bluuebunny/crossref_metadata_2025 huggingface dataset:
P803 Plasma N-glycan biomarkers predict patient Response to Vedolizumab treatment for Crohn’s Disease
Authors: Elgood Hunt G , Adams A , Senard T , Gardner R , Jonge W , Li Yim A , Noble A , Satsangi J , Joustra V , D’Haens G , Spencer D
Published: January 2023

Background

Vedolizumab (VDZ) is a monoclonal antibody directed against α4β7 integrin used to treat Crohn’s disease, which has proven to be efficacious in phase 3 clinical trials¹ and in real-world studies². However, there is a need for reliable biomarkers to predict whether an individual patient will respond to VDZ treatment. Glycosylation changes have been associated with CD, but have never been studied as potential predictors of remission to biological therapy³. A comparison of plasma N-glycan profiles between responders and non-responders to VDZ was used to detect potential biomarkers to response.

Methods

Plasma samples before (t1) and after (t2) initiation of vedolizumab treatment (mean follow up time at t2 215 ± 61 days) were taken from 58 patients with Crohn’s disease. They were analysed by high-performance liquid chromatography with mass spectrometry. Response to VDZ was assessed by a combination of clinical and endoscopic outcomes and was observed in 34 of 58 patients. 89 direct glycan traits met the criteria for quantification and were extracted from the data via LacyTools. Consequently, 21 derived glycan traits were calculated by combining direct traits with shared structural similarities. Correcting for age and sex, the direct and derived traits were tested across responses using logistic regression and cross-validation to determine which traits at t1 are predictive of response (p-value < 0.05) and traits at t2 are markers of response (p-value < 0.05).

Results

Two glycans, MAN6 (0.65 AUC) and FA2G2S2 (0.7 AUC) were higher in responders prior to treatment and moderate predictors of response, with no improvement in a combined model (figure 1A). Congruent to previous studies, galactosylation levels increased in responders after treatment. Overall, 17 direct traits and 4 derived traits were markers of response after treatment and collectively proved to be good predictors of response (0.80 AUC) (figure 1B).

Conclusion

This study has demonstrated multiple N-glycans are indicators of future response to VDZ treatment, with the potential to guide clinicians in determining the most appropriate form of treatment for individuals. These data require to be validated in the future; and to be assessed alongside other emerging biomarkers.

References:

1 Sands BE, et al .2014 Sep;147(3):618-627.e3

2 Bressler B,et al.2021 Mar 30;15(10):1694–706.

3 Šimurina M, et al. 2018 Apr;154(5):1320-1333.e10
P814 Clinical trial design in Crohn’s disease: interpreting future endpoints based on post hoc analyses of the vedolizumab phase 3 trials GEMINI 2 and VISIBLE 2
Authors: Khan R M Q , Schwartz D A , Sands B E , Hanauer S , Uddin S , Mukherjee R , Lichtenstein G
Published: January 2023

Background

Crohn’s disease (CD) is a chronic, relapsing–remitting disease characterized by inflammation of the gastrointestinal tract. Historically, the Crohn’s Disease Activity Index (CDAI) has been used to assess outcomes in clinical trials involving patients with CD. However, in contrast to the alignment of regulatory standards for trials in ulcerative colitis, the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) differ regarding the most appropriate endpoint definitions for trials in CD. We examined how clinical remission endpoints in CD trials have evolved and conducted post hoc analyses of two vedolizumab trials, GEMINI 2 and VISIBLE 2, to understand how endpoint definitions influence clinical trial outcome measures of treatment efficacy.

Methods

Endpoint definitions of clinical remission in completed and ongoing phase 3 trials of advanced therapies in CD were extracted from published literature and ClinicalTrials.gov. Post hoc analyses of data from GEMINI 2 and VISIBLE 2 were conducted by measuring the difference (%Δ) between the proportions of patients achieving clinical remission with vedolizumab versus placebo at week 52 as assessed by six endpoint definitions (A: stool frequency score [SFS] ≤ 2.8 and not worse than baseline score; B: SFS ≤ 3 and not worse than baseline score; C: abdominal pain score (APS) ≤ 1 and not worse than baseline score; D: SFS ≤ 2.8 and APS ≤ 1; E: SFS ≤ 3 and APS ≤ 1; F: CDAI ≤ 150) (Figure 1).

Results

Most phase 3 trials of advanced therapies in CD included a clinical remission endpoint that was defined by CDAI score: typically, CDAI < 150 or ≤ 150. However, several recent trials have also included a primary or secondary clinical remission endpoint defined using components of the CDAI score such as SFS and APS (Table 1). Post hoc analyses of GEMINI 2 and VISIBLE 2 revealed minimal change in %Δ for each of the new endpoint definitions tested compared with the primary analysis for each trial (Figure 1).

Conclusion

Objective measures, including patient-reported outcomes and components of the CDAI score such as SFS and APS, have been used to define clinical remission in recent CD trials. Despite differences in regulatory guidance for defining clinical remission, our post hoc analyses of GEMINI 2 and VISIBLE 2 reveal that the efficacy of vedolizumab, measured using a variety of endpoint definitions from recent CD trials, was similar to that previously reported using CDAI ≤ 150.
P818 Survival of ustekinumab treatment based on concomitant immunomodulator use
Authors: García Ramírez L , Suárez Ferrer C , Rueda Garcia J L , Martín-Arranz E , Poza Cordón J , Sánchez-Azofra M , Martin-Arranz M D
Published: January 2023

Background

Given the low immunogenicity of ustekinumab (UST), it has been suggested that it is not necessary to add an immunomodulator (IMM). However, there is little scientific evidence on whether the efficacy of combined UST+IMM treatment may be greater than in monotherapy, due to the concomitant action of both drugs. The aim of the study was to evaluate the survival of UST treatment with and without concomitant IMM.

Methods

Patients with stable follow-up at Hospital Universitario La Paz (Madrid), with Crohn’s disease (CD) and previous or current treatment with UST, since May 2016, were retrospectively included.

Results

A total of 137 patients were included. Table 1 shows the baseline characteristics.

In 98 patients (71.53%) UST indication was induction of remission; in 22 (16.06%) post-surgical recurrence treatment; in 5 (3.65%) it was prescribed as post-surgical recurrence prophylaxis; and in the remaining 12 (8.76%) the indication was for other reasons.

At the time of analysis, 91 (66.42%) patients were still on active treatment and 46 (33.58%) had discontinued treatment (of which 9 due to primary failure, 27 due to secondary loss of response, 9 due to adverse events, 1 due to remission).

89 patients (64.96%) did not receive concomitant IMM. Whilst, 48 (35.04%) received concomitant treatment with an IMM. The mean time of IMM treatment was 9.16 years (SD 6.76).

UST treatment had a mean duration of 2.19 years (SD 1.35) in patients receiving concomitant IMM; while it was of 1.67 years (SD 1.02) in those who did not receive concomitant IMM; being this statistically significant (p=0.0124) (Figure 1).

When performing a multivariate analysis by linear regression, the only variables that negatively influenced UST survival were age at diagnosis (Coef. -0.36; p=0.028), perianal disease (Coef. -0.29; p=0.198) and location rather than L1 (Coef. 0.2; p=0.072). However, concomitant IMM use had a positive influence (Coef. 0.45; p=0.032).

Conclusion

In our experience, the survival of ustekinumab is greater in combined treatment with immunosuppressant, being also the only independent variable associated with a greater durability of the drug.
P821 Improving outcome after Inflammatory Bowel Disease surgery in an Enhanced Recovery After Surgery setting
Authors: Juvik A F , Poulsen J K , Roikjaer O , Fransgaard T
Published: January 2023

Background

Enhanced Recovery After Surgery (ERAS) has been known to improve patient outcome after colorectal cancer surgery. However, far less data exists on ERAS used in patients undergoing surgery for Inflammatory Bowel Disease (IBD).

Methods

From March 2020 our surgical IBD patients were admitted to a dedicated colorectal ward instead of a general surgery ward. The colorectal unit already had a history of ERAS for colorectal cancer patient and has specialized ERAS-nurses. The goal was also that IBD-surgery preferably was done by two surgeons from the colorectal team.

Data on all elective IBD surgery in our department from January 2018 through June 2022 was collected from our local IBD-surgery database in order to compare Length of Stay (LOS), readmission rates, surgical approach and complication rates before and after March 2020.

Results

In total 233 patients underwent resections on small bowel, colon or rectum in our institution in a 4.5 year period. Patients undergoing emergency surgery were excluded. In the first period until March 2020, 105 patients were operated and in the second period until June 2022, 128 patients went to surgery. The demographic data (Table 1) show two comparable groups as it does for type of surgery (Table 2).

The median LOS decreased from 6 to 4 days over time and the readmission rate was not significantly changed in the same period. Laparoscopic surgery was done on a larger percentage of the patients in the later period and the conversion-rate was significantly decreased in the same period. There was no difference in surgical complication rate (Table 3).

Conclusion

Admitting IBD patients undergoing surgery to a dedicated unit with specialized surgeons and nurses in an ERAS setting can reduce LOS and improve the surgical technique.
P829 The Burden of Colorectal Cancer in Patients with Ulcerative Colitis – Incidence and Risk factors from a Population-based Inception Cohort from Veszprem county, Western Hungary, from 1977–2020
Authors: Wetwittayakhlang P , Golovics P , Gonczi L , Khoury A , Kurti Z , Pandur T , David G , Erdelyi Z , Szita I , Lakatos L , Lakatos P L
Published: January 2023

Background

Limited data are available on the incidence and risk of colorectal cancer (CRC) in ulcerative colitis (UC) from population-based studies in Eastern Europe. We aimed to identify the long-term incidence trends and predictors of CRC in a prospective population-based inception cohort from Veszprem, Western Hungary.

Methods

Patient inclusion for the inception cohort was between January 1,1977 and December 31,2018, and follow-up ended December 31,2020. The risk of CRC was estimated using standardized incidence ratios (SIRs). Age-and gender-specific CRC rates of the background population were derived from the National Cancer Registry.

Results

A total of 1,370 incident UC patients were included [male:51.2%, median age at diagnosis:37years). During a median follow-up of 17 years(IQR9-24), CRC was diagnosed in 41 UC patients(2.99%), equaling 1.76/1000 person-year(py).Median age at CRC diagnosis was 59(IQR:50.0-67.5) years. Overall SIR of CRC was 2.02(CI95%:10.1-12.1). SIRs were higher in extensive colitis (SIR:3.77, CI95%:2.41-5.91). The cumulative probability of CRC at 10-,20 and 30 years was 0.9% (95%CI0.6-1.2), 3.5%(95%CI2.8-4.2), and 6.5%(95%CI5.4-7.6), and there was no difference in the risk of CRC over different decades of UC diagnosis in a Kaplan Meier analysis(Log-rank=0.693). In multivariate analyses, co-existing PSC(HR4.19;95%CI1.72-10.20), colonic dysplasia(3.42;95%CI1.04-11.26), and extensive colitis (HR2.15;95%CI1.29-3.60) were identified as a significant predictor for CRC.

Conclusion

We report an increased CRC risk in UC patients with a standardized incidence ratio of approximately 2 folds, with a stable CRC risk over four decades. Disease extent, co-existing PSC and dysplasia were identified as predictors of CRC.
P846 Epidemiological and Clinical Characteristics of Inflammatory Bowel Diseases in Patients from Greece
Authors: Liava C , Sinakos E , Dimitroulas T , Navrozidou C , Akriviadis E
Published: January 2023

Background

There are few reports from Greece about the epidemiological and clinical features of inflammatory bowel diseases (IBD), which were mainly evaluated in retrospective studies with data collection from hospital registries. We aimed to determine the epidemiological profile and clinical features as well as to detect any differences between patients with Crohn’s disease (CD) and ulcerative colitis (UC), based on retrospectively-prospectively collected data from a cohort of IBD patients followed in daily clinical practice.

Methods

Patients with biopsy-confirmed IBD aged 10–90 years old were included in the study. A comprehensive questionnaire was used to collect data on each site visit from July 2018 until March 2022. Logistic regression analysis and chi-squared test were used to compare the frequency of epidemiological and clinical characteristics between patients with UC and CD.

Results

We collected 300 patients diagnosed with IBD (180 with CD, 113 with UC, and 7 with indeterminate colitis). The median age of IBD patients was 42 years. The onset of disease in CD group was observed between 17 and 40 years of age in the majority of patients (58%). Ileocolonic location of CD was present in 70% of CD patients; 39% had stricturing behavior and 29% had perianal disease (abscesses and fistulas). CD patients developed more often aphthous stomatitis (34%) than patients with UC (13%, OR 3.45; 95% CI: 1.76-6.78; P< .001). Patients with CD had a 20-fold increased risk to undergo a surgical procedure (OR 19.87; 95% CI: 6.03-65.48; P< .001), mainly enterectomy (26%), as shown in table 1. At study entry, C-reactive protein (CRP) elevation was more frequently present in CD compared to UC patients (OR 1.93; 95% CI: 1.04-3.59; P< .05). Most patients with UC had extensive colitis (56%). Mesalamine was predominantly used in UC patients (81% vs 46% in CD, P< .005), and sulfasalazine and thiopurines in CD patients (60-70% vs 9-13% in UC, P< .005), as shown in table 2. The most commonly used anti-TNF agent was Infliximab, mainly in CD patients (24% vs 4% in UC, OR 0.12; 95% CI: 0.04-0.34; P< .001). Adalimumab was used in 12% of IBD patients and Vedolizumab in 8%. Around 4% of patients with complicated CD received Ustekinumab. Tofacitinib was used in 2% of patients with severe complicated UC and extraintestinal manifestations. Enteral diet (Modulen®) was used in 6% of CD patients and in only 2% of UC patients with severe UC pancolitis.

Conclusion

In this retrospective-prospective cohort study of 300 patients with IBD, CD patients had a significantly higher risk of developing aphthous stomatitis and increased levels of CRP. CD patients also required more often treatment with anti-TNF agents and immunosuppressants, and a surgical procedure, mainly enterectomy.
P849 Exposure to metals and minerals in hair samples of patients with preclinical inflammatory bowel disease
Authors: Rodríguez-Lago I , Rodríguez A , Elorza A , Sampedro B , Jiménez I , Erdozáin I , Rodríguez P , Fraga A , De Castro L , Oyón D , Huerta A , Carmona M , Esáin A , Cabriada J L , Barreiro-de Acosta M
Published: January 2023

Background

Previous data have shown that the inflammatory process underlying ulcerative colitis (UC) and Crohn’s disease (CD) can start years before the diagnosis, but the role of triggering factors and environmental exposures is still unknown. Hair element analysis is a valuable and inexpensive screen for physiological excess or deficiency of certain elements. Our aim was to determine if patients with an incidental diagnosis of UC or CD demonstrate exposure of minerals or toxic metals in the years preceding the symptomatic onset of the disease.

Methods

We performed a prospective single-center study including all asymptomatic subjects with a diagnosis of UC or CD during the colorectal cancer screening program between January 2021 – June 2022 in Vizcaya (Basque Country, Spain). The diagnosis of IBD was established by a combination of clinical data, endoscopic findings suggestive of UC or CD, and after histologic confirmation. Cases were compared with a healthy non-IBD control population. An approximate hair sample of 0.25 g was obtained up to 3 months since diagnosis. We used a commercial kit that allows the investigation of 17 metals (Al, Sb, As, Ba, Be, Bi, Cd, Pb, Hg, Pt, Tl, Th, U, Ni, Ag, Sn, Ti) and 22 minerals (Ca, Mg, Na, K, Cu, Zn, Mn, Cr, V, Mo, B, I, Li, P, Se, Sr, S, Co, Fe, Ge, Rb, Zr). Descriptive statistics and non-parametric tests were used for comparisons between both groups.

Results

Three patients with preclinical IBD were included (median age 53 years; 67% male; all former smokers). Two of them had a diagnosis of UC (one left-sided colitis and one extensive colitis) and one with ileal CD. Extraintestinal manifestations were observed in one patient (33%). No family history of IBD was reported. Thirteen healthy controls with no relevant environmental exposures (median age 34 years; 69% female; 92% non-smokers). We found that cases demonstrated statistically significant higher concentrations of bismuth, sodium and boron compared to controls (Figure). In contrast, there was a lower exposure to uranium, zinc and germanium, with a trend towards lower copper levels among cases.

Conclusion

A range of environmental exposures can be identified during the preclinical phase of IBD. However, their relationship with the symptomatic onset and disease progression should be further explored.
P867 Cost-effectiveness and cost-only studies for Inflammatory Bowel Disease surgery: a scoping review
Authors: Leeds I , Prien C , Dill-Macky A , Li H , Lincango E , Holubar S
Published: January 2023

Background

Studies examining the relative cost-effectiveness of surgical procedures and surgery-related interventions for patients with inflammatory bowel disease (IBD) remain limited. This dearth of studies hampers decision-makers’ assessment of surgery-related interventions for IBD patients. The purpose of this study was to conduct a scoping review of available literature for cost-effectiveness analyses of IBD-related surgery.

Methods

We performed a comprehensive search of English-language articles in MEDLINE, EMBASE, Cochrane Reviews, and Scopus from each database's inception to May 1, 2022. Preplanned controlled vocabulary related to IBD and its subtypes, surgery, and measures of costs were used. We defined study selection criteria to include all IBD-related surgical interventions (including preoperative, intraoperative, and postoperative) in all age groups that also reported a measure of costs of care. Studies comparing medical versus surgical interventions for refractory IBD were excluded. All search findings were screened by two reviewers using titles, abstracts, and ultimately full-length manuscripts. Full screened studies were then extracted for study characteristics and findings to facilitate a qualitative synthesis of results.

Results

We identified 1,804 citations for screening and ultimately found 10 formal cost-effectiveness studies and 56 cost-only studies. Cost-effectiveness studies assessed intraoperative (50%) and postoperative interventions (50%) mostly in patients with Crohn's disease (60%). Topics included comparisons of surgical approach (50%), venous thromboembolism prophylaxis (30%), and surveillance for postoperative recurrence (2%). Of the cost-only studies, the majority focused on intraoperative interventions (89%), particularly in ulcerative colitis patients (60%). Areas of interest included costs associated with healthcare resource utilization during a surgery-related admission (89%), venous thromboembolism prophylaxis (4%), and others (7%). Pre-defined areas of interest with no reported interventions included IBD-specific roles of Enhanced Recovery After Surgery interventions such as alvimopan, robotic surgery, timing to surgery, surgical therapies for perianal disease, pediatric Crohn's Disease, and genetic testing.

Conclusion

A scoping review found minimal literature using cost-effectiveness techniques to inform IBD-related surgical care. There are many more cost-only than cost-effectiveness studies related to these clinical topics. This asymmetry highlights immediately available opportunities for broadening the use of cost-effectiveness analysis of IBD-related surgical interventions.
P868 Clinical features of chronic enteropathy associated with SLCO2A1 gene
Authors: Umeno J , Fuyuno Y , Torisu T , Matsuno Y , Esaki M , Yanai S , Ohmiya N , Hisamatsu T , Watanabe K , Hosoe N , Ogata H , Hirai F , Hisabe T , Matsui T , Kitazono T , Matsumoto T ,   CEAS study group
Published: January 2023

Background

Chronic enteropathy associated with the SLCO2A1 gene (CEAS) is a hereditary disease caused by mutations of the SLCO2A1 gene which encodes a prostaglandin transporter. This disease is rare and intractable characterized by persistent blood and protein loss. There are few reports from Europe, and most reports are from Asian countries such as South Korea, China, and Japan. Because CEAS and Crohn's disease (CD) present ileal ulcers and stenoses, it is often difficult to distinguish CEAS from CD. Evaluation of characteristic upper gastrointestinal lesions observed in CEAS and extraintestinal findings, such as digital clubbing, periostosis, and pachydermia, can trigger suspicion of this disease, and genetic testing can be performed to confirm the diagnosis. Since little is known about the clinical features of CEAS, we conducted a nationwide survey in Japan.

Methods

All study participants provided written informed consent for genetic analysis. The present study was approved by the ethics committee of each institution. During the period between 2012 and 2022, 188 patients suspected of CEAS were enrolled in this study and checked to have SLCO2A1 gene mutations. We reviewed the clinical information of genetically confirmed CEAS patients.

Results

We confirmed the genetic analysis of 69 CEAS patients (24 males and 45 females) and found 19 different types of SLCO2A1 mutations. The median age at disease onset and diagnosis was 19 (range 1-69) and 42 (range 7-70) years, respectively. Parental consanguinity was present in 19 patients (26%). Although anaemia was present in almost all patients, only two patients experienced gross haematochezia. The median haemoglobin and serum total protein levels at diagnosis were 9.7 (range 2.3-14.4) and 5.3 (2.7-8.2) g/dl, respectively. Thirty-seven patients (54%) had undergone intestinal surgery. The most frequently involved gastrointestinal site was the ileum (94%), but the terminal ileum was rarely involved (4%). The lesions were shallow ulcers, varying in shape from circular, oblique, to longitudinal, sometimes forming pseudodiverticulum or luminal stenosis. The Gastric lesions were observed in 15 patients (22%) and duodenal lesions in 30 patients (43%). 20 patients (30%) had either mild digital clubbing, periostosis, or pachydermia. The extraintestinal findings, were more frequently found in males than in females (digital clubbing 52% vs 9%; periostosis 50% vs 10%; pachydermia 57% vs 0%).

Conclusion

Examination of the clinical features of CEAS reveals that ileal lesions are uniform and characteristic, but clinical features are diverse. Thirty per cent of patients with CEAS have extraintestinal features. There is a significant gender difference in extraintestinal features in CEAS patients.
P870 What had the greatest impact on the quality of life of IBD patients on intravenous biological therapy in Montenegro during COVID-19?
Authors: Smolovic B , Lukic M , Djurovic M , Muhovic D , Bojovic S
Published: January 2023

Background

COVID-19 has affected the quality of life (QoL) of patients with chronic diseases, including patients with IBD. The aim of this study is to evaluate the QoL of patients with IBD on intravenous biological therapy (IvBT), through the Short Inflammatory Bowel Disease Questionnaire (sIBDQ), and to correlate the results with sociodemographic data of the patients.

Methods

This study was comprised of patients older than 18 years of age, with a pathohistologically confirmed diagnosis of IBD (Ulcerative Colitis (UC), and Crohn’s Disease (CD)). The study was conducted on September and October 2020, during one of the highest incidences period of COVID-19 in our country. Patients completed the sIBDQ, and DASS-21 (Depression, Anxiety and Stress Score-21) questionnaire too, assessing their level of depression, anxiety and stress. For significant symptoms (DASS-21), we used at least moderate DASS-21 subscale score: DASS-21 Depression (≥ 14), DASS-21 Anxiety (≥ 10) and DASS-21 Stress (≥19). The Simple Clinical Colitis Activity Index was used to assess the disease activity of UC; for CD, the Harvey-Bradshaw Index was used. Patients who scored below 50 on the sIBDQ were those labeled with worse QoL. We also examined demographic data, data on IBD characteristics and COVID-19 data and their impact on quality of life.

Results

Of the total number of patients (94), there were 40 (42.5%) females, 42 (44.6%) with CD. All patients have been receiving IvBTh (anti TNFα: infliximab-originator and biosimilar (59 patients) and anti-integrins: vedolizumab (35 patients)) for at least 6 months prior. The results indicated worse QoL in 25 (27%) patients. Multivariate analysis showed that the greatest impact on poor QoL during the COVD-19 pandemic were: active disease (p= 0.002), significant symptoms on the DASS21 score (p= 0.013), patients who did not regularly go to work or were not employed (p=0.017), if they had a patient with COVID-19 in their immediate environment (p=0.024) and those who had a higher degree of health concerns about coming to regular admission to biological therapy at the IBD unit. (p=0.046).

Conclusion

27% of IBD patients on IvBT had worse QoL during the COVID 19 pandemic. In addition to disease activity and significant psychological disturbances, other reasons for lower QoL were identified during the pandemic and are directly related to it.
P881 Is occupation a risk factor for developing Inflammatory Bowel Disease? A case-control study
Authors: Mauriz Barreiro M V , Ruano-Ravina A , Ferreiro-Iglesias R , Baston-Rey I , Porto-Silva S , Nieto-Garcia L , Martinez-Seara X , Martin-Gisbert L , Dominguez-Munoz J E , Barreiro-de Acosta M
Published: January 2023

Background

The role of occupation is well established for different diseases. Nevertheless, there is a lack of information on the role of occupation on the onset of inflammatory bowel diseases. Many occupations entail the exposure of different toxic substances that may reach the bowel through different biological pathways (bloodstream or digestive tract) and act as possible triggers of such diseases, mainly Crohn′s disease and ulcerative colitis. The aim of this study is to identify if there is a role of occupation on the onset of IBD using a case-control study.

Methods

A prospective case-control, single-center study was designed. All Incident cases with any of the main IBD diseases (ulcerative colitis, Crohn’s disease and unclassified colitis) were consecutively included. Controls were patients selected from the consults and endoscopic room of the Digestive Unit of Clinical Hospital of Santiago de Compostela without any autoimmune chronic disease. Cases are patients with IBD disease diagnosed 3 or less months prior to the inclusion and over 18 years old. Cases and controls were recruited simultaneously and controls followed a sex and age frequency matching with cases. All participants were recruited from June 2020 to September 2022. A detailed questionnaire describing the occupations held and time of them was used. Blue-collar jobs have been defined as those entailing the highest risk occupational exposures and are also mentioned as manual workers. White-collar jobs are usually those with more office-related work, but also with teaching or health sector. To analyze the results, we used a logistic regression. A subgroup analysis was performed by each of the three diseases considered.

Results

129 patients with incident IBD (73 with ulcerative colitis, 51 with Crohn’s disease and 5 with indeterminate colitis) and 114 controls were included. Comparing patients with IBD with controls, there were no statistically significant differences between type of work, working hours, contact with animals or physical activity at work. Among the patients with IBD, there were no differences in the number of flares between groups (blue collar workers vs. white collar (p>0.05), outside workers vs. indoor ones (p>0.05), sedentariness vs. moderate activity or high activity (p>0.05) or animal contact vs. no contact (p>0.05)). Taking into account only patients with current work activity, the results did not change. After stratifying results according to type of IBD, there were no statistically significant differences either (table 1).

Conclusion

In this study, differences between type of work, working hours, contact with animals or sedentariness were not associated with the risk of IBD nor with the activity of this disease.
P900 Studying causality association of ustekinumab with cardiovascular disease outcomes using Mendelian randomization
Authors: Miguel González J A , Sánchez Mayor M , Cervera Seco L M , Gaite Reguero A , Pavlidis P , Martínez Marigorta U
Published: January 2023

Background

The human antibody ustekinumab targets the common p40 subunit between both pro-inflammatory interleukin-12 (IL-12) and interleukin-23 (IL-23) that upregulate T cell differentiation towards T helper 1 (TH1) and T helper 17 (TH17) respectively. The blockade of the IL12-IL23 pathway has been shown to be an effective therapeutic option for Inflammatory Bowel Disease treatment, however a recent epidemiological study has reported a potential cardiovascular risk association for ustekinumab treatment in patients at high cardiovascular risk specifically1. We use mendelian randomization (MR) to assess the reliability of this finding.

Methods

MR uses genetic variation to examine the causal effect of a risk factor (exposure) on a disease (outcome). The basis of MR relies on the use of genetic variants as instrumental variables (IVs) that are reliably related to the risk factor and that are not susceptible of reverse causation and confounding2. We use genetic variants (SNPs) detected in eQTL studies that affect gene expression levels as proxies for the IL12-IL23 pathway genes in order to simulate the biological effect of ustekinumab. A cardiovascular trait-composition composed of different groups of outcomes (acute coronary syndrome, transient ischaemic attack, unstable angina and ischemic stroke) was created to investigate further the possible association of ustekinumab with triggering cardiovascular events.

Results

Using top cis-eQTLs from the eQTLGen consortium and the Database of Immune Cell Expression (DICE) as IVs for the IL12-IL23 pathway genes, we observed non-significant associations after multiple testing correction for any of the cardiovascular traits. However, we observed a significant positive causal effect for IL12Rβ1 gene in acute coronary syndrome when using IVs from the Genotype-Tissue Expression (GTEx) project. An observation that was also obtained in a meta-analysis specifically for acute coronary syndrome. In addition, we run MR with multiple SNPs associated with IL12-IL23 genes and we did obtain similar results for IL12Rβ1 and acute coronary syndrome.

Conclusion

Our results suggest that the blockade of the IL12-IL23 pathway with ustekinumab might reduce cardiovascular risk and provide a cardioprotective effect based on the results obtained for acute coronary syndrome. As these results are not in line with previous observational studies1, further investigations are needed to clarify the biological mechanism that may account for these discrepancies.

1. Poizeau et al. JAMA Dermatol (2020).

2. Sanderson et al. Nat Rev (2022).
P908 Faecal Microbiota Transplantation refurbishes the crypt-associated microbiota in Ulcerative colitis
Authors: Markandey M , Bajaj A , Verma M , Virmani S , Singh M , Gaur P , Das P , Srikanth C , Makharia G , Kedia S , Ahuja V
Published: January 2023

Background

Intestinal crypts form a pristine gut biogeographical niche, homing the intestinal stem cells and being the closest neighbors to underlying lamina propria. Initially believed to be sterile, the crypt lumen was recently shown to inhabit a conserved microbial population. However, the identity of the crypt-associated microbiota (CAM) remains elusive. The present study is among the first to illustrate the CAM composition in health and its deviation during ulcerative colitis (UC), and the effect of faecal microbiota transplantation along with an anti-inflammatory diet (FMT-AID) on the structure of this community.

Methods

Recto-sigmoidal biopsies from controls, and from patients with mild-moderate UC before and after FMT-AID (n=26), were subjected to methacarn-fixation, followed by paraffin-embedding, sectioning and laser-capture microdissection-assisted crypt isolation. DNA isolated from micro-dissected samples was subjected to 16S rRNA gene sequencing. The bacterial presence in colonic crypts was confirmed using fluorescence in-situ hybridization(FISH). Microbiome data analysis was carried out by using QIIME2 and R packages.

Results

FISH performed using pan-bacterial probes revealed the presence of sparse microbial clusters in colonic crypts, distinct from the overlying layer of Mucosa-associated microbiota (MAM), in both controls as well as in UC(Fig.1a and 1b). While MAM is dominated by members of phyla Firmicutes (45%) and Bacteroidetes (26%),CAM is comprised predominantly of aerobic members of Actinobacteria(54%) and Proteobacteria(38%), followed by minor proportions of Firmicutes(4%), Acidobacteria and Cyanobacteria (2% each). The significant members of CAM included aerobic genera -Cutibacterium(35%),Sphingobium(13%), Paracoccus(11%), Micrococcus(3%), Lawsonella(3%), Rothia(2%), Prauserella(2%), Kocuria, Corynebacterium, Acinetobacter and Brevundimonas (1% each)(Fig.1c and 1d). Analysis of CAM diversity in controls, and in patients with UC before and after FMT-AID, showed no significant alterations in the α- and β diversity matrices(Fig.1e and 1f).CAM demonstrated UC-associated dysbiosis of specific taxa which was restored after FMT-AID(Fig.2a and 2b). These FMT-restored CAM taxa correlated negatively with disease-associated parameters - Fecal calprotectin (FCP), Simple Clinical Colitis Activity Index (SCCAI) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS)(Fig.2c and 2d). The positive effects of FMT-AID further refurbished the CAM-MAM interaction networks, which were obliterated in UC.(Fig.2e)

Conclusion

A gut bacterial community, enriched in aerobic bacteria, resides in the colonic crypts, and undergoes taxa-level alterations during UC and in response to FMT.
P910 Emerging role of IL-33/ST2 and Gut Microbiota axis in the inflammatory process of ulcerative colitis patients with ileal pouch-anal anastomosis
Authors: Lopetuso L R , Vetrone L , Petito V , Pugliese D , Parisio L , Laterza L , Gasbarrini A , Scaldaferri F , Papa A
Published: January 2023

Background

IL-33/ST2 axis and gut microbiota are important factors in the pathogenesis of IBD with a potential reciprocal influence. IL-33/ST2 axis controls the mucosal healing process during intestinal inflammation. Pouchitis, after restorative proctocolectomy with ileal pouch-anal anastomosis, is the most common complication. We aimed to explore the potential correlation between mucosal cytokines and gut microbiota in the inflammatory process of pouchitis.

Methods

23 patients with ileal pouch-anal anastomosis were enrolled. 13 showed pouchitis and 10 a normal pouch. Mucosal samples were collected from the afferent ileal loop and from the pouch. Multiplex analysis for cytokines was performed. ELISA, western blot and IHC were run to assess IL-33/ST2 axis. Microbiota was analyzed by 16S ribosomal RNA gene amplicon pyrosequencing. Pouchitis Disease Activity Index and Pouchitis Histological Score were calculated. Multivariate analyses were run to generate transcriptional interaction networks and identify biomarkers for patients with inflamed pouches.

Results

IL-1Ra, IL-6, IL-8, IL-17, IP-10, MCP-1, MIP-1a, MIP-1b were increased in the inflamed pouch vs. normal pouch. No differences were registered in samples from the afferent ileal loop. In pouchitis, IL-7 resulted reduced in the inflamed pouch vs. the ileal loop. In normal pouch, no differences were recorded. In pouchitis, IL-33 and ST2 protein levels were significantly reduced in the pouch vs. the ileal loop and resulted decreased vs. normal pouch. Full-length, bioactive IL33, ST2L and sST2 were expressed in all experimental groups; the cleaved, less active form of IL33 was increased only in pouchitis. IL-33 and ST2 stainings were less intense within the inflamed and ulcerated mucosa of pouchitis compared to the normal pouch and in close proximity to areas of re-epithelialization. Microbiota analysis showed a decreased biodiversity in pouchitis vs. normal pouch (both at pouch and ileal loop level). Lower levels of Verrucomicrobia and increased abundance of Actinobacteria were recorded in inflamed pouch vs normal pouch. In pouchitis, the ileal loop and the pouch showed decreased levels of Akkermansia muciniphila and augmented abundance of Collinsella vs. samples from the normal pouch. In pouchitis, multivariate analyses evidenced a significant inverse correlation between Collinsella e Collinsella aereofaciens abundance and ST2 levels.

Conclusion

Pouchitis and normal pouch are characterized by divergent inflammatory molecular pathways and microbial populations with a specific pattern between the pouch and afferent ileal loop. Our results suggest a potential role for IL-33/ST2 and gut microbiota axis in driving the gut mucosal wound healing in patients with ileal pouch-anal anastomosis.
P924 A unique gut microbiome signature can help differentiate Crohn`s Disease and isolated Terminal Ileitis
Authors: Raghunathan N , Joshi V , Patel R , Mekala D , Pal P , Banerjee R
Published: January 2023

Background

With increasing number of ileal intubations, isolated terminal ileal ulcers(TI) are often detected during colonoscopies. The etiology of these lesions have not been well-defined and differentiating TI from early Crohn’s Disease (CD) is a commonly encountered diagnostic challenge. CD is associated with significant dysbiosis; however, the gut microbiome of TI is poorly studied. We aimed to compare the gut microbial profile between CD and isolated non-specific TI.

Methods

Fecal samples were collected from treatment naïve patients (26 CD;13 TI) and healthy volunteers (29) without the use of antibiotics, probiotics, and prebiotics for at least 6 weeks. CD was confirmed by endoscopic and histological examination. TI was diagnosed based on isolated terminal ileal erosions/ulcers, normal small bowel endoscopy, non-specific inflammation with no granulomas/ cryptitis/crypt abscess on biopsy, and no history of NSAIDs. Fecal DNA was isolated and sequenced(16S-V4). Taxonomical classification was performed by Amplicon Sequence Variant approach and analysed by STAMP (Statistical Analysis of Metagenomic Profiles) using Welch`s T-Test. PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) was used for predictive metagenomics. Significant metabolic pathways were corrected by Storey FDR (q<0.05). Fecal Calprotectin (FCal) was measured using QuantOnCal rapid test.

Results

Microbiome data analysis revealed a progressive decline in α-diversity(p=0.002) in CD and different β-diversity (Bray-Curtis dissimilarity p=0.001) compared to TI and healthy(Fig1). Overall Firmicutes were lower(p=9.81e-4) while Desulfobacterota were higher(p=8.65e-3) in CD than TI(Fig2A). Faecalibacterium prausnitzii (p=0.04) and Roseburia inulinivorans (p=0.03) were markedly reduced while Parabacteroides distasonis (p=9.91e-3) and Bilophila wadsworthia (p=7.36e-3) were elevated in CD (Fig3). A microbial signature covering 8 non-overlapping taxa was deduced to distinguish CD and TI (3 taxa reduced, 5 elevated in CD compared to TI) (Fig2B). PICRUSt analysis indicated 18 significant metabolic pathways differentiating CD and TI. Bacterial stress alarmone PPGPP-MET was significantly higher in CD (p=2.04e-3) (Fig4). FCal was significantly higher in CD with mean value (±SD) as 549.12±390.4 and 167.15±191.8µg/g in TI (p=0.002).

Conclusion

A distinct gut microbiome profile was observed in TI compared to CD. Exploitation of these differences can potentiate differential diagnosis of CD and TI. Further research on the spectrum of dysbiosis is warranted. This may help in differentiating patients with early-CD who require active therapy from those with non-specific TI ulcers that resolve over time.
P927 Corticosteroid treatment in pediatric IBD patients reshapes the gut microbiota
Authors: Singh P , Sundararajan S , Terranegra A , Elawad M , Akobeng A , Al Khodor S
Published: January 2023

Background

Inflammatory bowel disease (IBD) in pediatric populations comprises 25% of all cases of IBD, which is a chronic immune-mediated inflammation of the intestinal tract. The clinical course of IBD is demonstrated in relapsing and remitting phases that require lifelong monitoring and treatment. The complex interactions between mucosal immunity and the intestinal microbiota are well-known in the pathogenesis of IBD. Corticosteroids are commonly administered to reduce IBD-associated mucosal inflammation and gastrointestinal symptoms. Whether or not corticosteroids beneficially modulate the mucosal microbiota to help reduce intestinal inflammation in pediatric patients with IBD has not been evaluated with interventional studies.

Methods

The objective of this study was to evaluate the effects of corticosteroids on the diversity and composition of gut microbiota in pediatric IBD patients. Ten pediatric patients diagnosed with IBD were treated with corticosteroids for 2-3 months. Stool samples were collected before and 8 weeks after treatment. The diversity and composition of gut microbiota were evaluated using 16S rRNA gene sequencing.

Results

Our results suggest that 3 months of corticosteroid treatment result in an increase in alpha diversity(p<0.05). The community structure of gut bacteria was significantly different (p<0.05) pre and post-treatment, with higher abundances of Bacteroides ovatus Bacteroides fragilis whereas the lower abundance of Prevotella copri and Alistipes finegoldi was observed(p<0.05). In conclusion, the diversity and composition of bacteria differ as a result of corticosteroid administration. Since gut microbiota plays an important role in regulating inflammatory conditions such as IBD

Conclusion

Reshaping intestinal microbiota through corticosteroid therapy may be a viable treatment option.
N04 How to manage the concerns of patients with inflammatory bowel disease due to the transition from in-hospital to home management with oral or subcutaneous therapies: results of a survey of a cohort of patients in intravenous biologic treatment
Authors: Napolitano D , Settanni C R , Parisio L , Schiavoni E , Pugliese D , Scaldaferri F , Gasbarrini A , Papa A
Published: January 2023

Background

Therapeutic armamentarium of inflammatory bowel disease (IBD) has expanded, including several intravenous (IV) and subcutaneously administered biological agents and orally administered small molecules (SMs). Additionally, some biologics initially available only for IV administration also have subcutaneous (SC) formulations. However, transitioning from in-hospital IV treatment to SC or oral home therapy can lead to some patient concerns, mainly linked to the need for self-administration and managing side effects. This study aimed to evaluate the opinion of IBD patients on the transition to oral or SC treatment, considering multiple socio-demographic factors, the frequency of biologic agent infusion, and the commitments (personal, family, work) associated with the in-hospital administration of therapy. In addition, patients were asked about their knowledge of new therapeutic options and their expectations about this management modality.

Methods

We conducted a survey using a questionnaire prepared by a team of gastroenterologists and nurses working at the IBD Unit of the CEMAD-Policlinico Gemelli of Rome. The survey was administered to consecutive IBD patients in stable IV biological treatment from January to October 2022. It consists of 31 items and has been divided into four sections: descriptive, commitment, knowledge and passage mode opinion.

Results

311 patients responded to the survey from 400 questionnaires (77.7%). 49.8% favored switching from IV to oral or SC therapy, and only 25.1% disagreed. In univariate and multivariate analysis, the home therapy approval rate was significantly associated with the distance from the IBD center (Fig. 1) and work/family/personal commitments. Surprisingly, only about a quarter of the IBD patients knew that almost all the following available therapeutic agents will have an SC administration route or will be SMs (Fig. 2). Regarding patients' opinion on the efficacy of SMs or SC administration of biological agents compared to IV drugs: 63% had no definite idea, while 14% believed that the effectiveness could be reduced. 23.8% of patients would like to be reassured by their gastroenterologist or nurse on the efficacy and safety of these new therapeutic options, and 7.7% would like to know the scientific data from studies on this issue.

Conclusion

The transition from in-hospital to the home therapeutic management of biological therapy with SC or oral agents was generally viewed favorably by patients, especially if they have commitments or are residents far from the IBD center. However, to reduce patient concerns and encourage this change, it is necessary to implement a patient training and information program involving all the IBD unit care figures, including IBD nurses.