bluuebunny/crossref_metadata_2025 huggingface dataset:
P750 Biosimilar Infliximab Switching is Not Associated with Adverse Outcomes: A Real-World Effectiveness Analyses in a National U.S. Cohort of U.S. Military Veterans with Inflammatory Bowel Disease
Authors: Hou J K , Pham C , Sansgiry S , Modi V , Waljee A K
Published: January 2023

Background

Infliximab (IFX) biosimilars are widely available for Crohn’s disease (CD) and ulcerative colitis (UC). However, implementation of biosimilar switching has been highly variable in the U.S. Barriers to switching include patient and provider concerns of lower efficacy, immunogenicity, and safety. Biosimilar switching in Veterans Affairs (VA) was based on local facility policy rather than patient/provider selection and thus less prone to selection bias. The goal of this study is to evaluate the safety and effectiveness of biosimilar switching in a National U.S. Cohort of Veterans with CD and UC.

Methods

We conducted a retrospective cohort study of CD and UC patients who received maintenance originator IFX from 2017-2019 in the VA. CD and UC patients were identified using a previously validated algorithm and confirmed by chart review. Patents on maintenance IFX originator were identified by dispensed medication from Corporate Data Warehouse (CDW). Patients switched to IFX biosimilar after 2017 were identified in CDW by dispensed medication and confirmed by chart review. Adverse outcomes were defined as infusion reaction, serious infection (intravenous antibiotic, delay of IFX), immunogenicity (anti-IFX antibody or IFX escalation) or disease flare (escalation of steroid, IBD related Emergency department visit, hospitalization) confirmed by chart review. Adverse event rates at 12 months for patients continued on originator IFX were compared to patients switched to IFX biosimilar using univariate and multivariate logistic regression models adjusting for patient and non-patient factors.

Results

A total of 790 patients (492 CD, 298 UC) on originator IFX were identified during the study period. Of these, 380 patients were identified to have switched to IFX biosimilar and 410 patients continued on IFX originator during the study period. Overall adverse outcomes occurred in 35.6% of patients at 12 months (35.6% switch, 35.3% non-switch, p=0.87). No statistically significant difference in rates of infusion reaction, serious reaction, immunogenicity, or IBD flare were identified between switch and non-switch groups. In multivariate logistic regression including age, race, gender, concomitant medication, and VA priority status, no significant differences in adverse outcomes at 12 months were observed between switch and non-switch groups (aOR 1.09, 95% CI 0.76-1.42).

Conclusion

In a real-world national U.S. cohort of patients with CD and UC, we observed IFX biosimilar switching was not associated with adverse events compared to continuation on IFX originator. While this study may be underpowered to detect such a small difference, these findings provide further reassurance that IFX biosimilar switching for CD and UC is safe and effective.
P751 Crohn’s Disease Exclusion Diet: A single centre real-life experience
Authors: Lababidi N E , Pavel F
Published: January 2023

Background

According to ECCO-ESPGHAN consensus guidelines, exclusive enteral nutrition (EEN) is the first line therapy for induction of remission in children with active luminal Crohn’s disease (CD). Steroids may be considered in cases when EEN is not an option. However, adherence to EEN is not ideal. According to various sources it ranges from 50-91 %. This poor adherence is mainly due to palatability and monotony. Many attempts have been made to find an alternative to EEN. One of them is Crohn’s Disease Exclusion Diet (CDED) with partial enteral nutrition (PEN), which shows promising results in efficacy, safety, and adherence. This study evaluates the efficacy of CDED with PEN in a single European centre.

Methods

Retrospective evaluation of prospectively collected dated of children treated with CDED with PEN between 10/19-11/22. Wellbeing, anthropometric data, and laboratory results were evaluated prior to the commencement of CDED with PEN and at the end of both phases 1 and 2. A mean, median and a standard deviation were calculated were applicable. ANOVA was used for evaluation of presence of statistically significant differences and a P-value ≤ 0.05 was regarded as such.

Results

CDED with PEN was used in 24 patients. The mean age at diagnosis was 14.6±3.7 years. At the time of evaluation, 21/24 patients have completed phase 1 and 20/24 have completed phase 2. Three patients were still in phase 1 and 1 in phase 2. One patient decided to quit CDED with PEN at the end of phase 1 and 2 more at the end of phase 2. All patients, who started phase 1 completed it, and 95.2% completed phase 2. Non-adherence was recorded in two patients: once in diet composition and twice in PEN volume.

At commencement of CDED with PEN, dietary intervention was the only treatment in 16/24 patients. Three patients were on Azathioprine (AZA), 2 5-aminosalicylic acid (5-ASA), 1 Methotrexate (MTX) and another Prednisone. At the end of phase 1, 8 patients were on anti-TNF-α, 8 were using AZA, 2 5-ASA and 1 MTX. At the end of the phase 2, anti-TNF-α was used in 12 patients, AZA in 8, MTX in 3 and both anti-IL12/23 and 5-ASA in 1 patient.

CRP and ESR showed a statistically significant decrease (P< 0.01) at the end of phases 1 and 2, Faecal calprotectin (FC) showed so at the end of phase 2 (P< 0.01). Other followed parameters failed to show a significant difference at the end of follow-up.

Conclusion

These data support that CDED with PEN is both well tolerated and has a very high adherence rate. They also confirm that CRP and ESR decrease significantly at the end of both phases and FC at the end of phase 2. CDED with PEN should be considered as an alternative to EEN and steroids in induction of remission of luminal CD in children.
P756 Cumulative adverse events of anti-TNF therapy in IBD patients at a large tertiary centre – a 13-year real-world experience
Authors: Majumder S , Love M , Davis J , Sharma N , Nabil Quraishi M , Cooney R , Ghosh S , Iacucci M , N Shivaji U
Published: January 2023

Background

Anti-TNFα is the first class of biologics approved for treatment of moderate-to-severely active Inflammatory Bowel Disease (IBD). More than two decades on, anti-TNFs remain one of the most commonly used biologics for both Ulcerative Colitis (UC) and Crohn’s Disease (CD), and often as first-line therapy. Although effective, they cause several adverse events (AEs), sometimes requiring withdrawal of therapy. The aim of the study was to record cumulative AEs in IBD patients and report on real-world safety profile of this class of drugs.

Methods

All IBD patients exposed to anti-TNF therapy were identified from EMR at two centres of a large tertiary referral centre between January 2009 and June 2022. All relevant demographic and clinical data were collected for those patients with well recorded AEs and follow-up. Data on cumulative AEs directly attributed to anti-TNFs that ranged from mild reactions to serious AEs (defined as those requiring review/withdrawal of anti-TNF), were collected. Data on malignancies in this cohort was collected separately. The data were analysed and statistical analysis carried out using the IBM® SPSS® Statistics software package Version: 28.0.0.0.

Results

Total of 844 patients (M=408, 48%; median age 37years) were included, of which 61% were Caucasian. Majority had CD (608;72%) with mean age at diagnosis of 27y (SD 15y) and a median disease duration of 12years. About 50% of patients were on monotherapy and adalimumab was most frequently used (52%). A significant proportion of patients (44%) discontinued therapy during the follow-up period covered by the study (median duration 5years); infliximab showed best persistence rate (Fig 1). The commonest AEs were dermatological followed by auto-immune. Infections affected all age groups and bacterial infections were most common. Male sex, age groups of 18-50 years were statistically more likely to develop an AE (Table 1). 16 malignancies and 1 death were recorded in this cohort.

Conclusion

In our cohort, a significant number of AEs to anti-TNFs were noted, frequently resulting in the withdrawal of therapy. Although effective, anti-TNFs related AEs lead to poor persistence rates and contribute to increased risk of infections, particularly in >60y age group. Clinicians must be aware of the wide range of AEs due to anti-TNFs; these risks must be considered, and patients selected carefully to maximize success. With a wider choice of biologics and small molecules currently available, other options with apparently more favourable safety profiles could be considered earlier in the treatment algorithm.
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

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 < 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

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

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 (>3mg/ml) with detectable anti-drug antibodies (ADA) (>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 (>40 AU/ml) compared to low. Variables that significantly affected clinical decisions were IFX dose (p<0.001), IFX interval (p=0.004), and clinical disease activity (p<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

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

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 (< 20mm, >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

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 > 150; UC was considered active when TMS >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

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 >5mg/ml, undetectable anti-drug antibodies (ADA) (<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 >5mg/ml and undetectable ADAs; of these 160 (54%) had been on CT for >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

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 <100% EN. A ratio of isobutyrate (IC4) to C2> 0.039 and a ratio of IC4 to C2+C4> 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> 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.
P808 Risk of relapse after vedolizumab withdrawal in Inflammatory Bowel Disease for patients in histological remission
Authors: Blad W , Whitley L , Harrow P
Published: January 2023

Background

A key clinical question is whether we should be withdrawing advanced inflammatory bowel disease (IBD) medications after a period of sustained remission. There is data to suggest that risk of relapse on withdrawal of vedolizumab is higher than that of anti-TNF therapy1. Drug costs are still considerable and so withdrawal of medications will also have significant financial benefits.

The aim was to review the outcomes of vedolizumab withdrawal in patients in remission, in particular for those where a clinical decision was made following confirmed histological remission of their IBD

Methods

This was a single-centre retrospective review of patients in the IBD clinic at a tertiary referral centre in London. We analysed all those who had stopped vedolizumab at least six months prior and were in either clinical, biochemical, radiological, endoscopic or histological remission. We assessed for evidence of a flare of disease following withdrawal of vedolizumab and the need of further biological treatment.

Results

38 patients had vedolizumab withdrawal for remission with a median length of treatment of 36 months. 28 (74%) had a flare up of disease requiring medication change with 24 (63%) requiring biologics. 21 restarted vedolizumab and 79% responded to this medication. Importantly, 5 patients are still less than a year since stopping and so still at high risk of relapse.

Of the 21 patients confirmed to be in histological remission, 17 (81%) had a flare of disease requiring further treatment, of which 15 (71%) required biologics. Median time to flare was 7 months with only two patients flaring after a year of cessation. All 15 were started on vedolizumab and 12 (80%) responded to this but one had a subsequent early secondary loss of response. Of those who did not respond to vedolizumab, one required emergency surgery, one responded to ustekinumab and one only has partial response to a third biologic.

Conclusion

Relapse following vedolizumab withdrawal occurs in a significant number of patients even when they have been in remission for a long period of time. It usually occurs quickly within the first year and having confirmed histological remission does not seem influence this risk. Recapture of response is reasonably good and occurs in four fifths of patients. Despite the significant cost savings of stopping vedolizumab, clinicians need to consider the risk to benefit ratio of stopping when relapse is such a common event.

1 Martin, A., Nachury, M., Peyrin-Biroulet, L., et al, GETAID-Vedo-STOP Study Group (2020). Maintenance of Remission Among Patients With Inflammatory Bowel Disease After Vedolizumab Discontinuation: A Multicentre Cohort Study. Journal of Crohn's & colitis, 14(7), 896–903. https://doi.org/10.1093/ecco-jcc/jjaa005
P809 The impact of different treatment strategies in newly diagnosed patients with Crohn’s Disease: a multicentre study
Authors: Revés J , Morão B , Montanaro G , Sciberras N , Bravo A C , Glória L , Ellul P , Torres J
Published: January 2023

Background

The early use of effective therapy may change outcomes in patients with Crohn’s disease (CD). The aim of this study was to compare three different treatment strategies in CD (“top-down”, “accelerated step-up” and “regular step-up” therapy).

Methods

This was a retrospective multicentre study including patients with incident CD between 2009-2021. Patients were categorized into 3 treatment groups: group 1) “top-down”: anti-TNF ± immunomodulator (IM) within the first year of diagnosis with a maximum interval of 6 months between both drugs; group 2) “accelerated step-up”: IM within the first year of diagnosis followed by anti-TNF 6-12 months later, and group 3) “regular step-up”: IM within the first year of diagnosis with or without the need to further escalate to biologic (>12 months after the beginning of IM). The primary outcome was endoscopic healing (EH; SES-CD<3 and no ulcers) at the end of the follow-up; secondary outcomes were CD-related intestinal resection and hospitalization due to CD-flare. Cox regression analysis was performed and Kaplan-Meier curves were computed for each outcome.

Results

156 patients (54% males) were included, with 46% having ileocolonic disease (L3) and 68% an inflammatory phenotype (B1) at diagnosis. Baseline patients’ characteristics in each different treatment strategy are demonstrated in Table 1. Patients were followed for a median of 69 (44-98) months; 12% in group 1 and 19% in group 2 had to switch biologicals (p=0.4); 64% in group 3 escalated to biologicals with a median time since diagnosis of 30 (20-50) months. In group 1, 73% of the patients used concomitant IM. At the end of follow-up, 50% of all patients achieved EH, 20% needed hospitalization and 13% had a CD-related intestinal resection. In a multivariate model adjusted for gender, age at diagnosis, disease location, disease behaviour, perianal disease, and prior surgery, patients in group 3 had a lower probability of achieving EH when compared with patients in group 1 (HR 0.7, 95%CI 0.5-0.96, p=0.02) and group 2 (HR 0.3, 95%CI 0.1-0.8, p=0.01). Kaplan-Meier curves are demonstrated in Figure 1. Using the same model, no differences were found in terms of hospitalization or need for intestinal surgery. Fistulizing disease was a significant predictor for intestinal surgery (HR 2.4, 95%CI 1.5-3.8, p<0.01).

Conclusion

Introduction of biological therapy within the first two years of diagnosis, either in a “top-down” or “accelerated step-up” approach was associated with a higher probability of achieving EH, as compared to the introduction of an immunomodulator followed by a later introduction of biologic. No differences were found for hospitalization or intestinal surgery. Fistulizing disease was a significant predictor for surgical intervention.
P810 Association between Ustekinumab Trough Levels, Serum IL-22 and Oncostatin M Levels with Clinical and Biochemical Outcomes in Patients With Crohn’s Disease
Authors: Bertin L , Gubbiotti A , Buda A , Zingone F , Savarino E V , Barberio B
Published: January 2023

Background

Ustekinumab is an effective treatment for patients with Crohn’s disease (CD). Strategies to monitor response to therapy may improve clinical control of the disease and reduce economical costs. Therefore, we aimed to evaluate if trough levels (TL) of ustekinumab, serum IL22 and oncostatin M levels could be considered early markers of non-response assessing their correlation with clinical and biochemical outcomes in CD.

Methods

We consecutively recruited patients with CD treated with ustekinumab from October 2018 to September 2020. Clinical and biochemical data were collected at baseline, at weeks 12 and 24. TL were dosed at week 12 and week 24, IL22 levels and oncostatin M serum levels were dosed at baseline and at week 12. A primary analysis determined if TL, IL22 levels and Oncostatin M serum levels were associated with clinical response (reduction in Harvey Bradshaw Index score of at least 3 points), clinical remission (Harvey Bradshaw Index score <5) and biochemical remission (negative C-reactive protein (CRP) or fecal calprotectin levels (FC) <250 μg/g). A Shapiro-Wilk test was conducted to test for normality for all variables and a Mann Whitney test was used to evaluate correlation of TL, IL22 and Oncostatin M serum levels with HBI index variation and biochemical remission.

Results

Among 84 patients enrolled, 10 were excluded because they were lost to follow up or had incomplete data. At week 24, 59.4% of patients had a clinical response and 47.9% were in clinical remission. TL dosed at week 12 significantly correlated with clinical response at week 12 (p=0.047) and at week 24 (p=0.019) and with clinical remission at week 12 (p=0.02) and at week 24 (p=0.02). TL at week 12 also correlated with biochemical remission both at week 12 (CRP and FC normalization, p<0.001 and p=0.04, respectively) and at week 24 (CRP and FC normalization, both p=0.01). At week 24, patients with positive FC had higher median trough concentrations of ustekinumab than those with negative FC (p=0.01). Oncostatin M levels at baseline significantly correlated with FC levels at week 12 (p<0.001) and at week 24 (p=0.04), but did not correlate with clinical remission. IL22 levels at baseline were lower in patients in clinical and biochemical remission at week 24, although these trends did not reach statistical significance (p=0.43 and p=0.86).

Conclusion

Ustekinumab was an effective therapy in patients with CD. TL at week 12 were predictive of both clinical and biochemical remission at week 12 and 24. Oncostatin M levels at baseline significantly correlated with FC levels at week 12 and 24.
P812 Fluorescently labelled vedolizumab identified macroscopic and microscopic mucosal drug distribution in patients with inflammatory bowel disease
Authors: Van Der Waaij A , Gabriëls R , Linssen M , Volkmer P , Robinson D , Hermoso M , Karrenbeld A , Festen E , Dijkstra G , Kats-Urgulu G , Nagengast W
Published: January 2023

Background

Biological treatment in inflammatory bowel disease (IBD) patients is currently hampered by high non-response rates. To enhance personalized medicine and predict response to biological therapeutics such as vedolizumab, the working mechanism should be elucidated. We aimed to visualize macroscopic and microscopic vedolizumab distribution and detect drug target cells during quantified fluorescence molecular endoscopy (QFME) to improve understanding of the mechanism of action.

Methods

Vedolizumab-800CW was developed and GMP produced. Forty-three QFME procedures were performed in thirty-seven IBD patients two to four days after intravenous administration of vedolizumab-800CW. Each QFME procedure consisted out of endoscopic assessment of the inflammation status per colonic segment by high-definition white light endoscopy, followed by real-time in vivo assessment of the macro-distribution of fluorescent vedolizumab-800CW signal and quantification by spectroscopy of selected segments. Dose escalation was performed using 0.0 mg, 4.5 mg and 15 mg. Subsequently, two patient cohorts were added that received a dose of 75 mg or 300 mg unlabelled vedolizumab prior to vedolizumab-800CW to assess target saturation. Tissue biopsies were obtained for histopathological assessment, for further ex vivo analysis of the fluorescent signal and for visualization of the microscopic distribution and identification of vedolizumab-800CW target cells by fluorescence microscopy (fig 1).

Results

Both during in vivo QFME and ex vivo analysis a clear dose- and inflammation severity-dependent increase of the fluorescent drug signal was revealed (fig 2). A significant difference was found between the dose groups for non-inflamed (p=0.0004), mild inflamed (p=0.0397) and severe inflamed (p=0.0056) tissue. In addition, the difference in intrinsic fluorescence between the severe inflamed tissue and non-inflamed tissue was significant within the 15 mg (p<0.0001), 75 mg + 15 mg (p=0.0118) and the therapy + 15 mg group (p=0.0005). Fluorescence microscopy revealed clear membrane binding of vedolizumab-800CW to inflammatory cells and migration into the inflamed mucosa. Additional analyses to identify specific target cells are ongoing and immune compositions of regions with high and low vedolizumab signal will be unravelled.

Conclusion

QFME using vedolizumab-800CW elucidated novel detailed macroscopic and microscopic vedolizumab distribution in the inflamed target organ. In addition, its shows the potential of QFME to better understand local drug distribution, target cell identification and target engagement, which could improve understanding of targeted drugs over standard pharmacokinetic and pharmacodynamic analysis.
P823 Biologic Penetration, hospitalization rates and need for major abdominal surgery in inflammatory bowel diseases: a comparative observational study between pediatric and adult patients
Authors: Silva A C V , Tumelero T J , Magro D O , Yamamoto D R , Ribeiro L B M , da Silva G S , Truppel S K , Vieira M C , Kotze P G
Published: January 2023

Background

There is lack of epidemiological data in regard to the accurate situation of Inflammatory Bowel Disease (IBD): Crohn’s disease (CD) and ulcerative colitis (UC) in Brazil. It is known that both diseases' progression is variable and the chronic iinflammation results in structural bowel damage. Comparative data between adult and pediatric patients in the IBD field, regarding different outcomes, is lacking globally. We aimed to analyze the proportion of use of biologicals, need for major abdominal surgery and hospitalizations in CD and UC , between adult and pediatric patients.

Methods

Cross-sectional and multicenter study. Data was collected from all consecutive IBD patients seen as outpatients or admitted to hospital, from 2015 – 2021, in two IBD tertiary centers from a capital from south Brazil. We included all patients with clinical, endoscopic, radiological or histological diagnosis of CD and UC. Patients with unclassified colitis or without available data in medical records for investigating variables of interest were excluded. Patients were classified in two main groups (CD and UC) and in two subgroups each, according to age range: adults and pediatrics. Analyses were made by frequency, proportion, Fisher’s exact test and Chi-squared test, through software IBM SPSS Statistics 28.

Results

Eight hundred and twenty-nine patients were included: 509 with CD (378 adults/131 pediatrics) and 320 with UC (225/95). There was significantly difference between diseases in the proportion of biological use 75.0% in CD and 31.6% in UC (p<0.001), surgeries 49.7%/14,1% (p<0.001) and hospitalizations 58.9%/30.9% (p<0.001), respectively. In CD, there was no difference regarding biological use (80.2% in pediatric group vs. 73.3% in adults; p=0.129), surgeries (46.6% vs. 50.8%; p=0.419) and hospitalizations (64.9% vs. 56.9%; p=0.122). There was significantly difference in biological use (40.0% vs. 28.0%; p=0.048) and hospitalizations (47.4% vs. 24.0%; p< 0.001) in UC and there was no difference regarding surgery necessity between age ranges (17.9% vs. 12.4%; p=0.219).

Conclusion

There was a higher proportion of biological use, surgery and need for hospitalizations in CD as compared to UC. Comparing age ranges, pediatric patients with UC used more biologicals and required more hospitalizations than adults, but there was no difference in the need for abdominal surgery. In CD, there was no significant difference in the three main outcomes, between the age groups.
P825 The course of inflammatory bowel disease in setting of liver transplantation
Authors: Filipec Kanizaj T
Published: January 2023

Background

Liver transplantation (LT) remains the only therapeutic option for patients with primary sclerosing cholangitis (PSC) who develop biliary tract complications or cirrhosis. Around 50-80% of PSC patients have IBD which represent phenotypically unique disease. Patients are prone to negative effects of complications of liver disease and immunosuppression, unpredictable course of both diseases and development of neoplasia. Patients are treated according to standard guidelines related to overall IBD population.

Methods

The study evaluates the IBD course and effects of therapy in PSC transplanted patients. In a period of 2005-October 2022 1453 patients had LT performed at University hospital Merkur, Zagreb, Croatia. 70 (4.8%) of them refers to complications of PSC. 46 (66%) of PSC patients were diagnosed with IBD, majority 43 (93.5%) before LT.

Results

As expected 36 (78.3%) had ulcerative colitis (UC) while 9 (19.6%) Crohns disease. 31 (70%) were males, median age 35 years (IQR 28-47). 35 (76.1%) patients had no IBD activity at LT, whereas 11 (23.9%) had continuously active IBD in follow up. 18 (51.4%) patients with remission at LT developed relapse (median time 536 days, IQR 371-1234) whereas other 17 (48.6%) have stable remission.

Nine (19.6%) patients had malignant disease, 3 (6,5%) cholangiocelular carcinoma in explanted liver, 5 (10,9%) colorectal cancer (CRC) and 1 both tumors.

Before LT 24 (52.2%) patients had no specific IBD treatment, whereas 8 (33.3%) were treated with aminosalicilates (AsA), 5 (10.9%) azathioprine (AzA), 6 (13.1%) glucocorticoids (GK) and 3 (6.5%) biologics.

After LT 23 (50%) are treated with ASA, 12 (26.1%) AzA and 11 (23.9%) biological therapy (36.4% anti-TNF, 27,3% vedolizumab and 36,4% on multiple biologics). AsA as monotherapy is successful in 63.6% of treated patients, AzA in 50% and biologic therapy 27.3%, respectfully. Even though it did not reach statistical significance, more patients with relapse of IBD after LT are treated with AzA than in group of continuously active disease (33.3 vrs 9.1%) while this is opposite for biologic therapy (27.8 vrs 54.5%).

8 (17.4%) patients were treated with total colectomy, 2 before, 3 during and 3 after LT, 6 due to CRC and 2 intractable IBD.

Regrading immunosuppression 42 (91.3%) are treated with tacrolimus, 4 (8.7%) with cyclosporine, 24 (52.2%) with mycophenolate mofetil and 11 (23.9%) prolonged GK.

Conclusion

Management of IBD in the context of PSC and LT setting is a major clinical challenge and specific guidelines are urgently needed. Since the effectiveness of standard therapy is possibly weaker with a high risk of cancer it is necessary to consider an earlier approach to colectomy.