bluuebunny/crossref_metadata_2025 huggingface dataset:
P1013 Placebo rates in Crohn's disease: An individual patient data meta-analysis from multiple randomised controlled trials
Authors: Solitano V , Hogan M , Singh S , Danese S , Peyrin-Biroulet L , Zayadi A , Zou G , Sands B E , Feagan B G , Narula N , Ma C , Jairath V
Published: January 2024

Background

Estimating placebo rates and their determinants is essential for designing efficient randomised clinical trials (RCTs) in inflammatory bowel disease. We conducted an individual patient data (IPD) meta-analysis of placebo data from RCTs in Crohn’s disease (CD).

Methods

MEDLINE, Embase, and CENTRAL were searched from 01/2010 to 01/2020 for contemporary phase 2 and 3 placebo-controlled RCTs of biologics in moderate-to-severe CD. De-identified IPD from eligible trials that were available through the Vivli and Yale University Open Data Access data-sharing platforms were obtained. Primary outcomes were placebo clinical response and remission. Pooled placebo rates and 95% CIs were estimated using a 2-stage meta-analytical approach. Significant patient-level factors (P<0.05) associated with placebo rates were identified using regression analyses.

Results

Placebo IPD were available from 8 induction (n=1147) and 4 maintenance trials (n=524). Pooled placebo clinical response and remission rates varied based on outcome definition and prior biologic exposure (Figure). In induction trials, overall placebo response and remission rates were 27% (95% CI 23-32%) and 10% (95% CI 8-14%), respectively. Among bio-exposed patients, placebo response and remission rates were 27% (95% CI 16-40%) and 9% (95% CI 6-15%), respectively, compared with 29% (95% CI 24-34%) and 11% (95% CI 8-15%) for bio-naïve patients. Overall placebo response and remission rates in maintenance trials were 32% (95% CI 23%-42%) and 22% (95% CI 14-33%), respectively. Corresponding placebo response and remission rates for bio-exposed patients were 21% (95% CI 8-46%) and 17% (95% CI 11-25%), and 36% (95% CI 28-44%) and 24% (95% CI 15-36%) for bio-naïve patients. Placebo rates were lowest when response was defined as a ≥100-point decrease from baseline in the Crohn's Disease Activity Index (CDAI) score, and when remission was defined using stool frequency (≤1.5) and abdominal pain (≤1) subscores. Higher baseline C-reactive protein concentrations were associated with lower odds of placebo response and remission, while higher baseline albumin levels increased the odds of these outcomes (Table). Increased baseline CDAI and 2-item patient-reported outcome (PRO2) scores predicted higher odds of placebo response in induction trials, yet this reduced the odds of remission in induction trials and of both outcomes in maintenance trials. Prior failure to tumour necrosis factor (TNF) antagonist therapy was more predictive than prior TNF antagonist/biologic exposure for reducing the odds of placebo response and remission.

Conclusion

Placebo rates and the patient-level factors influencing them vary according to study design, clinical outcome measure and outcome definitions.
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

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

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 >500 patients which we categorised as very large volume. Despite variation in centre volume majority of respondents (75%) diagnose >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

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 >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

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

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

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 < 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

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<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<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

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<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.
P1136 Relationship between occupation and Inflammatory Bowel Disease’s activity in newly diagnosed patients
Authors: Mauriz Barreiro M V , Ruano-Raviña A , Ferreiro-Iglesias R , Baston-Rey I , Calvino-Suarez C , Nieto-Garcia L , Porto-Silva S , Martinez-Seara X , Dominguez-Munoz J E , Barreiro-de Acosta M
Published: January 2024

Background

It is well known that occupational activity can affect health. The association between type of work and Inflammatory Bowel Diseases (IBD) has been studied previously, but the studies on the topic are scarce and they do not have studied the relationship with clinical activity of the disease. The aim of this study is to elucidate if the type of work is a risk factor for the disease activity and severity in recently diagnosed IBD patients.

Methods

An observational prospective study including incident cases of patients with IBD diagnosed between June 2020 and September 2022 in the area of Santiago de Compostela was developed. Type of work, divided into white collar and blue-collar, sedentariness at work divided into high activity, moderate activity and sedentary activity according to the classification of occupational activity categories using accelerometry, and place of work divided into indoor and outdoor, time at work and contact with animals at work was recorded. All cases were followed-up through one year to assess the evolution of the disease. Endoscopic index at one year from the diagnosis, analytic parameters, hospitalizations related with the disease during the period, treatments administered, and number and severity of flares (measured by Partial Mayo Score and Harvey- Bradshaw) were collected. To analyze the results, a logistic regression was used.

Results

136 patients were included and followed their activity for a year. 68 (50%) were females. 78 (57.4%) had ulcerative colitis, 52 (38.2%) Crohn’s disease and 6 (4.4%) unclassified colitis. 30 patients (22.1%) had at least one flare during this time (23 had 1 flare, 5 two and 2 three), and 4 patients were primary non responders. 7 patients (5.2%) were hospitalized. Neither the type of job (white or blue collar), time at work (working hours per week), physical activity at work (sedentary work, moderate activity or high activity), working outdoor vs. indoor nor contact with animals at work were associated with hospitalization (all p>0.05). When contact with chemicals, solvents and dusts were analyzed, no statistically significant difference was found (p>0.05). Regarding the appearance of flares, high activity at work and working outside were protective factors of the appearance of a flare, with OR 0.1 (0.0 – 0.7) and 0.2 (0.1 – 0.8) respectively (Table 1).After stratifying results according to type of IBD, there were no statistically significant differences.

Conclusion

High activity jobs and working outside are protective factors for a flare appearance in patients with recent diagnosis of IBD. Type of job it is not related with risk of hospitalization.
P1145 Assessing disease control in inflammatory bowel disease (IBD) – a real world cross-sectional study in the UK
Authors: de Silva S , Steed H , Allen P B , Vegad C , Crooks J , Jaulim A , Hart A
Published: January 2024

Background

There is a paucity of data on disease control in patients with inflammatory bowel disease (IBD) in clinical practice. The Proportion Of suboptimal Disease Control And Strategy of Treatment in IBD (PODCAST-IBD) multicentre, non-interventional study aimed to quantify real-world rates of disease control using the STRIDE-II recommendations, explore contributors to, and the economic burden of, suboptimal disease control.

Methods

Cross sectional assessment of patients with IBD attending routine clinic appointments was carried out in four UK centres between Oct 2022 and Jan 2023. Clinician-reported outcomes, patient-reported outcomes and retrospective data from medical chart review were used to assess IBD control against red flags aligned to the STRIDE-II recommendations (Table). Health care resource utilisation (HCRU) was calculated using NHS reference costs.

Results

Data was available from 198 patients (Crohn's disease [CD]: 103, ulcerative colitis [UC]: 95) and most were currently receiving long-term IBD-specific treatment (CD: 85%, UC: 78%). IBD was suboptimally controlled in 52.4% (54/103) of patients with CD and 45.3% (49/95) with UC. Impaired quality of life (QOL), defined as Short inflammatory bowel disease questionnaire (SIBDQ) score <50, was the most frequent contributor to suboptimal disease control for both UC and CD. Other frequent contributors were systemic steroid overuse, extraintestinal manifestations (EIM), failure to achieve clinical improvement and perianal disease (Figure). Suboptimal disease control has a detrimental impact on fatigue and disability, demonstrated by lower (indicating more fatigue) mean total FACIT-F score in suboptimally controlled disease (CD: 81.5 vs 125, UC: 87.4 vs 122.8) and IBD Disk, a 10-item self-questionnaire used to assess IBD-related disability. HCRU more than doubled in patients with suboptimal vs optimal control (CD: £4,746 vs £1,924; UC: £2,428 vs £1,121), driven by more hospital admissions and emergency room visits in patients with suboptimal disease control. Patients with suboptimal disease control had higher rates of work productivity loss than those with optimal control (CD: 41.7% vs 11.9%, UC: 38.0% vs 22.6%).

Conclusion

This UK cross-sectional study found that IBD was suboptimally controlled in around one-half of patients based on STRIDE-II recommendations. Of those with suboptimally controlled disease one-third had impaired QOL making it the most common contributor. Suboptimal control of IBD had a considerable economic impact; HCRU more than doubled and productivity fell. Physicians could consider regular QOL assessments to prompt timely disease monitoring to enable identification of early active disease and ensure appropriate treatment.
P1180 Smoking behaviour and changes after diagnosis in patients with Crohn's disease in a tertiary referral hospital: A retrospective explorative study
Authors: Maurer J , Pokryszka J , Wisniowski K , Schreiner P , Primas C , Kazemi-Shirazi L , Dabsch S , Schweiger K C , Dejaco C , Neumann L , Reinisch W , Novacek G
Published: January 2024

Background

Smoking is the best-known environmental risk factor for poor outcome of Crohn’s disease (CD). Since smoking cessation improves the prognosis of CD, patients are encouraged to quit smoking. This study aimed to assess the smoking behaviour among CD patients and explore changes after diagnosis of CD.

Methods

This is a retrospective single tertiary center cohort study of 1267 patients with CD with a median follow-up of 16.8 years (IQR - 18.3) whose characteristics are recorded via a validated data software (IBDIS, Inflammatory Bowel Disease Information System). Smoking behaviour was categorized into never smokers, current smokers, and ex-smokers (those who quit smoking at any point). The primary objective was smoking cessation during follow-up. The probability of smoking was calculated for those CD patients who smoked at the time of diagnosis of CD by means of Kaplan-Meier estimates. Statistical analyses were conducted using R software, employing log-rank tests for estimating differences with a significance level of alpha = 0.05.

Results

In total 1,128 CD patients with a complete data set were analysed (Table 1). 161 (14.2%) patients started and stopped smoking prior to diagnosis of CD. At the time of diagnosis, 541 patients (47.9%) were smokers, and 239 (44.2%) of them quit smoking during follow up. The median time from CD diagnosis to cessation for the 239 patients who were smokers at the time of diagnosis and subsequently quit was 8.6 years (IQR - 10.6 years). 80 patients (7%) started smoking after diagnosis, with 50 of these patients quitting thereafter. The probability of smoking in those CD patients who smoked at the time of diagnosis decreased over time to 0.96 (95% CI 0.95-0.98) at 1yr, 0.85 (95% CI 0.83-0.89) at 5 yrs, 0.71 (95% CI 0.67-0.76) at 10 yrs, and 0.52 (95% CI 0.47-0.57) at 20 yrs after diagnosis for the entire cohort with no significant difference between genders (p=0.76) (Figure 1a). Patients who were diagnosed 2010 and later (n=182) were more likely to stop smoking than patients diagnosed before 2010 (n=359) (p<0.001) (Figure 1b). However, the probability to smoke 10 years after the diagnosis was still high in both groups (0.62 (95% CI 0.52-0.74) and 0.75 (95% CI 0.71-0.79), respectively).

Conclusion

A substantial proportion of CD patients smoked at the time of diagnosis. 20 years after diagnosis around half of the patients still continued to smoke. Improved smoking cessation programs are needed to reduce the impact of smoking on the course of the disease.
P1205 Features of the gut microbiota that associate with clinical outcomes of fecal microbiota transplantation in Ulcerative Colitis: a systematic review and meta-analysis
Authors: Benard M , de Goffau M , Blonk J , Hugenholtz F , van Buuren J , Paramsothy S , Kaakoush N , Borody T , Kamm M , Ponsioen C
Published: January 2024

Background

Evidence continues to accumulate highlighting the potential of fecal microbiota transplantation (FMT) to induce remission in patients with ulcerative colitis (UC). However, rational donor and recipient selection strategies and predictive biomarkers are needed to increase its efficacy. This systematic review provides a comprehensive evaluation of the current literature on microbial factors of FMT donors and UC recipients that relate to clinical outcomes.

Methods

The MEDLINE, Embase and Cochrane databases were systematically searched through April 2023 for relevant studies. The quality of studies and risk of bias was analyzed with Joanna Briggs tools and a compound critical appraisal-score. Additionally, species-level data from two randomized controlled trials (TURN and FOCUS) were re-analyzed from a compositional perspective.

Results

Out of 2983 citations identified, 47 met the inclusion criteria, of which 20 fulfilled quality appraisal. Higher clinical response rates were associated with higher bacterial alpha-diversity of stools of UC recipients at baseline and following FMT, and with higher FMT donor alpha-diversity. Engraftment of the donors’ microbiota was often reported but could not be clearly linked to clinical response, possibly because not every donor has an ideal microbiome. Taxa most frequently reported to be related to response included members of the Lachnospiraceae family (e.g., Eubacterium rectale, Blautia obeum) and Oscillospiraceae family (e.g., Faecalibacterium prausnitzii, Ruminococcus bromii) whereas members of the Proteobacteria and Fusobacteria phyla and Ruminococcus gnavus were reported to correlate to non-response. Low virome richness and low Caudovirales bacteriophages at baseline as well as a decrease of Candida levels following FMT, were associated with clinical response. Compositional analyses showed that a clinical response is associated with a shift away from a low diversity, Bacteroides2-enterotype-like composition towards one of high diversity either dominated by various butyrate producers, the Christensenellaceae-Methanobrevibacter trophic network or a high diversity composition with abundant but not excessive levels of Prevotella copri.

Conclusion

In this systematic review we found distinctive features of microbial profiles of both donors and UC recipients to relate to clinical response to FMT. The predictive value of microbial markers should be further explored in future clinical studies to move towards a personalized FMT approach and delineate ‘super-donor’ profiles.
P1214 The crosstalk between oral and intestinal microbiota in inflammatory bowel disease patients
Authors: Xiang B , Runzhi C , Min Z , Yuanqi Z , Xiang P , Wei W , Qi Z , Zhiyin G , Jun H , Tao D , Min Z
Published: January 2024

Background

Background: Previous studies reported that oral microbes can migrate to the gut, but the relationship between oral and intestinal microbiota in inflammatory bowel disease (IBD) is still unclear.

Methods

Here, we investigated the oral and gut microbiota of patients with Crohn’s disease (CD) and ulcerative colitis (UC), as well as their healthy relatives. We combined second- and third-generation sequencing based on the 16S rRNA gene to analyze the oral and fecal microbiota.

Results

A total of 97 IBD patients (59 CD and 38 UC) and 94 healthy relatives were included in the study. Our finding showed that CD and UC patients had higher levels of pathogenic bacteria in both their oral and fecal microbiota. In IBD patients, the gut microbiome was more influenced by the oral microbiome compared to healthy relatives, particularly in CD. We also observed an interesting interaction between Veillonella and Escherichia-Shigella in CD, and the presence of Veillonella in the gut was associated with disease activity. We developed diagnostic models that combined oral and fecal genera, which effectively distinguished CD (AUC=0.8478) and UC (AUC=0.7826) from healthy relatives, as well as predicted active inflammation in CD (AUC=0.9226) and UC (AUC=0.9158). Additionally, our third-generation sequencing results revealed an increase in Parvimonas micra in the oral cavity of IBD patients, and this was positively correlated with its presence in the feces.

Conclusion

These findings suggest that both oral and gut microbiota may play a crucial role in the development of IBD and could be potential targets for intervention.
P1226 Determination of oral and gut mucosal microbiome profiles of patients with treatment-naïve ulcerative colitis
Authors: Karakan T , Özmeriç Kurtuluş N , Ünsal B , Çağrı İşler S , Akça G , Soysal F , Cindoruk M , Elgün Ulkar S , Açık L , Ergin M , Abbasov Z , Özkul Koçak C , Ekmen N , Yalınay A M , Özkan S , Karataş A , Paes Batista Da Silva A
Published: January 2024

Background

The oral microbiome in ulcerative colitis (UC) patients and its role in the pathogenesis of the disease are still poorly understood. Although there are studies investigating the composition of oral microbiome in UC, there are no studies on concomitant analyses of oral and colonic mucosal samples in treatment-naïve patients. In this study, the oral and mucosal gut microbiome of UC patients and oral microbiota of healthy individuals (HC) were compared.

Methods

Sixty patients with newly-diagnosed active (mild-moderate severity) UC patients (n=30) and HC (n=30) were included in the study. Dietary habits were stable in the last three months of participants (checked by dietary recall questionnaires) and co-morbidities affecting microbiota profiles were excluded. Multiple colonic mucosa biopsies were obtained from inflamed areas before treatment in UC group. Simultaneously, subgingival plaque samples were analyzed. All samples were identified through next-generation DNA sequencing analysis, evaluated using bioinformatic tests.

Results

The potential signature bacterial species associated with UC were determined by examining of both gut and oral microbiomes. According to the Microbiome Lefse analysis, Prevotella copri emerged as the prominent common species in the colonic mucosal and subgingival plaque biopsies of UC group. Oral microbiome comparison between UC and HC patients revealed increased Haemophilus parainfluenza and Corynebacterium durum species and decreased F. prastnutzii and Akkermansia muciniphilia in the UC group (p<0.022). Comparative Boxplot analysis of bacterial abundance and alpha-diversity, as indicated by the Shannon index data, revealed that the HC group exhibited higher bacterial abundance and diversity in subgingival plaque samples than the UC group. We found significant association of Bacteroides vulgatus, Prevotella copri, Bacteroides fragilis, Parabacteroides merdae in both colonic mucosal and subgingival plaque samples (oral microbiome) of UC patients (p<0.044).

Conclusion

Our study is the first to show the oral and colonic mucosal microbiome relationship in UC. The presence of oral dysbiosis associated with UC in our study supports the hypothesis that UC could be associated not only with gut dysbiosis, as previously observed, but also with an imbalance in the oral microbial communities. Interestingly, we could not detect previously reported species of Streptococcus, Oribacterium, Rothia, Neisseria and Porphyromonas in the oral microbiome samples of the UC group. However, oral and gut microbiome profiles share some common microorganisms such as Prevotella copri and Bacteroides fragilis. Further studies are required for determining the potential role of oral dysbiosis is disease severity.
P1227 Revealing lower capacity of microbial metabolism of flavonoids and associated metabolic changes in Crohn’s disease
Authors: Xiang L , Zhuo S , Luo W , Tian C , Feng R , Zhu Y , Chen M
Published: January 2024

Background

Recent studies highlight the role of interplay between oxidative stress, gut microbiota, and immune response in the etiology of Crohn’s disease (CD). Polyphenols are natural antioxidants which are mainly metabolized by gut microbiota and could modulate the composition of gut microbiota. However, it’s yet reported whether there is difference in polyphenol-degradation capacity of gut microbiota in CD and healthy controls (HCs).

Methods

A comprehensive literature search was conducted on microbial metabolic pathway of polyphenols and the responsible organisms and genes were recorded. The polyphenol-degrading genes were quantified using shortBRED in three clinical cohorts (the First Affiliated Hospital of Sun Yat-sen University (FAH) cohort, PRISM cohort, and HMP2 cohort). Microbiota abundance was analyzed in FAH and PRISM cohort. Polyphenol intake and serum metabolites were assessed in the FAH cohort. Enterotype analysis was performed in FAH cohort. Correlation analysis among polyphenol intake, gene abundance, serum metabolites and bacterial abundance was conducted.

Results

Phylogenetic tree revealed that reported polyphenol-degrading bacteria were mainly distributed to Actinobacteria and Firmicutes. The abundance of flavonoid degradation related genes (mainly flavone reductase, chalcone isomerase and phloretin hydrolase) was significantly decreased in patients with CD in FAH cohort, but not in PRISM and HMP cohort. Difference in abundance of polyphenol-degrading bacteria was observed between CD patients and HCs in FAH and PRISM cohort. In addition, lower polyphenols intake and serum hippuric acid (HA) level were detected in CD patients. Enterotype analysis revealed that CD patients were mainly distributed to Enterobacteriaceae- and Bacteroidaceae-dominated enterotype while HCs were mainly distributed to Ruminococcaceae- and Prevotellaceae-dominated enterotype. Serum HA level was higher in healthier enterotypes (Ruminococcaceae and Prevotellaceae dominant) and positively correlated with flavonoid-degrading organisms and butyric acid-producing organisms. No positive correlation between abundance of polyphenol-degradation genes and polyphenols intake was detected.

Conclusion

The current study summarized the polyphenol metabolic pathway mediated by gut microbiota and quantified genes responsible for polyphenol degradation. Our comprehensive analysis of diet-microbiota-gene-metabolite data revealed a lower capability of flavonoid degradation in gut microbiota and lower HA level in CD patients. Finally, our findings provide a foundation for future work exploring the polyphenol or polyphenol-degrading microbiota interventions in preclinical models of CD.