bluuebunny/crossref_metadata_2025_split huggingface dataset:
P757 Visceral adiposity and not subcutaneous adiposity or body mass index is more strongly associated with relapse in inflammatory bowel disease
Authors: Tan J , Shadbolt B , Jain T , Subramaniam K 
Published: January 2023

Abstract

Background
The role of body composition in inflammatory bowel disease (IBD) has still not been established due to heterogenous evidence. This study aimed to assess if abdominal body composition parameters were associated with outcomes in inflammatory bowel disease.

Methods
In this retrospective study abdominal body composition was evaluated using routinely acquired computed tomography (CT) from eligible patients with IBD between January 2014 and September 2021. Cross sectional areas of total fat (TFA), subcutaneous fat (SFA), visceral fat (VFA) and skeletal muscle (SMA) including their indices and ratios were measured at lumbar 3 (L3) vertebrae level using appropriate software. The outcome measure was relapse defined as acute flaring of symptoms and/or worsening biochemical markers, endoscopic recurrence requiring dose intensification of current therapy and surgical resection. Spearman’s correlations between body composition parameters were analysed. Binary logistic regression adjusting for demographics, smoking, disease characteristics (type, duration, location, behaviour) and medications was used to test for the relative significance of SFA, VFA, SMA and body mass index (BMI) on the outcome measures. A forward logarithmic likelihood method was used to test for it.

Results
Fifty-three IBD patients (58% male; 42% female) with 22 (42%) in relapse were included for abdominal CT analysis. Mean age of patients with relapse was 41.8 ± 16.2 years while those without relapse was 48.4 ± 12.5 years (p = 0.360). Mean BMI of patients with relapse was 25.6 ± 4.4 while those without relapse was 28.1 ± 7.0 (p = 0.457). Mean disease duration of patients with relapse was 15.3 ± 9.2 years while those without relapse was 21.3 ± 10.7 years (p = 0.583) [see Table 1]. Mean VFA was not significantly lower in relapse than remission (mean: 95.3 ± 99.5 cm² vs 119.7 ± 89.6 cm²; logarithmic p = 0.222), whereas mean SFA was significantly higher in relapse than remission (mean: 129.0 ± 64.3 cm² vs 225.3 ± 156.8 cm²; logarithmic p = 0.016) [see Table 2]. VFA and BMI correlated strongly with all other body composition parameters according to Spearman’s model (p &lt; 0.001) [see Table 3]. After performing binary logistic regression and accounting for variables including age, gender, smoking status, type of IBD, disease characteristics (duration, location, behaviour), corticosteroid use, biologic therapy, anti-TNF level, VFA (p = 0.013) was significantly associated with relapse in comparison to SFA (p = 0.063) and BMI (p = 0.563).

Conclusion
Visceral adiposity and not BMI or subcutaneous adiposity is more strongly associated with relapse in IBD.
P762 Population Pharmacokinetic Model of Intravenous Infliximab in Korean Patients with Crohn’s Disease
Authors: Seo J , Lee M H , Hong H , Oh E H , Hwang S W , Park S H , Yang D H , Byeon J S , Myung S J , Yang S K , Bae K S , Ye B D 
Published: January 2023

Abstract

Background
Infliximab (IFX), a monoclonal antibody approved for treating Crohn’s disease (CD), is known to show differing drug clearances in patients according to several clinical factors. However, information on the population pharmacokinetics (PKs) of intravenous (IV) IFX is lacking for Korean patients with CD. Therefore, in this study, we aimed to establish a PK model of IV IFX for this population.

Methods
We retrospectively analyzed data of CD patients treated with IV IFX at Asan Medical Center, a tertiary university hospital, from April 2019 to March 2022. Serum trough IFX concentration, clinical laboratory values, Crohn’s disease activity index, and demographic data were collected. NONMEM® version 7.5 was used for nonlinear mixed effects modeling.

Results
Of the one hundred patients included for analysis in this study, 72 were male (72.0%) (Table 1). No patient had detectable antibodies to IFX. [SJ1] A total of 823 serum IFX concentration data were collected and analyzed for fitting according to the minimization of objective function value and weighted residuals. As a result, a one-compartment population PK model with first-order elimination best described the serum trough IFX concentration measurements. Population PK estimates were 0.012 L/h for clearance (CL) (95% confidence interval: 0.012–0.013) and 6.301 L for the volume of distribution (V) (95% confidence interval: 5.932–6.671) (Table 2). Covariate analysis showed that CL and V increased as body weight increased. CL was higher in patients with low serum albumin, high serum C-reactive protein, and older age, with differing coefficients for each covariate (Figure 1). The final covariate model predicted the observed concentration-time profiles of IFX reasonably well (Figure 2).

Conclusion
We established a population PK model of IV IFX for CD patients in Korea. The final covariate model showed that the CL of IFX was affected by serum albumin and C-reactive protein levels, in addition to body weight and age.
P765 Tolerating infliximab therapeutic drug monitoring without anti-drug antibodies – an argument for drug intolerant assays?
Authors: Carlson S , Evgeniou V , Kok K 
Published: January 2023

Abstract

Background
Therapeutic drug monitoring (TDM) helps guide clinical decision making in IBD patients on infliximab (IFX). There are two types of IFX TDM assays, drug tolerant and intolerant, where drug tolerant assays allow the detection of anti-drug antibodies (ADA) in the presence of drug and the latter does not. Our immunology laboratory is in the process of changing from a drug tolerant to a drug intolerant IFX assay for cost reasons. We aimed to determine whether this switch would affect the management of IBD patients with therapeutic IFX levels and detectable antibodies.

Methods
This was a retrospective cross-sectional study in a central London tertiary hospital. Patients were included if they had a diagnosis of Crohn’s Disease (CD), Ulcerative Colitis (UC), or Indeterminate colitis, and had therapeutic IFX levels (&gt;3mg/ml) with detectable anti-drug antibodies (ADA) (&gt;10 AU/ml) between January 2017 to March 2022. Electronic health records were reviewed to determine clinical actions within 4 months of drug measurement. Actions were categorized into three groups by two gastroenterology physicians: no change to management, ADA dependent or independent actions. ADA dependent decisions were immunomodulator (IMM) addition or discontinuation. ADA independent decisions included switching biologic, stopping IFX, or escalation/de-escalation in IFX dosing.

Results
A total of 2675 IFX TDM tests were performed for IBD patients in the defined period. Of these, 237 patients had 477 TDM results with therapeutic IFX levels and detectable ADA. Baseline characteristics were 36.8% (n=87) female, mean age (y) of 30 (SD ±13), and 66.2% (n=157) had CD. At the time of measurement, 76.1% (n=363/477) of patients were on combination therapy with an IMM and 23.1% (n=110) had active disease on physicians’ global assessment. Changes to management were made in 23.5% (112/477) of clinics following TDM, but only 2.5% (12/477) of actions were ADA dependent. There was no difference in high titer ADA group (&gt;40 AU/ml) compared to low. Variables that significantly affected clinical decisions were IFX dose (p&lt;0.001), IFX interval (p=0.004), and clinical disease activity (p&lt;0.001).

Conclusion
1 in 40 clinical decisions made in patients with therapeutic drug levels and detectable ADAs rely on knowing the ADA level. A cost analysis, with an appropriate IFX drug level threshold under which ADAs would be performed, assessing the proposed switch to a drug intolerant TDM assay would help determine whether cost savings outweigh missed decision-making opportunities.
P770 Autologous regulatory T cell transfer in patients with refractory ulcerative colitis: Interim report of a phase 1, dose-escalation trial
Authors: Voskens C , Stoica D , Rosenberg M , Weidinger C , Vitali F , Zundler S , Ganslmayer M , Wiesinger M , Wunder J , Kummer M , Siegmund B , Schnoy E , Rath T , Hartmann A , Hackstein H , Schuler-Thurner B , Berking C , Schuler G , Atreya R , Neurath M F 
Published: January 2023

Abstract

Background
Ulcerative colitis (UC) is marked by impaired mucosal homeostasis with predominance of intestinal effector T cells and insufficient expansion of mucosal regulatory T cells (Tregs), thereby providing a scientific rationale for Treg-based immunotherapy in UC.

Methods
We developed a protocol to generate large numbers of autologous CD25+ cells under aegis of IL-2, rapamycin and anti-CD3/anti-CD28 expander beads ex vivo from CD25+ precursors derived from peripheral blood cells, intended for clinical use under good manufacturing practice (GMP) conditions. We initiated a single-centre, open-label, fast-track dose-escalation, phase-1 clinical trial with a single adoptive transfer of autologous ex vivo expanded CD4+CD25+CD127−/lo Tregs in patients with refractory UC. The primary objective of the trial was to define safety and the maximum tolerable dose of a single intravenous administration of autologous expanded Tregs according to the fast-track dosing principle. Adoptive transfer was escalated from the starting dose of 0.5×106 Tregs/kg body weight to the next dose level (1×106, 2×106, 5×106 and 10×106 Tregs/kg body weight) in each consecutive patient, respectively, if no dose-limiting toxicity occurred. We here report interim study data of the first 8 patients that received Treg transfer and were followed up over 12 weeks. There were no changes in concomitant medication during the study period.

Results
The 8 patients received 0.5 x106 (n=1), 1×106 (n=1), 2×106 (n=1), 2.8x106 (n=1), 5×106 (n=1) and 10×106 (n=3) Treg/kg body weight, respectively. The patients did not show any dose-limiting toxicity and there were no adverse events related to Treg transfer. 87.5% (7/8) of patients had previously received treatment with at least 2 different substance classes of advanced therapies, such as biologics and JAK inhibitors and the mean Mayo Score (MS) at baseline was 9.1±1.6. The mean modified MS (mMS) dropped significantly from 6.6±1.2 at baseline to 4.5±2.2 at week 4 (p=0.006) and 4.6±2.0 at week 12 (p=0.01). There was reduction of mean faecal Calprotectin levels from 1708±397 µg/g at baseline, to 1411±471 µg/g at week 4 and 919±332 µg/g at week 12. Clinical response was reached by 62.5% (5/8) of patients at week 4 and also week 12. Clinical response predominantly occurred in patients receiving the highest number of 10×106 Tregs/kg body weight. Clinical remission was achieved by 12.5% (1/8) of patients at week 4 and also week 12.

Conclusion
Autologous regulatory T cell transfer was well tolerated up to the maximal tested dose of 10×106 Tregs/kg body weight. Study results suggest that adoptively transferred polyclonal Tregs might be effective in refractory ulcerative colitis, warranting further clinical studies.
P788 Endoscopic management of patients with high-risk colorectal colitis-associated neoplasia: a Delphi study
Authors: Bak M , Albéniz E , East J , Coelho-Prabhu N , Suzuki N , Saito Y , Matsumoto T , Banerjee R , Kaminski M , Kiesslich R , Coron E , de Vries A , van der Woude C J , Bisschops R , Hart A , Itzkowitz S , Pioche M , Moons L , Oldenburg B 
Published: January 2023

Abstract

Background
Current guidelines recommend endoscopic resection of visible and endoscopically resectable colorectal colitis-associated neoplasia (CAN) in patients with inflammatory bowel disease (IBD). However, patients with high risk CAN are often not amenable to conventional resections techniques and a consensus approach for the endoscopic management of these lesions is presently lacking. This Delphi study aims to reach consensus amongst experts on the endoscopic management of these lesions.

Methods
A three-round modified Delphi process was conducted to reach consensus amongst worldwide IBD and/or endoscopy experts (n=18) from three continents. Experts were chosen based on the extensive clinical experience with IBD and/or EMR/ESD in patients with IBD, and the authorship on multiple peer-reviewed publications on CAN, the endoscopic resection of CAN and/or EMR/ESD. Consensus was considered if ≥ 75% agreed or disagreed. Quality of evidence was assessed by the criteria of the Cochrane Collaboration group.

Results
Consensus was reached on all statements (n=14). Experts agreed on a definition for CAN and high-risk CAN (HR-CAN). Consensus was reached on the examination of the colon with enhanced endoscopic imaging prior to resection, the endoscopic resectability of a HR-CAN lesion and endoscopic assessment and standard report of CAN lesions. In addition, experts agreed on type of resections of HR-CAN (&lt; 20mm, &gt;20 mm, with or without good lifting), endoscopic success (technical success and outcomes), histologic assessment and follow-up in HR-CAN.

Conclusion
This is the first step in developing international consensus-based recommendations for endoscopic management of (HR-)CAN. Although the quality of available evidence was considered low, consensus was reached on several aspects of the management of (HR-)CAN. The present work and proposed standardization might benefit future studies.
P795 Impact of anxiety and depression on inflammatory bowel disease patients
Authors: Sina Dr. M , Pemaj X , Djegsi A , Telaku* S , Osmanaj D , Babameto A , Prifti S 
Published: January 2023

Abstract

Background
IBD patients may complain of stress and emotional disorders (anxiety and depression), impacting their quality of life. Anxiety and depression has been reported to be more common in IBD than in the general population. The aim of study was to estimate the prevalence and severity of anxiety and depression among IBD patients and to identify their impact on IBD related features.

Methods
Consecutive IBD patients presented from January 2021 to February 2022 at our outpatient IBD clinic, were included in this study. Demographic data, disease activity scores, endoscopic scores, disease duration, localization, hospitalization, laboratory data, were collected for each patient. Based on Hospital Anxiety and Depression Scale (HADS) patients were divided in 2 groups: those with symptoms of anxiety and depression and those without. Total Mayo Score (TMS) was used to evaluate UC disease activity while Crohn’s disease activity index (CDAI) for CD patients. CD was considered active when CDAI score &gt; 150; UC was considered active when TMS &gt;2.

Results
A total of 48 IBD patients (30F: 18M), mean age 41.2±15.6 years were included. 43 (89.6%) patients were diagnosed with UC, and 5 (10.4%) with CD. Mean disease duration was 5.1±4.6 years.37.2% of UC patients were in remission, 20.9% had mild disease, 32.6% moderate, and 9.3% severe disease.40% of CD patients were in remission while 60% had active disease.27.1% of patients were anti TNF-α naïve,43.8% on cortisone, 45.8% were on adalimumab and 27.1% on infliximab treatment.
Anxiety and depression symptoms were present in 45.8% and 27.1% of patients, respectively.These symptoms were found combinedin 27%of the patients. No statistically significant difference was observed on the presence and scores of anxiety and depression between UC and CD patients.Presence of anxiety was significantly associated with female gender (p=0.052), UC disease extent (p=0.078), cortisone use (p=0.077), and previous hospitalizations (p=0.01.8). A significant correlation was observed between anxiety score and CDAI score (p=0.006, r=0.971); UC Mayo score (p=0.013, r=0.376) and CRP level (p=0.053, r=0.281). Presence of depression was associated with female gender (p=0.052) and UC disease activity (p=0.097).Depression score was only associated with UC Mayo score (p=0.062). On multiple linear regression,only TMS was correlated to anxiety and depression score (p=0.022, p=0.048, respectively).

Conclusion
Anxiety and depression are disorders frequently encountered in IBD patients, especially among females. When anxiety and/or depression were present, IBD patients demonstrated a more active disease. Addressing these psychological problems would be helpful achieving a better treatment and quality of life.
P799 Infliximab and immunomodulator combination therapy in inflammatory bowel disease – no longer inseparable?
Authors: Carlson S , Evgeniou V , Kok K 
Published: January 2023

Abstract

Background
The gold-standard for prescribing Infliximab (IFX) in IBD is to use it in combination with an immunomodulator (IMM), thereby reducing the risk of immunogenicity and improving overall outcomes. This practice, however, comes with considerable increased risk of adverse events. There is mounting evidence that withdrawal of IMMs, especially after 6 months of combination therapy (CT), does not reduce IFX trough levels or increase the risk of loss of response (Drobne et al., 2015; Mahmoud et al., 2022). We identified IBD patients on IFX CT who were eligible to stop their IMM based on defined criteria and assessed clinical outcomes of patients who had previously had their IMM withdrawn.

Methods
This was a retrospective cross-sectional study in a central London tertiary hospital. We included patients with a diagnosis of Crohn’s Disease (CD), Ulcerative Colitis, or Indeterminate colitis, with therapeutic IFX levels &gt;5mg/ml, undetectable anti-drug antibodies (ADA) (&lt;10 AU/ml) and at least 6 months of CT from induction between January 2017 and December 2021. Patients were identified on an immunology laboratory database and electronic patient records were manually assessed for baseline characteristics and clinical outcomes. The primary timepoint of interest for clinical outcomes is 4 months after measurement of IFX drug levels.

Results
A total of 825 IBD patients had IFX drug levels performed in the defined time-period. 296 patients had IFX levels &gt;5mg/ml and undetectable ADAs; of these 160 (54%) had been on CT for &gt;6 months. Baseline characteristics were 41.3% (n=66) female, mean age (y) of 29 (SD ±14) and 70.6% (n=113) had CD. In the 4 months after IFX drug assays, 140 of 160 (87.5%) patients remained on CT whereas 20 (12.5%) had previously stopped their IMM. Of those on CT, 90.7% (127/140) were in clinical remission at the time of the assay compared to 90% (18/20) of patients in the IMM withdrawal group (p=0.46). At the time of data collection, 79.3% (111/140) of CT patients remained on IFX therapy compared to 75% (15/20) who withdrew IMMs (p=0.33, median follow up 19 months). IMM withdrawal was predominantly due to side effects (n=16, 80%) with the remainder due to clinical remission (n=4, 20%). The 2/20 (10%) patients with active disease in the IMM withdrawal group were active prior to stopping IMMs.

Conclusion
Patients with good IFX drug levels and undetectable ADAs after at least 6 months of IFX CT did well regardless of whether they withdrew IMMs or not, supporting recent studies that suggest it is safe to do so. Given the number of our patients who could potentially benefit from stopping their IMMs, prospective controlled studies are required to determine whether this is advisable given the theoretical risk of loss of response.
P804 Development and Validation of the Glasgow Exclusive Enteral Nutrition Index of Compliance (GENIE)
Authors: Jatkowska A , White B , Nichols B , Svolos V , Gkikas K , Hansen R , Russell R K , Gaya D , Brownson E , Seenan J P , Milling S , MacDonald J , Gerasimidis K 
Published: January 2023

Abstract

Background
Treatment adherence is key to the efficacy of exclusive enteral nutrition (100% EN) in active Crohn’s disease (CD), but there are currently no biomarkers to objectively support this. We explored faecal parameters as putative biomarkers of compliance with 100% EN, and subsequently developed and validated the Glasgow Exclusive enteral Nutrition Index of compliancE (GENIE).

Methods
Healthy adults replaced all (100% EN) or part (85% EN, 50% EN and 25% EN) of their habitual diet with a polymeric formula (Modulen IBD, Nestle©) for 7 days. Faecal pH, Bristol stool chart score, water content, short chain fatty acids (SCFAs) and branched chain fatty acids (BCFAs) were measured before (D0) and after (D7) each intervention. Faecal biomarkers and threshold values for group assignments were derived using receiver operating characteristic (ROC) curve analyses and machine learning algorithm to develop the GENIE. The GENIE was validated in 30 children with CD, during 100% EN and 4 weeks after return to normal diet.

Results
Sixty-one (31 females) adults (mean age [SD]: 25.9 [4.3] years) were recruited. D7 faecal pH and the ratios of BCFAs to either acetate or butyrate performed the best to differentiate between patients on 100% EN from &lt;100% EN. A ratio of isobutyrate (IC4) to C2&gt; 0.039 and a ratio of IC4 to C2+C4&gt; 0.035 both produced a sensitivity, specificity, and positive predictive value (PPV) of 92%, 83% and 79%, respectively to differentiate between 100% EN vs. all other groups. A faecal pH&gt; 8.0 produced a sensitivity, specificity and PPV of 84%, 86% and 81%, respectively. Findings using machine learning were better than those using ROC curve analysis. Two models were generated; one which includes all faecal metabolites (Laboratory GENIE, L-GENIE), and which produced a sensitivity, specificity and positive predictive value (PPV) of 88%, 94%, and 92%, respectively and a second one (Clinical GENIE, C-GENIE) which considers only faecal pH as the input data and which produced a sensitivity, specificity and PPV of 84%, 86% and 81% (Figure 1). Validation of GENIE models in children with CD found that C-GENIE outperformed L-GENIE, producing a sensitivity, specificity and PPV of 85%, 88% and 88%, respectively (Table 1).

Figure 1: Glasgow Exclusive Enteral Nutrition Index of Compliance.

Table 1: Results of validation of the GENIE model in children with Crohn’s disease (CD) during treatment with 100% EN and after return to unrestricted diet and compared to the development cohort of healthy adults.

Conclusion
GENIE can predict adherence to 100% EN in patients with CD in both the clinical and research settings. It may complement conventional dietary assessment and inform clinical decision, especially in patients who are not in remission.