interval, its medical management and clinical outcomes.

Methods
An electronic survey (SurveyMonkey) of clinical practice was disseminated to the paediatric inflammatory bowel disease (PIBD) community internationally. Data collected included treating centre demographics, local colectomy practices, expert opinion on rectal cuff assessment and management. Clinicians were asked to rank order the symptoms and signs considered most relevant to determining disease activity. They also ranked the clinical features they believed most important to patients. Descriptive statistics were used to present findings.

Results
Responses were collated from over 10 countries, including Ireland, Sweden, UK, Australia, Israel, Canada, Iran, Finland, UAE and Austria. Centre sizes were categorised based on total PIBD population. There was heterogeneity across centres - 16% of respondents were from small volume centres in the range of 0-100 patients, 45% were from medium sized centres (101-300), 25% were from large volume centres (301-500) and 12% treat &gt;500 patients which we categorised as very large volume. Despite variation in centre volume majority of respondents (75%) diagnose &gt;20 new cases of UC annually.
Over 90% of respondents reported having no formal guideline for managing rectal disease. Most centres’ patients (60%) waited at least 3 months post-colectomy for restoration surgery. Mild intermittent symptoms were expected to continue by 60% of respondents. Of these symptoms, 45% ranked haematochezia as the most important in determining severity. There was no consensus on the best assessment tool to use; 30% use the PUCAI. Most (80%) use blood markers and endoscopy routinely to assess rectal activity. Favoured treatments include rectal therapy (80%) followed by oral steroids and surgical referral. All respondents agreed that additional research was needed.

Conclusion
International management of the rectum following subtotal colectomy in children is characterised by variable clinical practises, and a lack of guidelines or validated assessment tools. Additional research in the field is needed to address current literature deficits and improve care for children.
P1049 Effectiveness and safety of subcutaneous infliximab in Crohn’s disease patients with immunogenic failure of intravenous infliximab
Authors: Husman J , Černá K , Matthes K , Gilger M , Arsova M , Schmidt A , Winzer N , Brosch A M , Hampe J , Zeissig S , Lukáš M , Schmelz R 
Published: January 2024

Abstract

Background
Immunogenicity is a major reason for secondary loss of response to infliximab (IFX). Recent work suggested potentially lower immunogenicity of subcutaneous compared to intravenous infliximab. However, it is unknown whether re-exposure of patients with immunogenic failure of IFX to its subcutaneous formulation is safe and effective. Here, we analysed the safety and effectiveness of subcutaneous IFX (CT-P13) in patients with Crohn’s disease (CD) and history of secondary loss of response of intravenous IFX due to anti-drug antibodies (ADA).

Methods
In a retrospective analysis conducted at medical centers in Germany (Dresden) and the Czech Republic (Prague), patients with clinical (Harvey-Bradshaw Index ≥ 5) and/or biochemical (faecal calprotectin &gt;250 µg/g) active CD and previous treatment failure in the context of IFX immunogenicity underwent re-exposure to subcutaneous IFX. Treatment was initiated with either 4 subcutaneous injections 120 mg CT-P13 weekly followed by biweekly injections, or directly with 120 mg CT-P13 subcutaneous biweekly. Harvey-Bradshaw Index, faecal calprotectin, IFX serum concentration and ADA were assessed until month 12.

Results
Twenty CD patients were included (table 1). The majority of patients (90 %) had previous treatment with ≥ 3 biologics. 75% and 50 % of patients continued IFX treatment until month 6 and 12, respectively. No immediate hypersensitivity reactions were observed. Two patients (10%) discontinued IFX due to delayed hypersensitivity. Lack of treatment effectiveness led to infliximab withdrawal in 7 cases (35%) and one patient (5%) was lost to follow up after month 6. IFX serum concentrations increased from baseline (median 0 µl/ml ± 0 interquartile range/IQR) until month 12 (median 22.8 µl/ml, 10.0 IQR), while ADA levels decreased (50.6 AU/ml, 48.3 IQR and 0.0 AU/ml, 0 IQR at baseline and month 12, respectively). Clinical remission at month 12 was observed in 27% and biochemical remission in 38% of patients with active Crohn's disease at baseline. 67 % of patients with clinical inactive Crohn's disease at baseline remained in clinical remission until month 12.

Conclusion
Subcutaneous infliximab after previous failure and immunogenicity of intravenous infliximab was well tolerated and effective in a cohort of patients with refractory Crohn’s disease.
P1070 Utilization of HLA-DQA1*05 haplotype testing in routine clinical practice to stratify advanced therapies: A prospective pilot study
Authors: Ibrahim F A E , Aleman Gonzalez H , Whitehead E , Robertson H , Fitzgerald A L , Turnbull J , Messiha M , Thomas M , Sebastian S 
Published: January 2024

Abstract

Background
A potential association between HLA-DQA1*05 allele and development of anti-drug antibodies in Anti-TNF treated Crohn’s Disease patients is reported in the PANTS study. The utility of stratifying treatment based on the HLA-DQA1*05 status has not been evaluated in a biomarker stratified clinical trial and there are no prospective studies evaluating the impact of using HLADQA1*05 in routine clinical practice to decide on monotherapy versus combo therapy while initiating on anti-TNFs. We aimed to determine the impact of carriage of HLADQA1*05 allele to guide the need for concomitant immunomodulators in IBD patients planned for Infliximab therapy.

Methods
In our prospective study, 97 adult IBD patients were included. All patients were screened for HLADQ2 haplotype as part of their routine pre-biologic screen. Stratification was done according to the presence of HLA-DQA1*05 haplotype. HLADQA1*05 positive patients were assigned combo therapy with Infliximab combined with either methotrexate or azathioprine. HLADQA1*05 negative patients were given infliximab monotherapy unless another indication for concomitant immunomodulation was present. Patients were followed for a minimum of one year after drug initiation. Primary outcome was drug persistence, expressed as time to discontinuation of infliximab, segregated by the treatment decision based on HLA-DQA1*05 status. Secondary outcomes were proportion of patients developing anti-drug antibodies and time to antibody development. Statistical analysis was done using Kaplan-Meier curves and log-rank test.

Results
Baseline characteristics are detailed in Table 1. HLA-DQA1*05 was positive in 41/97(42%) of patients and combo therapy was offered to 33/41(80%) of those patients. Immunomodulators were avoided in 39/97(40.2%) patients representing the subset of patients with negative HLADQA*105 to whom no immunomodulator was offered. There was no statistically significant difference in drug persistence rates between the groups treated based on HLA-DQA*105 status. 54/97(55.6%) of the patients developed anti-infliximab antibodies during their follow-up (25/41(60.9 %) in HLA positive and 29/56 (51.7%) in HLA negative). Neutralizing drug antibodies with absent drug levels were detected in 15/97(15.5%) of patients (8/41(19.5%) in HLA positive, 7/56(12.5%) in HLA negative). The median time to antibody development was 33.5 weeks (IQR 22-46.7).

Conclusion
This is the first prospective study suggesting HLA-DQA1*05 haplotype testing can be used in routine clinical practice to stratify therapy based on the need for immunomodulators in infliximab treated IBD patients. HLA-DQA1*05 negative patients may be started on monotherapy with potential for improving safety and reducing costs of immunomodulator monitoring.
P1073 Opioid use Before and After First Diagnosis of Crohn’s Disease: A Swedish Nationwide Cohort Study 2008-2020
Authors: Osooli M , Bruze G , Bryder N , Nordenvall C , Myrelid P , Everhov Å H , Olén O 
Published: January 2024

Abstract

Background
The ongoing opioid misuse epidemic, initially sparked by over-prescription, presents challenges in managing severe pain in Crohn’s disease (CD). Despite associated negative effects, such as narcotic bowel syndrome and susceptibility to chronic use, opioids are frequently prescribed for CD patients. However, data on the evolution of opioid use before and after the initial CD diagnosis in a European context are limited.

Methods
This nationwide cohort study utilized the Swedish Patient Register to identify adults with a first CD diagnosis between 1 January 2008 and 31 December 2017, residing in Sweden at least two years before and three years after the diagnosis. For each CD patient, we included up to 10 reference individuals from the general population matched on birth year, sex, calendar year, and place of residence. Data on dispensed opioid prescriptions were retrieved from the National Prescribed Drug Register. Opioid use history was categorized into non-users (no dispensations), intermittent users (≥1 dispensation in 1–3 periods), and chronic users (≥1 dispensation in all periods) based on the four preceding six-month periods before the first CD diagnosis. Opioid use per six-month period was estimated from two years before to five years following CD diagnosis (corresponding index date for matched reference individuals) and coarsened exact matching was employed to account for confounding (birth year, sex, education, and history of psychiatric disorders and cancer).

Results
We included 12,539 incident CD patients and 116,073 matched reference individuals. During the two years before the first CD diagnosis, CD patients (and 3.9% vs 10.4% and 1.4%, respectively) were more often intermittent (22.3% vs 10.4%) or chronic (3.9% vs 1.4%) opioid users than matched reference individuals. Prior to diagnosis, opioid use per six-month period was twice as common among CD patients than in reference individuals. Following a peak in the first year after the diagnosis, the prevalence of dispensed opioids per six-month period stabilized at a three-fold level among CD patients (13.6%; 95% CI: 13.0, 14.3) compared with the reference individuals (5.5%; 95% CI: 5.4, 5.7) (Figure 1). The 6-month prevalence of opioid use five years after CD diagnosis was 7.6% (95% CI: 7.0, 8.2), 22.9% (95% CI: 21.1, 24.6), and 79.5.4% (95% CI: 73.2, 85.7) for CD patients classified as non-users, intermittent, or chronic users two years before diagnosis, respectively.

Conclusion
CD patients exhibited elevated opioid use two years before their initial diagnosis, which persisted at a three-fold level compared to matched reference individuals for five years post-diagnosis. This pattern persisted despite publicly-funded healthcare and modern CD therapy accessibility.
P1082 A comparative analysis of persistence of advanced therapies among patients with Inflammatory Bowel Disease in Taiwan
Authors: Chiu H Y , Le P H , Kuo C J , Lai M W , Wu R C , Chen C M , Chiu C T , Chiu C H , Su M , Pan Y B 
Published: January 2024

Abstract

Background
The prevalence of inflammatory bowel disease (IBD) has been rapidly increasing in Asia. Advanced therapies have significantly improved outcomes for moderate to severe cases of IBD. With the expanding availability of advanced therapies, the selection of the most suitable treatment option has become crucial. Among various factors, treatment persistence holds paramount importance. We present the first study in Asia that compares real-world persistence rates among advanced therapies in IBD patients in Taiwan.

Methods
In this retrospective cohort study, we enrolled patients with IBD who were treated with five advanced therapies: infliximab (IFX), adalimumab (ADA), vedolizumab (VDZ), ustekinumab (UST), and tofacitinib (TOF) at Linkou Chang Gung Memorial Hospital between October 2017 and April 2023. UST followed a standard maintenance dosing frequency of every 12 weeks, while TOF was permitted for use only as a second-line treatment option for UC in Taiwan. We compared baseline data and drug persistence rates within the first 52 weeks for the overall group, biologic-naïve patients, and biologic-experienced patients.

Results
A total of 432 IBD patients were included, with 173 (40%) having ulcerative colitis (UC) and 259 (60%) having Crohn's disease (CD). The majority of patients were male, with a mean age of 43.6 years and a mean BMI of 22.6. UST showed the highest rate of dose escalation (22%). Across all five drugs, the primary reason of discontinuation was secondary loss of response, with IFX having the highest discontinuation rate due to side effects (20%). Other baseline characteristics were presented in Table 1.
Kaplan-Meier analysis revealed that all biologics exhibited a persistence rate of over 50% within the initial 52 weeks. UST demonstrated the highest 52-week persistence rates in overall (87.88%, p &lt; 0.001, Figure 1a), biologic-naïve (96.55%, p = 0.002, Figure 1b) and biologic-experienced CD patients (80.56%, p=0.043, Figure 1c). Although no statistically significant differences were observed between advanced therapies in overall UC patients and other subgroup analyses (Figure 1d-1f). VDZ showed highest 52-week persistence in overall (69.05%, p=0.078, Figure 1d) and biologic-experienced (60.87%, p=0.751, Figure 1f) UC patients. UST had highest 52-week persistence in biologic-naïve UC patients (100%, p=0.329, Figure 1e).

Conclusion
In this pioneering real-world comparison of advanced therapies across one year in Asia, UST exhibited superior 52-week persistence rates in CD patients. However, the rate of dose escalation in UST was also the highest among these therapies. The study's limitations include its single-center nature and relatively small sample size.
P1090 Exposure to an inflammatory prenatal environment and the risk of Inflammatory Bowel Disease in the offspring: a population-based cohort study
Authors: Bonfils L , Poulsen G , Agrawal M , Julsgaard M , Torres J , Jess T , Allin K 
Published: January 2024

Abstract

Background
The strongest independent risk factor for developing Inflammatory Bowel Disease (IBD) is a family history with IBD. The early life, including the intra-uterine period, is critical for immune system maturation and therefore, exposures during early life can influence IBD risk. We conducted this study to understand if the risk of IBD in the offspring of women with IBD is due to an inflammatory prenatal environment in addition to genetic predisposition.

Methods
Using cross-linked nationwide Danish health registers, we identified all individuals born in Denmark from 1997 to 2022 as well as their legal parents. Of these, we identified all individuals diagnosed with IBD and the date of diagnosis. The follow up period was from the date of birth until date of IBD diagnosis, death, emigration, or August 1, 2022, whichever occurred first. We performed Cox proportional hazards analyses adjusted for calendar period to assess the risk of IBD in individuals born of mothers diagnosed with IBD before childbirth, those diagnosed with IBD after childbirth, and those with no IBD diagnosis. Since paternal IBD status would be unlikely to influence the prenatal environment, we performed corresponding analyses of paternal IBD status as a negative control analysis.

Results
We identified 1,290,358 children born in Denmark between 1997 and 2022. Of these, 10,041 (0.8 %) had a mother with IBD before childbirth and 9,985 (0.8 %) had a mother with IBD onset after childbirth. Individuals were followed for a total of 18,370,420 person-years, with a median (IQR) follow up time of 14.4 (8.6, 19.9) years. A total of 3,537 individuals were diagnosed with IBD before the end of follow up. The hazard ratio of IBD in individuals born of mothers diagnosed with IBD before childbirth was 6.29 (95% CI 5.23, 7.56) compared to those whose mother did not have IBD. The corresponding hazard ratio for those diagnosed with IBD after childbirth was 3.88 (95% CI 3.27, 4.60) (p&lt;0.001). In our negative control analysis assessing risk based on paternal IBD status, risk was increased in the same direction. Hazard ratios of IBD were 5.26 (95% CI 4.22,6.56) and 3.73 (95% CI 3.10, 4.50) (p&lt;0.001), respectively (Figure 1).

Conclusion
In this population-based cohort study, the risk of IBD is highest among individuals with either parent diagnosed with IBD before childbirth. These findings suggest that the timing of parental IBD diagnosis, in addition to family history of IBD, influences IBD risk. Since these associations are consistent across maternal and paternal IBD status, genetic predisposition may play a weightier role than a prenatal inflammatory environment in the IBD risk of offspring to IBD patients.
P1122 Comorbidities Associated with Pediatric Onset Inflammatory Bowel Diseases: A Population-Based Study
Authors: Richard N , Leroyer A , Sarter H , Dupont C , Turck D , Bertrand V , Wils P , Gower-Rousseau C , Savoye G , Guillon N , Ley D , Fumery M 
Published: January 2024

Abstract

Background
Inflammatory bowel disease (IBD) can be associated with various disorders, including dermatological, rheumatological, or psychiatric conditions. However, little is known about the incidence of these co-morbidities in paediatric-onset IBD at the population-based level.

Methods
All patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) before the age of 17 between 1988 and 2011, and included in the EPIMAD population-based registry, were followed retrospectively until 2013. In this population, we collected information on comorbidities present at diagnosis, as well as events related to the development of a new chronic condition, hospitalization, or an infectious event of interest (as pneumopathy, meningitis, or pyelonephritis) reported in the medical records during the follow-up period.

Results
A total of 1,344 patients were included, comprising 1,007 (74.9%) with CD and 337 (25.1%) with UC. The median age at diagnosis was 14.3 years (IQR [11.7; 16.0]). During a median follow-up of 8.3 years ([4.3-13.9]), 361 (26.9%) patients exhibited at least one comorbidity. At diagnosis, 9.4% (95% CI [7.8% - 11.0%]) of patients had at least one comorbidity. The cumulative incidence of comorbidity was 13% (95% CI [11% - 14%]) at 1 year after diagnosis and 20% (95% CI [17% - 22%]) at 5 years. No association was found between the risk of comorbidity and the clinical characteristics at IBD diagnosis. However, the cumulative incidence of comorbidity was higher in the diagnosis period 2001-2011 than in the period 1988-1993 (HR=1.7 [1.2-2.2]; p&lt;0.001). The most frequent comorbidities were infectious (5.6%), dermatological (5.5%), and pulmonary (5.3%) (Figure 1). The most common infectious events included bacteraemia, digestive tract infection with Clostridioides difficile, and viral infection with Herpesviridae or parvovirus B19, with a cumulative incidence during follow-up of 1.2%, 1.0%, and 0.9%, respectively. During follow-up, viral infections with HBV, HCV, or HIV were observed in 0.2% of patients, and pneumopathy was diagnosed in 0.7% of patients. Eczema and asthma were the predominant dermatological and pulmonary comorbidities, affecting 2.6% and 5.1% of patients, respectively.

Conclusion
In this paediatric-onset IBD population-based cohort, the most common comorbidities were infectious, dermatological, and pulmonary. Bacteraemia emerged as the most prevalent severe infectious event during follow-up, affecting 1.2% of patients.