bluuebunny/crossref_metadata_2025 huggingface dataset:
P042 Diagnostic and prognostic value of soluble adhesion molecules in patients with ulcerative colitis
Authors: Tarasova G , Dobaeva N , Iakovlev A , Volkov A
Published: May 2021

Background

Experimental studies have shown that cell adhesion molecules contribute to the constant induction of pro-inflammatory cytokines (interleukin (6, 8, 10), necrosis factor of tumor-α), providing the chronicity of immune-mediated inflammation at ulcerative colitis (UC). Determination of the importance of molecules of integrin adhesion (sVCAM-1) and mucosal adressin (sMAdCAM-1) for evaluating the effectiveness of treatment of patients with UC.

Methods

119 patients with UC were examined: 17 (14.3%) with proctitis, 44 (37%) with left-sided localization, 58 (48.7%) with the total form. The comparison group consisted of 20 healthy volunteers. Determination of serum sVCAM and sMAdCAM was carried out by quantitative enzyme-linked immunosorbent assay (ELISA) based on a system for multiplex analysis using flow fluorimetry — Luminex MAGPIX (USA), ICAM-1 kit (Cusabio, USA). The indicators were assessed before the start of the basic therapy course, in accordance with national recommendations, and 12 weeks after its completion.

Results

In patients with left-sided and total UC, a 3.2 and 4.7-fold increase in sVCAM expression and a 2.8, 3.6-fold increase in sMAdCAM expression was recorded, averaging: 386.6 + 21.2 ng/ml, 623.4 + 11.1 ng/ml; 116.5 + 13.6 ng/ml, 193.8 + 15.2 ng/ml, respectively (p <0.001). In the group with rectal lesions, there was a moderate increase in the expression of adhesion molecules: 157.1 + 11.3 ng/ml, 84.5 + 18.8 ng/ml, respectively (p<0.07). Against the background of a 12-week treatment course, clinical and endoscopic remission was recorded in 84 (70.6%) patients. In the groups of patients with left-sided and total UC in the drug remission phase, there was a decrease in the expression of sVCAM (194.6 + 9.2 ng/ml, 236.7 + 14.1 ng/ml) and sMAdCAM (72.4 + 8.1 ng/ml, 98.2 + 9.7 ng/ml), respectively (p <0.02). In cases with UC activity, increased levels of adhesion molecules persisted.

Conclusion

The soluble adhesion molecules of sVCAM and sMAdCAM are modern markers of inflammation that can be used for assessing the effectiveness of course therapy of UC.
P055 Brain-Immune Axis Regulation is Responsive to Cognitive Behavioral and Mindfulness-Based Stress Reduction in Crohn’s Disease
Authors: Nemirovsky A , Ilan K , Lerner L , Cohen-Lavi L , Schwartz D , Goren G , Sergienko R , Greenberg D , Slonim-Nevo V , Sarid O , Friger M , Regev S , Odes S , Hertz T , Monsonego A
Published: May 2021

Background

Crohn’s disease (CD) is a chronic inflammatory bowel disease associated with psychological stress that is regulated primarily by the pituitary-hypophysis-adrenal (HPA) axis. Here, we determined whether the psychological characteristics of CD patients associate with their inflammatory state, and whether a 3-month period of Cognitive Behavioral and Mindfulness-Based Stress Reduction (COBMINDEX) impacts their inflammatory process.

Methods

Circulating inflammatory markers (IFN-α, IFN-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL-12p70, IL-18, IL-23, and IL-33) and a wide range of psychological parameters were measured before (T1) and after (T2) COBMINDEX in CD patients. Inflammatory parameters were also compared to age- and sex-matched healthy controls (HCs) at T1, and to wait-list CD patients (at T1 and T2) who were followed for 3 months but did not receive COMBINDEX. Psychological symptoms were assessed by two questionnaires: the Perceived Stress Scale PSS4, and the Brief Symptom Inventory of psychological distress with Global Severity Index GSI. Statistical significance was assessed using Spearman correlation.

Results

CD patients (N=100, mean age 33.6 ± 13 years, 69% female, Harvey-Bradshaw Index mean 31± 55) exhibited increased peripheral low-grade inflammation compared with HCs, demonstrated by higher serum levels of interleukin (IL)-6 (mean 4.084± 8.4) and IL-18 (mean 302.09± 286) shown in Figure 1. Notably, IL-18 levels correlated with a higher stress score and a lower wellbeing score in CD patients (Figure 2). COBMINDEX was accompanied by changes in inflammatory markers that coincided with changes in cortisol: changes in serum levels of cortisol correlated positively with those of IL-10 (0.32, p<0.05) and INFα (0.36, p<0.05) and correlated negatively with those of MCP-1 (-0.34, p<0.05). Finally, baseline inflammatory markers of CD patients predicted COBMINDEX efficacy, as changes in HBI were negatively correlated with cytokines levels of IFNa (p=0.046), IFNg (p=0.03), IL-10 (p=0.002), IL-23 (p=0.025), IL33 (p=0.009) and IL12p70 (p=0.037) at T1 in the COBMINDEX group, but not in the wait-list group. In addition, basal levels of circulating cortisol at T1 negatively correlated with changes in GSI (-0.33, p<0.05) between T1 and T2 in the COBMINDEX group, but not in the wait-list group.

Conclusion

Our results show that CD patients have a characteristic immunological profile that correlates with psychological stress and disease activity, and predicts COBMINDEX outcomes. We suggest that COBMINDEX induces stress resilience in CD patients, which not only impacts their well-being, but also their disease-associated inflammatory process.
P070 Efficacy of a novel non-covalent oral small molecule Nrf2 activator in a rat model of Inflammatory Bowel Disease
Authors: Murray C , Cooper N , Lucas C L , Manso A S , Ray N C , Worthington J , Fox J C
Published: May 2021

Background

Inflammatory Bowel Disease (IBD) is characterised by chronic inflammation and increased oxidative stress in the intestinal mucosa of patients. NF-E2-related factor 2 (Nrf2) plays a key role in the antioxidant response by regulating the transcription of antioxidant genes as well as reducing expression of inflammatory mediators. A role for the Nrf2 pathway in IBD has been demonstrated in rodent models previously but these studies have predominantly used compounds such as Dimethyl Fumarate that are covalent Nrf2 activators that have the potential for significant off-target activities. C4X Discovery has identified C4X_6746, a novel potent and selective non-covalent Nrf2 activator, that disrupts the interaction between Nrf2 and its repressor Keap1 and is being investigated as an oral treatment for inflammatory disorders.

Methods

Male Han Wistar rats were given 3% Dextran Sodium Sulphate (DSS) in drinking water for 8 days in order to induce colitis and were dosed once daily by oral gavage with vehicle, C4X_6746 (0.3, 3 or 30 mg/kg) or Cyclosporine A (CsA, 20 mg/kg). The Disease Activity Index (DAI) was assessed daily based on stool consistency, faecal blood and body weight. On study termination, the colon weight and length were measured, and additional endpoints assessed (colon macroscopic score, histology, colon markers of inflammation and antioxidant response).

Results

C4X_6746 caused a dose-dependent decrease in the DAI with 30 mg/kg showing similar efficacy to the reference comparator CsA. C4X_6746 (3 and 30 mg/kg) resulted in a statistically significant reduction in the colon weight:length ratio and the macroscopic score. The compound also reduced the DSS-induced histological changes including inflammatory cell infiltrate, epithelial damage and mucosal architecture changes. Analysis of the colon tissue showed that C4X_6746 reduced inflammation (MPO activity) and upregulated the antioxidant response (SOD activity, ratio of reduced:oxidised glutathione). Efficacy of C4X_6746 in the model correlated with the dose-dependent induction of NQO1 mRNA in the colon and blood as a biomarker for Nrf2 pathway activation.

Conclusion

The efficacy of C4X_6746 in the rat DSS model supports development of non-covalent oral Nrf2 activators to significantly reduce oxidative tissue damage and chronic inflammation in IBD.
P087 The role of bile acids in mediating fibrosis in inflammatory bowel disease
Authors: Hazel K , McGinley N , O’Toole A , Keely S
Published: May 2021

Background

Crohn’s disease is a chronic inflammatory disorder of the gastrointestinal tract that affects approximately 15,000 people in Ireland. 10% of these patients will develop fibrostenosing disease, usually requiring surgery. There are currently no antifibrotic medications in use for the treatment of fibrostenosing CD.

Bile acids (BAs), produced in the liver and classically known for their roles in facilitating fat absorption from the diet, have previously been shown to have the capacity to regulate fibroblast activation and to exert protective effects against both hepatic fibrosis and intestinal inflammation. Therefore, altered mucosal fibroblast function in response to luminal BAs may be an important factor in the pathogenesis of fibrostenosing Crohn’s disease.

Our aim is to determine if treatment of fibroblasts under pro-fibrotic conditions with naturally occurring BAs decreases markers associated with fibrosis.

Methods

NIH/3T3, a murine fibroblast cell line, were treated with TGF-ß (5 ng/ml) to induce their activation and transition to myofibroblasts in the absence or presence of varying concentrations of the naturally-occurring BAs, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) over 24 hours. qPCR was employed to determine expression of alpha-smooth muscle actin (aSMA), an important marker for ECM deposition and fibrosis.

Results

Treatment of fibroblasts with DCA within the range of normal physiological concentrations (50 to 200 µM) induced a significant inhibition of TGF-ß-induced aSMA expression. At a concentration of 100 µM, DCA reduced TGF-ß-induced responses by 50%, compared to cells treated with TGF-ß-alone (RQ=2.17; RQ=4.58, respectively) (n=6) (p=0.0031) (Figure 1). Similarly, treatment with UDCA at supraphysiological concentrations (500 µM) decreased aSMA expression following TGF-ß stimulation (RQ=1.75; RQ=3.69, respectively) (n=5) (Figure 2). Treatment with conjugated BAs TDCA and TUDCA suggest an intracellular mechanism of action by DCA and UDCA. INT-777, the specific agonist of the TGR5 bile acid receptor, also reduced TGF-ß-induced aSMA expression, suggesting this receptor may be involved in mediating the effects of naturally-occurring BAs.

Figure 1:

Figure 2:

Conclusion

We have shown that treatment of fibroblasts under pro-fibrotic conditions with the BAs, DCA and UDCA, results in a significant decrease in aSMA expression. These data suggest that BAs represent a promising target for the development of new anti-fibrotic agents to treat/prevent fibrostenosing CD.
P089 IFNγ-macrophages could mediate EMT in Crohn’s disease
Authors: Marín-Aracil J , Barrachina M D , Bauset C , Cosin-Roger J , Coll S , Calatayud S , Antonio L S , Ortiz-Masiá D
Published: May 2021

Background

Macrophages contribute to fibrosis by releasing different mediators and the pattern of secretion may vary depending on the surrounding environment. We previously described that the mRNA expression of IFNγ was significantly higher in intestinal samples from CD patients. The aim of the present study is to analyze the role of IFNγ-treated macrophages in epithelial mesenchymal transition (EMT).

Methods

The mRNA and protein expression of IFN in surgical resections from Crohn′s disease. U937 were differentiated to macrophages and then treated with IFNγ (2 ng/ml) for 4 days, the mRNA expression of macrophages markers were determined by RT-PCR. IFNγ-U937 were coculture with HT29 cells for 2 days and the expression of EMT markers in HT29 cells were analyzed by RT-PCR and WB. Results are expressed as mean±SEM (n≥5). Statistical analysis was performed by ANOVA + Newman-Keuls.

Results

The mRNA and protein expression of IFNγ were significantly higher in intestinal samples from B2 CD patients (11.4±1.6 fold induction and 3.5±0.3 pg/mg, respectively) and B3 CD patients (14.2±1.8 fold induction and 3.1±0.1 pg/mg, respectively) than in controls (1,0±0,1 fold induction and 0.8±0,1 pg/mg, respectively). U937 cells treated with IFNγ increased significantly the mRNA expression of CD16 (1.9±0.2* vs vehicle) and CD86 (1.6±0.1* vs vehicle). IFNγ-U937 cocultured with HT29 increased significantly the mRNA and protein expression of EMT markers in HT29 cells (Vimentin: 3.0±0.5* vs vehicle-HT29; αSMA: 24.4±8.3* vs vehicle-HT29; SNAIL1: 2.7±0.5* vs vehicle-HT29) respect IFNγ-HT29 cells (Vimentin: 0.6±0.01 vs vehicle-HT29; αSMA: 1.1±0.4 vs vehicle-HT29; SNAIL1: 0.7±0.06 vs vehicle-HT29).

Conclusion

IFNγ could be responsible for the increase in the number of CD86/CD16 macrophages in CD patients. A macrophage phenotype expressing CD86/CD16 may act as a source of EMT mediators in intestinal tissue from CD patients.
P097 Abnormal frailty screening is independently associated with both all-cause and disease-related hospital admissions in older patients with inflammatory bowel diseases
Authors: Asscher V , Waars S , Fens J , Wieland M , van der Meulen-de Jong A , Stuyt R , Baven-Pronk M , van der Marel S , Jacobs R , Haans J , Van Deudekom F , Mooijaart S , Maljaars J
Published: May 2021

Background

Frailty could be useful for risk stratification in older patients with Inflammatory Bowel Diseases (IBD). However, no prospective evidence is yet available. We aimed to assess how frailty screening associates with hospital admissions and functional and (health related) quality of life (HR)QoL decline.

Methods

This is a prospective multicenter cohort study. Consecutive IBD patients aged ≥65 years were included at outpatient departments and infusion centers in six hospitals. Clinical disease activity was assessed through Harvey Bradshaw Index (HBI) or partial Mayo Score (pMS) (remission: HBI<5 or pMS<2), biochemical disease activity by C-reactive protein ≥10 mg/L and/or calprotectin ≥250 µg/g. Frailty screening was performed by Geriatric 8 (G8) questionnaire (abnormal: ≤14). At 18 months, data regarding hospital admissions and mortality were retrieved from medical records and, when possible, verified during follow-up visits. Functional status (Katz Index of Independence in Activities of Daily Living (ADL) and Lawton Instrumental Activities of Daily Living (IADL)) and (HR)QoL (short Inflammatory Bowel Disease Questionnaire and EuroQol-5D) were assessed at baseline and follow-up. Hospital admissions were analyzed with Kaplan Meier and Cox regression, functional and (HR)QoL decline with logistic regression. Analyses were corrected for age and biochemical disease activity.

Results

405 patients were included, median age 70 (IQR 67–74), 85 (21%) clinical disease activity, 93 (23%) biochemical disease activity and 196 (48%) abnormal G8. Until February 2021, 293 (72%) patients were eligible for follow-up: 255 participated in follow-up visits, 38 patients did not (15 not reachable, 16 not willing, 7 died). 74 all-cause and 33 IBD-related hospital admissions occurred. Abnormal G8 was associated with occurrence of both all-cause (adjusted HR 3.9, 95%CI 1.9–7.8, p<.001, Fig. 1) and IBD-related hospital admissions (adjusted HR 4.1, 95% CI 1.4–12.3, p=0.012, Fig. 2). Seven patients died during follow-up; six had abnormal G8. 19 (37%) out of 51 patients with both active biochemical disease and abnormal G8 were hospitalized compared to 4 (14%) out of 29 patients with active disease and normal G8 (p=.026). Abnormal G8 associated with functional (IADL: aOR 3.0, 95% CI 1.3–6.9, P.009, ADL: aOR 1.6, 95% CI 0.7–3.3, p.241) and QoL decline (EQ5D: aOR 2.4, 95% CI 1.4–4.3, p.002), not with HRQoL (sIBDQ: aOR 1.3, 95% CI 0.8–2.2, p=.336).

Conclusion

Abnormal frailty screening independently associates with both all-cause and IBD-related hospital admissions and with functional and QoL decline. Therefore, we provide the first prospective evidence for frailty screening as a useful risk stratification tool in IBD.
P126 Older adults with acute severe ulcerative colitis have similar steroid failure and colectomy rates as younger adults
Authors: Kakkadasam Ramaswamy P , Subhaharan D , Edwards J , Willmann L , Shukla D , Moattar H , Bhullar M , Dorrington A , Ishaq N , McIvor C , Mohsen W
Published: May 2021

Background

There is paucity of data on the outcomes of Acute Severe Ulcerative Colitis (ASUC) in older adults (≥60 years of age). The primary objective of our study was to assess steroid failure rate. The secondary outcomes assessed were need for colectomy during same admission, at 3 and 12months; mortality during admission for ASUC, at 3 months and 12months. Outcomes were compared with younger adults (< 60 years).

Methods

All admissions for ASUC (fulfilling Truelove and Witts Criteria) between January 1, 2013 and July 31st, 2020 at two Australian tertiary IBD centres were retrospectively analysed. Review of electronic medical records was performed and clinical, endoscopic, laboratory data were collected. Non-parametric data were compared using Kruskal-Wallis test. Parametric data were compared using paired t-test.

Results

226 episodes of ASUC were analysed, 45 episodes were in patients who were ≥ 60 years of age at the time of ASUC event. Median Charlston comorbidity index was 3 (IQR: 2–4). In older adults, 19 (42.2%) failed intravenous steroid therapy and required rescue therapy. 2 (10.5%) episodes underwent direct colectomy, 17 episodes received medical rescue therapy (11 infliximab, 6 ciclosporin); 7 (63.6%) episodes received IFX 5mg/kg, 4 episodes (36.4%) received IFX 10mg/kg. 6 (13.3%) episodes had a colectomy during the admission for ASUC; 9 (20.9%) episodes had colectomy within 3 months and 9(20.9%) episodes underwent colectomy within 12 months. In patients < 60 years of age, steroid failure rate was 46.9% (85/181), 10.5% (19/181) underwent colectomy during the same admission, 17.6% (30/181) underwent colectomy by 3 months and 28.8% (42/181) had undergone colectomy at 12 months. In older adults, mortality during same admission occurred in 1 (2.2%) patient, 3-month mortality was 6.8% (3 patients) and 12-month mortality was 11.4% (5 patients). There was no mortality in patients < 60 years of age.

Conclusion

In older adults, steroid failure, the need for colectomy during the same admission and colectomy at 12 months is similar to a population <60 years of age. Mortality (at 3 and 12 months) is significantly higher.
P160 Can the Lemann index at diagnosis predict the risk of early surgery in Crohn’s disease?
Authors: Hassine A , Akkari I , Mrabet S , Ben Jazia E
Published: May 2021

Background

Identifying patients with Crohn’s disease (CD) with rapid disease progression or at high risk for early surgery is a crucial pillar in the treatment decision to ensure optimal patient management. The objective of this study was to assess the correlation between the Lemann index at the time of diagnosis and abdominal surgery in the first year after diagnosis of Crohn’s disease and to find the risk factors for early surgery.

Methods

This is a retrospective study of all patients with CD followed in our center over a period of 4 years (January 2016- January 2020), and who were evaluated by endoscopy and MRI at baseline. The Lemann Index is a score that measures cumulative damage to digestive tissue from entero-MRI and endoscopy data. It was calculated by noting the previous surgery, the location and extension of the disease and any intestinal complications. The sociodemographic and clinical characteristics of the patients were studied. Hypothesis tests were applied to identify associations.

Results

112 patients with CD were included in this study, of which 53.6% were female. The mean age at diagnosis was 33.29 years [15–63]. Active smoking was found in 34 patients (30.4%). Regarding the localization of CD, it was ileal (L1 according to the Montreal classification), colonic (L2), and ileocolonic (L3) in respectively 16.1%, 42.9% and 41%. The disease phenotype was inflammatory (B1) in 60.7%, stricturing (B2) in 21.42%, and penetrating (B3) in 17.85%. Anoperineal manifestations were noted in 24 patients. An upper digestive tract was present in 19.6% of patients. The initial flare was judged to be severe in 33.9% of cases, moderate in 55.4% of cases and mild in 10.7% of cases, with a mean CDAI of 305.21 [115–493]. During the first year after diagnosis of CD, 19.6% of patients (n = 22) required surgical treatment. The indications for surgery were: the presence of an intra-abdominal collection (27.3%), severe acute corticosteroid-resistant colitis (18.2%); ileocaecal stenosis resistant to medical treatment (27.3%) or acute bowel obstruction (27.3%). The LI at diagnosis was much higher in the early surgery group: 5.22 +/- 2.65 vs. 2.63 +/- 1.88; with a statistically significant difference (p = 0.01). A severe initial flare as well as a penetrating phenotype were predictors of early abdominal surgery (p = 0.022, p = 0.024, respectively).

Conclusion

According to our study, a high Lemann score at diagnosis correlates well with the risk of early surgery in Crohn’s disease. Further, larger-scale studies would be needed to establish the reliability of this test in predicting this risk.
P170 Correlation between health-related quality of life and smartphone-based self-assessment of activity index in patients with ulcerative colitis
Authors: Park J J , Jung Y , Na S Y , Lee Y J , Kim J W , Kim N H
Published: May 2021

Background

E-health platform can facilitate remote monitoring of ulcerative colitis (UC) patients. A recent study shows that patient-administered simple clinical colitis activity index (SCCAI) via online correlated well with physician-assessed SCCAI. We evaluated the correlation between the self-administered SCCAI through smartphone and health-related quality-of-life assessment.

Methods

Clinical disease activity was assessed by the SCCAI and health-related quality of life by the disease-specific, self-administered Inflammatory Bowel Disease Questionnaire (IBDQ). Patients were followed-up over six months. At months 3 and 6, patients completed SCCAI through access to the web-based system (PROscore system) via link sent by text message to the smartphone at the outside of the hospital; within 48 h, patients subsequently completed the questionnaire of IBDQ in the clinic and attending gastroenterologist (blinded to patients’ scores) assessed the in-clinic SCCAI (reference). SCCAI scores were categorized into remission or active disease.

Results

A total of 157 patients (median age: 41 years; 62% male) contributed with 310 pairs of questionnaires. SCCAI scores by patients inversely correlated well with IBDQ (Pearson’s ρ =0.39). Moreover, linear regression revealed that this correlation persists irrespective of patient age, gender, disease extent, and education status. Correlation of SCCAI scores by patients and physicians was good (Spearman’s ρ =0.36), with 66% agreement for remission or active disease. The negative predictive value for the active disease was 84.3%; the positive predictive value was 41.2.0%.

Conclusion

In patients with UC, self-administered SCCAI via smartphone showed a good correlation with physician assessed disease activity and the patient’s quality of life. This validated e-health platform may be useful in remote monitoring of UC patients.
P192 Frequency of hereditary and acquired thromboembolic complications in patients with inflammatory bowel diseases in Moscow Clinical Scientific Center named after A.S. Loginov
Authors: Knyazev O , Lishchinskaia A , Kagramanova A , Zvyaglova M , Noskova K , Kulakov D , Parfenov A
Published: May 2021

Background

Thromboembolic complications (TC), which are one of the characteristic manifestations of inflammatory bowel diseases (IBD).

Objective

to identify the frequency of acquired and inherited hypercoagulation factors that contribute to the development of TC in patients with IBD.

Methods

The clinical status of 1238 IBD patients undergoing treatment in 2019 was evaluated in the Department of IBD. 748 patients with ulcerative colitis (UC) and 490 patients with Crohn’s disease (CD). In 112 patients with IBD (9.0%), clinically significant TC (venous thrombosis of the lower extremities, upper extremities and others) was detected. In patients with clinically significant feasibility studies, DNA isolated from peripheral blood lymphocytes was examined to identify molecular genetic mutations that lead to hypercoagulation.

Results

Of the 112 patients with TC, 76 (67.8%) patients had UC, and 36 (32.2 %) patients had Crohn’s disease. Of 112 IBD patients with clinically significant TC, 45 (40.2 %) had genetic mutations that increase affinity for fibrinogen, increase platelet aggregation, disrupt folic acid metabolism, and reduce the activity of the methylentetrahydrofolate reductase enzyme, which may be manifested by a moderate increase in homocysteine levels. 67 patients with IBD (59.8%) did not have genetic mutations that lead to hypercoagulation. Of the 45 IBD patients with clinically significant feasibility studies due to hereditary factors, 30 (66.6%) patients had UC, 15 (33.7%) patients had CD (RR-1.038, 95% CI 0.746–1.444; x2-0.049; p=0.83921).

Conclusion

Clinically significant feasibility studies were found in 9.0% of IBD patients. More than 40% of patients with clinically significant feasibility studies (n=112) have inherited factors that contribute to the development of feasibility studies. About 60 % of IBD patients with clinically significant feasibility studies do not have hereditary factors that lead to the development of feasibility studies.
P210 Healthcare resources utilisation prior to the diagnosis of ulcerative colitis and Crohn’s disease
Authors: Rodríguez-Lago I , Agirre U , Intxaurza N , Cantero D , Barreiro-de Acosta M , Cabriada J L
Published: May 2021

Background

Ulcerative colitis (UC) and Crohn’s disease (CD) are two chronic conditions of the gastrointestinal tract. Previous data suggest that a subclinical inflammatory process precedes the initial symptoms. Our aim was to determine if patients with UC or CD have an increase in healthcare utilization in the years preceding the disease onset.

Methods

A single-centre retrospective case-control study was performed at Hospital de Galdakao (Spain). We included all consecutive patients with a new diagnosis of UC/CD between 01/01/2018 and 31/12/2019. Cases were matched 1:3 with controls adjusted by sex, age and date, excluding those subjects with any visit to Gastroenterology Department. The main outcomes were the number of outpatient or Emergency visits, hospital admissions, radiological examinations (ultrasound, CT, MRI), sick-leaves, and prescriptions (antibiotics, steroids) in the 5 years before the diagnosis of UC/CD. Descriptive statistics were used, followed by chi-square tests and a multivariable hurdle regression model, adjusted by smoking habits and Charlson index, in order to perform a per year analysis. Additional grouped comparisons of the preceding 3 and 5 years were performed, and also excluding the 12 months prior to diagnosis.

Results

A total of 305 cases were included (160 UC, 168 CD; median 48 years; 53% female) and compared with 915 controls. Baseline characteristics including age, smoking habits, and comorbidities were comparable. Grouped analysis (excluding 12 months prior to UC/CD diagnosis) are summarized in Table 1. Patients had an increase in the number of hospital admissions, visits to the Emergency room or Primary Care physician, sick-leaves, radiological examinations, and prescription of antibiotics or corticosteroids in the previous 3 to 5 years, excluding the 12 months prior to diagnosis of UC/CD.

Conclusion

Patients with UC and CD show an increased use of healthcare resources in the years prior to the diagnosis. Diagnostic tools should focus in early predictors of disease onset as they may prompt an earlier identification of patients with IBD.
P219 An application of artificial intelligence in Inflammatory Bowel Disease detection
Authors: Rasmagina I , Bakulin I , Mariya S
Published: May 2021

Background

Inflammatory bowel disease (IBD) is verified on the basis of complex assessment of clinical, laboratory, endoscopic and morphological data. However, due to the lack of a ‘golden’ standard and similarity of the clinical picture, it usually takes more than 1 year to diagnose ulcerative colitis (UC) and more than 2 years for Crohn`s disease (CD). The aim of the study is to optimize the existing methods in diagnosis of IBD with an application of an artificial neural network (ANN).

Methods

216 patients with verified IBD (163 – UC, 53 – CD of large bowel) and 34 patients without endoscopic findings underwent colonoscopy in the Peter the Great Clinic of Mechnikov North-Western State Medical University (Saint-Petersburg, Russia). During the endoscopic examination 856 images were obtained: 268 images of “normal mucosa”, 194 ones of CD of large bowel and 394 ones of UC. The study included images of mild, moderate and severe activity of IBD. Mayo endoscopic score was used to assess endoscopic activity of UC. For CD the scoring scales were not provided, the activity of the disease was based on the length of the affected segment, presence of erosions, ulcers and complications such as strictures, fistulae and stenosis. All images were captured in high-resolution with the same endoscope (Olympus) and stored in a jpeg format. Poor-quality images resulting from blurs, defocus and poor air insufflation were excluded. We also created the ANN using the Neural Network Toolbox application from the MATLAB application package. The ANN consisted of 2 models: the first one was multilayer perceptron which determined a presence of pathology, the second was convolutional neural network which differentiated the types of IBD (UC or CD).

Results

All the endoscopic images were downloaded to the created ANN. It was trained 3 times due to the decrease of its accuracy. The average accuracy of the developed model in differentiation of pathology was 77%. This result could be associated with an insufficient number of CD images or ANN training on continuous data set of images with UC and CD features without clustering them to particular patient.

Conclusion

We conclude that the developed ANN shows moderate accuracy in recognition of different forms of IBD. This study has a limitation as the images were taken only with endoscope Olympus. Enlarged sample size and inclusion of morphologic images are needed in order to improve the accuracy of ANN.
P249 What’s the role of anti-TNF α in correcting anemia in Crohn’s disease?
Authors: Hassine A , Hammami A , Jaziri H , Elleuch N , Ksiaa M , Ben Slama A , Jmaa A
Published: May 2021

Background

Anemia is the most common extra intestinal complication in Inflamatory Bowel Diseases (IBD) affecting the quality of life of patients. Iron deficiency and inflammation are the two most common mechanisms. It has been suggested that controlling disease activity is sufficient to correct well-tolerated anemia. Anti-TNF α by their powerful anti-inflammatory action and their role in increasing the growth of erythroid progenitors can lead to correction of anemia. The aim of this work was to determine the effect of anti-TNFα on the course of anemia in Crohn’s disease (CD).

Methods

This is a single-center retrospective study including patients followed for CD, between 2011 and 2017, on anti-TNF. Anemia was tested in these patients before the initiation of anti-TNF. After six months of treatment, a correlation between the achievement of therapeutic efficacy and the correction of the anemia was sought. The judgment criteria adopted were: clinical response (CDAI score <150 points), mucosal healing at endoscopy (absence of ulcerations), and normalization of the C-reactive protein (CRP <5mg / l).

Results

120 patients were included, 60% of whom are female. The mean age at diagnosis was 29.8 years [12–56 years]. The mean duration of the disease was 7.42 ± 4.8 years. The disease phenotype was penetrating in 55% of cases and structuring in 45% of patients. Anoperineal manifestations (PAD) were noted in 20% of patients. 50% of patients were on Adalimumab, 50% on Infliximab and 45% of cases were on combination therapy. The indications for Biotherapy were: the presence of anoperineal manifestations (20%), failure of immunosuppressants (25%), postoperative recurrence (20%), intolerance to immunosuppressants (20%), and extradigestive manifestations in particular articular (15%). Pre-therapy, anemia was noted in 84 patients (70%), most of whom had chronic microcytic hypochromic anemia. The presence of anemia was well correlated with disease activity (p = 0.038). During the control, correction of anemia was obtained in 72 patients (60%), with a statistically significant association with the therapeutic efficacy criteria (clinical response: p <10–3, mucosal healing: p = 0.009, normalization of CRP: p <10–3).

Conclusion

Our study showed the effectiveness of anti-TNF alpha agents in correcting anemia in Crohn’s disease. Larger scale studies are needed to confirm our results.
P261 Predictors and outcomes of ustekinumab dose escalation to every 4 or every 6 weeks in ulcerative colitis: a multicenter cohort study in the United States
Authors: Dalal R , Esckilsen S , Barnes E , Pruce J , Marcus J , Allegretti J
Published: May 2021

Background

Patients with ulcerative colitis (UC) on ustekinumab (UST) therapy may have suboptimal response to standard every 8 week (q8w) dosing. Empiric dose escalation to q4w or q6w is common, but the efficacy of these strategies are unknown in UC. We performed a multicenter cohort study to identify predictors and outcomes of UST dose escalation in UC.

Methods

This retrospective cohort study included adults initiating UST for UC (ICD-10-CM 51x) at three academic medical centers in the United States 1/1/2016-11/1/2021. Patients with prior colectomy were excluded. Disease activity was assessed using the 9-point Mayo score or simple clinical colitis activity index (SCCAI) in electronic health records. Independent variables included demographics, UC duration, extraintestinal manifestation, medication/substance use history, endoscopic extent/severity, reason for escalation, intravenous (IV) reinduction, dose interval, albumin, C-reactive protein, and bowel frequency. The primary outcome was steroid-free clinical remission (SCCAI/Mayo <3 points) 12–16 weeks after escalation. Secondary outcomes were clinical response (reduction in SCCAI/Mayo by ≥3 points from baseline) at 12–16 weeks and time to escalation. Additional endpoints included endoscopic response, failure within 16 weeks (treatment discontinuation or colectomy), improvement in fecal calprotectin, UC hospitalisation, and adverse events. Multivariable logistic and cox regression were used to identify factors associated with remission and time to escalation, respectively.

Results

108 UC patients initiated UST: 91.7% had prior anti-TNF exposure and 57.4% were taking oral steroids (Table 1). 39.6% (40/101 with data) achieved remission 12–16 weeks after induction. 42.6% (46/108) were escalated to q4w (n=33) or q6w (n=13) after median of 95 days (IQR 65–208 days) primarily for no/minimal response to induction (22/46) or loss of response (20/46) (Fig 1A). 55.0% (22/40 with data) achieved remission at 12–16 weeks, 67.5% (27/40) had response, 56.3% (9/16 with data) had endoscopic response (Table 2), and 30.0% (12/40) had treatment failure (Fig 1B). 10.0% (4/40) were hospitalised after median of 80 days and 5.0% (2/40) had adverse events (urinary tract infection and C. difficile infection). After multivariable analysis, lack of response to induction was inversely associated with remission after escalation. Bowel frequency and >2 prior biologics were associated with time to escalation (Table 3).

Conclusion

UST dose escalation resulted in clinical remission in >50% of UC patients and was more effective in those with loss of response compared to no/minimal response after induction. Prospective studies are needed to identify UC subpopulations that will benefit from various dosing strategies of UST.
P276 Influence of vedolizumab on extraintestinal manifestations in Inflammatory Bowel Disease: a nationwide multicenter study of the GETECCU Eneida registry
Authors: Pérez Galindo P , Gisbert J P , Carrillo-Palau M , Bertoletti F , González-Vivó M , Ferrer J A , Pajares R , Merino O , Castaño A , Chaparro M , Calvo M , Barreiro-de-Acosta M , Rodríguez A , Lorente R H , Algaba A , Riado D , Vela M , De-la-Maza S , Llaó J , Vega P , Utrilla A , Almela P , Carpio D
Published: May 2021

Background

Evidence regarding vedolizumab (VDZ) influence on extraintestinal manifestations (EIMs) in inflammatory bowel disease patients (IBD) is scarce. Our aim was to analyze the effectiveness of VDZ in pre-existing EIMs and the occurrence of de novo EIMs during VDZ therapy in IBD.

Methods

We performed an observational, multicenter, retrospective cohort study including patients from the Spanish ENEIDA registry promoted by GETECCU. We retrospectively identified 551 patients from 20 centers. The co-primary outcomes were to evaluate the response of EIMs to VDZ and to assess the frequency of de novo EIMs during therapy. Secondary outcomes were to analyze associated factors with EIMs response to VDZ, time from VDZ initiation to occurrence of de novo EIMs and the discontinuation rate of VDZ because of worsening/de novo EIMs. Response and worsening of IBD and EIMs were defined by clinical and laboratory criteria according to the physician’s assessment.

Results

The median age of the cohort was 49.7 years (IQR 38-60), 50.8% were female, 50.8% had Crohn’s disease and 90.4% had prior biologic exposure (more than 1 biologic drug in 57.9%). At baseline 133 patients (24.1%) had pre-existing EIMs of whom 21 showed more than 1 EIM; 76.7% of EIMs were articular and 31% cutaneous. Regarding 77 patients with active EIMs at baseline, response of EIMs to VDZ at 3 months was observed in 23 (29.9%), worsening in 13 (16.9%) and no change in 41 (53.2%). Response rates for active EIMs were 35.4% for peripheral arthritis (PA), 11.8% for axial arthropathy (AA), 35.7% for cutaneous EIMs and 33.3% for ocular EIMs. Response of IBD at 3 months was the only associated factor with response of EIMs to VDZ (OR=3.72; CI 95% [1.08-12.83]). Among 56 patients with inactive EIMs at baseline, worsening of EIMs was observed in 5 patients after 12 months of VDZ therapy (13.5%) (3 cases of PA and 2 of AA). During follow-up 25 patients (4.5%) developed 27 de novo EIMs (17 cases of PA, 4 of AA, 4 of erythema nodosum, 1 of pyoderma gangrenosum and 1 of episcleritis). Median time from VDZ initiation to onset of de novo EIMs was 244 days (IQR 115-693). Presence of more than 1 pre-existing EIM was the only associated factor with de novo EIM onset during first year of VDZ therapy (OR=14.5; 95% CI [3.3-62]). Worsening of pre-existing EIMs or de novo EIMs was the cause of VDZ discontinuation in 15 patients (5.8% of all patients who discontinued VDZ).

Conclusion

VDZ achieved clinical response of active EIMs in nearly a third of patients after 3 months of therapy, being the response of IBD to VDZ the only associated factor. Worsening of inactive EIMs or de novo EIMs during VDZ therapy was infrequent.
P282 High plasma oncostatin-M predicts non-response to tumour necrosis factor-alpha antagonists in inflammatory bowel disease
Authors: Guo A , Ross C , Chande N , Gregor J , Ponich T , Beaton M , Khanna R , Kim R , Wilson A
Published: May 2021

Background

The interleukin-6 family cytokine, oncostatin-M (OSM) has been associated with a lack of remission to tumor necrosis factor-α antagonists (anti-TNFs) in small cohorts of patients with inflammatory bowel disease (IBD). We aimed to further evaluate the association between plasma OSM concentrations and response to anti-TNFs (infliximab and adalimumab) in addition to other clinical outcomes in both ulcerative colitis (UC) and Crohn’s disease (CD).

Methods

A retrospective cohort study was carried out in patients with IBD with a history of anti-TNF exposure. Blood samples, collected prior to anti-TNF exposure, were analyzed by enzyme-linked immunosorbent assay for the presence and quantity of OSM. The primary outcome evaluated was clinical remission at 1-year based on the Harvey Bradshaw Index (HBI, remission, HBI<5) for CD and the Partial Mayo Score for UC (remission, Partial Mayo Score<2). Data pertaining to the occurrence of surgery, hospitalization, corticosteroid use, and adverse drug events during the 1-year follow-up period were also collected. Lastly the threshold OSM plasma concentration associated with anti-TNF non-response was assessed by receiver operator characteristic (ROC) curve analysis.

Results

One hundred and fourteen patients with IBD (CD, n=73; UC, n=40) seen at a tertiary care centre in London, Ontario Canada, were included in the analyses. Patients received one of infliximab (n=61) or adalimumab (n=53). For those with UC achieving clinical remission at 1-year (n=24), the mean OSM concentration was 84.5±119.7pg/ml versus those not achieving clinical remission (n=16) where the mean OSM concentration was 1064.0±958.8pg/ml (p<0.0001). For those with CD, the mean OSM concentration was 116.3 ± 222.3pg/ml in those achieving clinical remission (n=52) versus those did not (n=22) where the mean OSM concentration was 1220.0 ± 1274.0pg/ml (p<0.0001).

A threshold OSM concentration of 168.7pg/ml in CD and 233.6pg/ml in UC separated those who achieved clinical remission at 1-year on an anti-TNF from those who did not (CD: area under the receiver operator characteristic curve, AUROC=0.880, 95%CI=0.79-0.96, p<0.0001; UC: AUROC=0.938, 95%CI=0.87-1.00, p<0.0001).

In CD, participants with a plasma OSM concentration above the threshold concentration of 168.7pg/ml, were more likely to discontinue their anti-TNF at 1-year (p<0.0001), require hospitalization (p=0.0019) and/or corticosteroid rescue therapy (p<0.0001), require a surgical intervention (p=0.0087) or experience a drug-related adverse event (p=0.009).

Conclusion

OSM plasma concentrations were associated with response to anti-TNFs at 1-year in IBD. A threshold OSM concentration of 168.7pg/ml distinguished patients with CD at-risk of poor clinical outcomes.
P306 MORF-057, an oral selective α4β7 integrin inhibitor for Inflammatory Bowel Disease, leads to specific target engagement in a single and multiple ascending dose study in healthy subjects
Authors: Ray A , Cui D , Lee D , Mangada M M , Jones J , Bain G , Traber P G , Vrishabhendra L H , Krzeski P W , Vande Casteele N , Reardon M M , Stern T P , Soo C L , Nguyen H , Rogers B N , Linde P G
Published: May 2021

Background

MORF-057 is an orally administered small molecule designed to inhibit the α 4β 7 receptor, addressing an unmet medical need in inflammatory bowel disease (IBD) patients, and avoiding the need for periodic therapeutic infusions and the risk for infusion-related reactions. This study evaluated single (SAD) and multiple ascending doses (MAD) of MORF-057 in healthy volunteers.

Methods

This was a randomized, double-blind, placebo-controlled, single and multiple doses, phase 1 study of the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of MORF-057 conducted in a Phase I Unit in the USA. Subjects were randomized 3:1 to MORF-057 or placebo capsules once daily in the SAD cohorts: 25, 50, 100, 150, and 400 mg; or twice daily (BID) in the MAD cohorts: 100 and 200 mg total daily doses (dosed as 50 and 100 mg BID, respectively). In the MAD cohorts, trough PK samples were obtained premorning or pre-evening dose following administration of 50 or 100 mg BID, respectively. Blood samples to assess receptor occupancy (RO) of α 4β 7 and α 4β 1 integrins were obtained prior to the first dose and 12 hours after treatment.

Results

To date, 51 healthy subjects were dosed; 1 subject withdrew consent on Day 2 for personal reasons. Eleven non-serious adverse events (AEs) were reported; AEs were mild and did not result in discontinuation. Two reversible mild AEs in the 200 mg MAD cohort were possibly related to MORF-057 (macular / maculopapular rash). No safety signals were identified to date. Following dosing, MORF-057 was rapidly absorbed and systemic exposure increased approximately dose-proportionally (Fig.1). Mean α 4β 7 RO was found to be greater than 95% after each of the three highest single doses (Fig.2). In multiple dosing, mean α 4β 7 RO was greater than 90% at the lower dose, while the highest dose tested resulted in α 4β 7 RO saturation at steady state. α 4β 1 RO was below the limit of quantitation with mean trough values estimated to be <10% at any of the dose levels.

Conclusion

Current results demonstrated that single and multiple ascending doses of MORF-057 were well tolerated, with only mild, non-serious AEs reported that did not result in study drug discontinuation. MORF-057 demonstrated a favorable PK profile where target engagement was confirmed and resulted in α4β7 receptor saturation in many subjects receiving higher doses. These results support further investigation of MORF-057 and provide a basis for dose selection phase 2 studies in patients with IBD. (NCT04580745)
P339 Pregnant women with perianal Crohn’s Disease: suggestions for the improvement of the current guideline on delivery method
Authors: Schaafsma I , Hoogenboom F , Visschedijk M , Prins J , Dijkstra G
Published: May 2021

Background

Pregnant women with active perianal Crohn’s disease (CD), have an indication for a caesarean section according to the current ECCO guidelines. This advice is based on the assumption that vaginal delivery leads to exacerbation of perianal disease and to worsening of faecal continence. However, there is no strong evidence to support this. This study aims to examine the effects of delivery method on perianal disease progression and faecal incontinence in women with perianal CD

Methods

In this retrospective cohort study, 209 women were selected from a large IBD database within a tertiary hospital in the Netherlands. All women are aged >18 years, have perianal CD, and have at least one child. In addition, 102 women of this cohort completed a questionnaire. Faecal continence was scored using the Vaizey-score. Descriptive analysis using SPSS and linear regression analysis were performed. The outcome was corrected for the years after delivery (median 15, range 0-55). p-values <0,05 were considered statistically significant.

Results

The caesarean section rate within this cohort was 27,8%, which is high when compared the general Dutch population (14%). Within the group of women who delivered at least one child vaginally (n=84), 25,5% reported an alteration of faecal continence, compared to 18,8% of the women who never had a vaginal delivery (n=18). No significant relation between mode of delivery and faecal continence was found (B 0,97 [-1,19-3,14] p 0,375). The average Vaizey-score within this cohort in women who delivered solely through caesarean section had a median Vaizey-score of 5 (range 0-12). Women who had at least one vaginal delivery had an median Vaizey-score of 7 (range 0-20). In a large study amongst the general Dutch population (n=1259) a median Vaizey-score of 11 (range 0-17) was reported.

Conclusion

Faecal incontinence after vaginal delivery in CD women with perianal fistula is not significantly increased. Therefore the current guideline to advice a caesarean section should be adjusted and other factors such as the location of the fistula should be taken into account. To draw solid conclusions, better registration of fistula location and objective documentation of fistula activity (using PDAI-score) and stool consistency is needed.