bluuebunny/crossref_metadata_2025_split huggingface dataset:
P530 Early Intestinal Ultrasound changes to predict treatment response to anti-TNF therapy in paediatric Inflammatory Bowel Disease; a pilot study
Authors: Vos H , Gecse K , D'Haens G , Benninga M , Koot B ,   RAINBOW group
Published: January 2024

Abstract

Background
In paediatric Inflammatory Bowel Disease (IBD) selecting the right treatment in the early stages of disease is key to prevent disease progression and to prevent unnecessary exposure to ineffective treatment. Intestinal ultrasound (IUS) is increasingly used to monitor disease activity in response to therapy. However, little is known about the early transmural changes during anti-tumour necrosis factor (anti-TNF) therapy in paediatric IBD. The aim of this study is to assess the early changes in IUS parameters and to evaluate the very early predictive value of IUS for therapy response in paediatric IBD treated with anti-TNF-α therapy.

Methods
In this pilot study children (aged 3-18 years) starting with anti-TNF therapy (infliximab or adalimumab) were enrolled prospectively if ultrasound at baseline showed bowel wall thickness (BWT) ≥ 2,5mm. IUS was performed at baseline and the most affected bowel segment was identified. Subsequently IUS was repeated in this segment at week 2 and week 13. Response to therapy was determined at week 13.
Response and remission was defined as follows.
- Therapy response: a ≥50% decrease in faecal calprotectin (FCP) in combination with a decrease in PUCAI (≥20 points or normalisation) /PCDAI (≥12.5 points or normalisation), or normalisation of FCP (&lt;250mg/kg))
- IUS response: decrease in BWT by 25% OR decrease in BWT by &gt;2.0 mm of the most severely affected segment compared to baseline
- IUS remission/Transmural healing: BWT&lt;2.0 mm and no Doppler signal(Limberg score) and no mesenteric fat proliferation

Results
Eleven IBD patients (aged 7 to 12 years; 64% female) were enrolled. IUS response was observed in 5/11 patients at week 2 (decrease in BWT -25% in all). Doppler signal decreased in 3/11(one point in Limberg score in all). After 13 weeks 4/11 patients showed therapy response and 3/11 showed IUS remission.

Conclusion
Transmural changes were detected by IUS as early as 2 weeks after initiating anti-TNF therapy. This pilot study observed mainly reactivity in BWT, in contrast with previous studies that initially noted changes in Doppler signal.
IUS has the potential to predict therapy response at an early stage. A larger sample size is needed to accurately assess its predictive value at week 2 for treatment response.
P534 The preference for controlled-release mesalazine formulation of 2 g-granule sachet in patients already experienced 1 g-tablet
Authors: Moon W , Park S J , Kim J H 
Published: January 2024

Abstract

Background
The important factor is a good adherence in the treatment of inflammatory bowel disease (IBD) and the major guidelines recommend that the choice of formulation of mesalazine should consider patient preference and likely adherence. This study was to evaluate the preference for controlled-release (CR) mesalazine 2 g-granule sachet in patients who have been already experienced CR mesalazine 1 g-tablet and its related clinical factors.

Methods
First was treatment with 4 g CR mesalazine a day as two 2 g-granule sachets for 2 weeks in patients with IBD in remission who have already taken 4 g CR mesalazine a day as four 1 g-tablets for more than 3 months in Kosin University Gospel Hospital, Korea. The patients were consecutively enrolled. Second were the patients’ survey with 10 questionnaires about preferences (Table 1) after the 2 week-treatment and medical review of clinical information of patients.

Results
A total of 80 patients (46 in ulcerative colitis and 34 in Crohn’s disease, and 54 of male) were enrolled. Previous use of CR mesalazine four 1 g-tablets a day more than 1 year was in 88.6% of patients. In preference of formulation by ease to swallow, 70.0% of patients answered 2 g-granule sachet was better but just 20.0% of patients answered 1 g-tablet was better. In preference of formulation by next prescription, that is about overall preference, 63.8% of patients answered granule was better but 30.0% for tablet. In the number of 1 g-tablet or 2 g-granule sachet able to be swallowed at once, 46.9% of patients could swallow one or less tablet (1 g or less) and 96.1% of patients could swallow one or two sachets (2 g or more) (Fig. 1). When the patients who chose ‘granule was much better or better in overall preference' are classified as granule preference group and the remaining as others group. Number of tablet able to be swallowed at once in the medication before the granule trial was significantly less in granule preference group compared to others group (1.6 tablet vs. 2.0 tablet) (Fig. 2). However, the other factors including age, sex, body weight, height, body mass index, type of disease, concomitant oral medications, previous duration of 1 g-tablet use, were not associated with the overall preference.

Conclusion
In patients already experienced CR mesalazine 1 g-tablet for a long time, two-thirds of the patients more preferred to be prescribed 2 g-granule sachet and the preference was associated with the ability to swallow 1 g-tablets at once. Not only CR mesalazine 1 g-tablet but also 2 g-granule sachet can be an excellent choice for improving adherence of mesalazine treatment in IBD, especially when it comes to patients who can't take two or more 1 g-tablets at once.
P540 Non-serious adverse events in patients with ulcerative colitis receiving etrasimod: An analysis of the phase 2 OASIS and phase 3 ELEVATE UC 52 and ELEVATE UC 12 clinical trials
Authors: Lees C , Torres J , Leung Y , Vermeire S , Fellmann M , Modesto I , McDonnell A , Lazin K , Keating M , Goetsch M , Wu J , Loftus Jr E V 
Published: January 2024

Abstract

Background
Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Adverse events (AEs) pertaining to tolerability, laboratory and serious AEs are described elsewhere1,2; we present a post hoc analysis of the incidence, onset and duration of the most commonly occurring non-serious AEs in the etrasimod UC clinical programme.

Methods
Data from the pooled Placebo-controlled UC cohort, derived from the phase 2 OASIS (NCT02447302) and phase 3 ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) double-blind clinical trials, were included. Cohorts comprised OASIS and ELEVATE UC 12 12-week induction periods alongside the ELEVATE UC 52 12-week induction and 40-week maintenance periods utilising a "treat-through" design. Patients (pts) with moderately to severely active UC were eligible for the etrasimod UC clinical programme. Pts were randomised to etrasimod 1 mg once daily (QD; OASIS only), etrasimod 2 mg QD or placebo. Proportions and incidence rates (IRs) of non-serious AEs (MedDRA v24.1 Preferred Terms of headache, pyrexia, nausea, fatigue and dizziness) were analysed in the Placebo-controlled UC cohort.

Results
Among 943 pts (any dose of etrasimod, N=629 [288.1 pt years (PY)]; placebo, N=314 [115.1 PY]), there were 77, 36, 30, 15 and 23 headache, pyrexia, nausea, fatigue and dizziness AEs, respectively. All were non-serious and did not lead to treatment discontinuation, apart from one case of pyrexia in which early termination visits were incomplete. Proportions and IRs (per 100 PY) for headache and dizziness AEs were higher with etrasimod (any dose) vs placebo (IRs: 13.45 vs 8.63 and 6.52 vs 1.69, respectively); IRs for other non-serious AEs were similar in etrasimod (any dose) and placebo groups (Table). Onset of AEs varied over time and most AEs were short in duration (Figure shows onset and duration for headache and dizziness AEs). Most AEs were deemed not related to study treatment by the site investigator. Pts with dizziness on Days 1–3 had similar changes in heart rate vs those with dizziness after Day 3. No consistent trend in heart rate was observed in pts receiving etrasimod with early dizziness.

Conclusion
Among pts in the etrasimod UC clinical programme, all headache, pyrexia, nausea, fatigue and dizziness events were non-serious. IRs were similar for most non-serious AEs across treatment groups, excluding headache and dizziness. Most non-serious AEs were short in duration and judged as not related to study treatment, suggesting they may not impact on the overall tolerability of etrasimod.
References
1. Sandborn WJ et al. Gastroenterology 2020; 158: 550–61.
2. Sandborn WJ et al. Lancet 2023; 401: 1159–71.
P555 Switching from intravenous vedolizumab to subcutaneous maintains clinical remission even in intensified patients with Inflammatory Bowel Disease. One year follow-up
Authors: Andres Pascual L , Arias García L , Saiz Chumillas R M , Chivato Martín-Falquina I , Sicilia Aladren B 
Published: January 2024

Abstract

Background
Vedolizumab is a humanized monoclonal antibody. It is indicated for moderate to severe flare of Inflammatory Bowel Disease (IBD). Subcutaneous (SC) vedolizumab, is a major advantage for patients for home administration. This study aimed to analyze the percentage of clinical and biochemical remission at 52 weeks in all IBD patients on treatment with intravenous (IV) vedolizumab after switching to the SC one.

Methods
Single-center, descriptive, observational, and retrospective study. The study included all the IBD patients (19 patients) who were at the moment of inclusion with IV vedolizumab treatment in a tertiary hospital, who underwent a switch from IV vedolizumab to SC vedolizumab. In addition, the relationship between treatment with intensified IV vedolizumab and subsequent drug levels versus patients without intensification for 52 weeks.

Results
Ten patients (22.6%) were diagnosed with Ulcerative Colitis (UC) and 9 patients (47.3%) with Crohn´s disease (CD). The baseline characteristics of the 19 patients are described in Table 1. Reasons for starting IV vedolizumab: there was loss of response to a first anti-TNF in 10 patients (52.6%) and loss of response to two previous anti-TNFs was observed in 3 patients (15.7%). In 4 patients (21%) IV vedolizumab was started as the first line of treatment due to the increased risk of infections and a previous history of neoplasia. Finally, in 2 patients with CD (10.5%) it was started as prevention of recurrence. Up to a total of 8 patients (42.1%) were on an intensified IV vedolizumab before switching to SC vedolizumab. All 19 patients (100%) were in clinical remission and 15 patients (78.9 %) remained in biochemical remission prior to switching to SC vedolizumab. At the end of the follow-up (52 weeks) all of them achieved clinical remission and 17 patients (89.4%) achieved biochemical remission (Figure 1). Therefore, biochemical remission was achieved in 10% more patients after the switch. It was noted that biochemical remission was achieved in 87% of patients on the intensified regimen with IV vedolizumab versus 100% of patients on the non-intensified regimen. No statistically significant differences were obtained between patients who had been on intensified IV vedolizumab and those who had not. At one year of follow-up, SC vedolizumab was suspended in one patient due to muscle pain, and IV vedolizumab was restarted again.

Conclusion
Following the standard dose switch of SC vedolizumab, clinical remission is maintained, achieving biochemical remission in 89.4 % of patients one year with SC vedolizumab with maintained vedolizumab levels, even in previously intensified IV vedolizumab patients.
P576 Fecal calprotectin could predict clinical and endoscopic response to ustekinumab therapy
Authors: Bertani L , Tricò D , Barberio B , Vernero M , Bretto E , Ceccarelli L , Pardi V , Calabrese F , Pasta A , Bertin L , Fabiana Z , Semprucci G , Bodini G , Ribaldone D G , Savarino E V , Costa F 
Published: January 2024

Abstract

Background
Ustekinumab (UST) is one of the most used biologic drugs for the treatment of Crohn’s Disease (CD) and Ulcerative Colitis (UC). However, not all patients achieve clinical remission and even less mucosal healing. There is currently scarce knowledge about the early markers of therapeutic response in this setting, with particular regard to mucosal healing. The aim of this multicenter study was to evaluate the role of fecal calprotectin (FC) as early predictor of mucosal healing.

Methods
We enrolled consecutive patients with CD or UC treated with UST for at least 48 weeks at four referral centers in the last 5 years. Therapeutic response was evaluated in terms of clinical remission (defined as a Partial Mayo Score &lt;2 for patients with UC and as Harvey Bradshaw Index &lt;5 for patients with CD, without concomitant corticosteroid therapy) and mucosal healing (defined as a Mayo Endoscopic Score &lt;2 for UC and as the disappearance of ulcers for CD). We collected clinical and demographic data, as well as fecal calprotectin (FC) and C-Reactive Protein (CRP) levels at baseline and at week 24.

Results
Among 196 patients enrolled (73 [37.2%] women), 167 were affected by CD, whereas 29 by UC. Globally, 128 (65.3%) patients achieved clinical remission and 83 (42.3%) endoscopic remission at 48 weeks of treatment. There were no group differences in age, sex, BMI, baseline clinical and endoscopic indexes, or baseline CRP levels between patients achieving or not either clinical or endoscopic remission. Baseline calprotectin levels were lower in patients who achieved endoscopic remission (median [interquartile range] 391 [103, 1050] versus 825 [317, 1800] µg/mL,p=0.002). At week 24, lower calprotectin levels were observed in both the groups who achieved clinical (160 [50, 426] versus 439 [146, 1000] µg/mL,p&lt;0.0001) and endoscopic remission (114 [43, 265] versus 392 [139, 912] µg/mL,p&lt;0.0001) compared with non-responders. The effects of week-24 calprotectin levels on clinical remission (β= -0.003,p&lt;0.0001) and endoscopic remission (β= -0.004,p&lt;0.0001) remained significant in multivariable models adjusted for age, sex, and BMI. A cut-point of 268 µg/mL was identified as the optimal threshold of week-24 calprotectin for predicting clinical remission (sensitivity 65%, specificity 67%, ROC AUC 0.689), while a cut-point of 309 µg/mL was identified to predict endoscopic remission (sensitivity 79%, specificity 59%, ROC AUC 0.712).

Conclusion
Our data suggest that FC assessment after 24 weeks of treatment with UST could represent a promising early marker of response, even in terms of mucosal healing, in both CD and UC.
P599 An Antioxidant diet in comparison to a Mediterranean diet for children and adults with Inflammatory Bowel Disease: clinical outcomes and nutritional data from OXIBDiet trial
Authors: Quattrini S , Galeazzi T , Greco A , Fioroni M C , Mattioli S , Monachesi C , Cianfruglia L , Romaldi B , Catassi G , Quatraccioni C , Di Sario A , Armeni T , Catassi C , Gatti S 
Published: January 2024

Abstract

Background
The multicentre OXIBDiet trial (NCT04513015) has already demonstrated a redox imbalance in IBD children compared to adults and controls. The second part of the study aimed to evaluate the impact of an Antioxidant Diet (AoD) in comparison to a Mediterranean Diet (MD) in IBD patients. Clinical outcomes and nutritional data are reported.

Methods
IBD children and adults with mild symptoms/remission were randomly assigned to AoD (polyphenols intake &gt;650 mg/die) or MD for 12 weeks. In the paediatric sample a Free Diet (FD) group was enrolled. At baseline and at 12 weeks inflammatory, oxidative stress (OS), clinical and anthropometric parameters were recorded. Dietary habits were registered by a validated Food Frequency Questionnaire and nutritional intakes were estimated with Winfood software.

Results
Twenty-five children (10 OD, 10 MD, 5 FD) and 17 adults (9 OD, 8 MD) completed the study. The total antioxidant capacity (Ferric reducing antioxidant power, FRAP) of the total IBD cohort significantly increased only in AoD (p=0.024) group and the Protein Oxidation (AOPP) showed a trend of decrease in AoD group (p=0.065). Stratifying for age, the same results of FRAP emerged only in the paediatric sample, following the AoD (Figure 1).
Weight z-score (p=0.04) and BMI z-score (p=0.054) increased significantly in children following the AoD. The AoD groups both in children and in adults showed respectively a significant improved in health status (p=0.016) and in Food Related QoL. Faecal calprotectin (FC) showed a trend toward reduction both in AoD and MD groups and an increase in the FD group. At week 0 dietetic habits and nutrients intakes were similar in children in the AoD and MD groups. Changes in nutrients intakes at week 12 for both groups are reported in Table 1. In AoD group of IBD children a significant positive correlation between FRAP and intake of polyphenols emerged (p=0.015).

Conclusion
Preliminary results showed a significant improvement in OS imbalance and anthropometric parameters in IBD subject following an AoD. Antioxidant micronutrients intakes increased in IBD children especially on AoD, with a positive effect on the total antioxidant capacity. Also, QoL and Faecal calprotectin showed a favourable trend in AoD group, both in children and in adults. Final results of the study will allow to clarify the role of oxidative stress and antioxidants in IBD pathogenesis and treatment.
P604 Exploring the role of chest X-ray in latent tuberculosis screening in Inflammatory Bowel Disease
Authors: Farrugia Y , Chatlani D , Camilleri C , Sciberras M , Ellul P 
Published: January 2024

Abstract

Background
Patients being treated with biologics or JAK inhibitors have an increased reactivation risk of latent tuberculosis infection (LTBI), and this is associated with a more severe infective course. Current ECCO guidance recommends the screening for LTBI by a combination of patient clinical data and epidemiological factors, chest X-ray (CXR), and tuberculin skin test or interferon-gamma release assay (IGRA) prior to starting immunosuppressive treatment. The evidence supporting CXR is categorized at evidence level 5, and information on its use in screening for LTBI originates from two decades ago. Apart from radiation exposure, a single posterior-anterior view has limited diagnostic capabilities.
This study aims to determine the relation between CXR findings and IGRA test results in patients undergoing LTBI screening before commencing immunosuppressive therapy for Inflammatory bowel disease (IBD) patients in a low-risk population.

Methods
This is a retrospective analysis whereby IBD patients (≥16 years) on biologics or JAK inhibitors were identified from our local database. The clinical data, epidemiological, CXR and IGRA result were then analysed from the electronic case records. The IGRA test used was the QuantiFERON-TB Gold.

Results
A total of 356 patients were included in the study, with 58.7% (n=209) being male. Among these patients, the majority had Crohn's disease (66.6%, n=236), 30.1% (n=109) had ulcerative colitis, and the remaining 2.8% were classified as having IBD-unclassified. Most patients (97.1%) had been exposed to anti-TNF alpha medications and 13.2% were exposed to multiple biologicals.
The mean age of IBD diagnosis was 30.3 years (SD+/-15.7). None of the patients had any clinical suggestion nor any evidence for exposure to TB.
None of the CXRs performed revealed any radiological signs of prior TB infection. 93.8% (n=334) of the IGRA results were negative and 4.2% (n=15) were categorized as indeterminate. Among those with indeterminate results, 66.7% (n=10) were undergoing corticosteroid treatment for active disease. The remaining 2.0% (n=7) had a positive IGRA test and were treated for LTBI.None of these patients had TB reactivation when then treated with biologicals.

Conclusion
This research highlights that performing routinely a CXR in individuals with a negative IGRA offers little to no benefit, and subjects patients to unnecessary radiation. It also demonstrates the importance of conducting the IGRA test early, before initiating any immunosuppressive treatment.
Furthermore, in patients with a negative IGRA, if chest imaging is required for screening purposes, opting for an ultra-low dose CT might be more prudent than a CXR, as it visualises the lungs better and the radiation exposure is not substantially different.
P606 A Retrospective Observational Study of Patterns of Biologic Drug Change in Inflammatory Bowel Disease
Authors: Mosli M H A 
Published: January 2024

Abstract

Background
The treatment of inflammatory bowel disease (IBD) has evolved over the past two decades. Due to the recent introduction of multiple new biologics, it is crucial to understand the temporal patterns of drug change. This study aimed to examine the patterns of biological drug change over time and identify predictors of change in a cohort of patients with IBD.

Methods
We performed a retrospective study of patients diagnosed with IBD who were initiated on biologics and followed up at King Abdulaziz University (KAU) hospital, Jeddah, Saudi Arabia between June 2017, and October 2022. The KAUH inflammatory bowel disease information system (IBDIS) database was used to identify eligible patients. The study's primary objective was to describe biologics drug change patterns. Secondary outcomes included identifying predictors of drug change and time to discontinue biologics. Uni- and multi-variable odds ratios (ORs) were used to determine the predictors of drug change.

Results
A total of 910 patients who were registered in the IBDIS database were screened; 475 patients fulfilled the study criteria. 67% had CD, and 53.3% were males. The mean age at diagnosis was 22.6 (11.0) years. The most selected first and second choice of biologic was adalimumab (58.2% and 39.1%, p&lt;0.001) and infliximab (37.6% and 48.9%, p=0.004) for both CD and UC, respectively. Ustekinumab was the primary third choice for CD (65.4%), while vedolizumab was the third choice for UC (83.3%). The proportions of patients who switched from first- and second-line adalimumab, infliximab, and vedolizumab were 52.3% and 20.9%, 37.6% and 39.9%, and 10.1% and 18.3%, respectively. On multiple regression analysis, a history of venous thromboembolism (VTE) (OR=3.60, 95% CI=1.20-11.71, p=0.025) and active smoking (OR=0.34, 95% CI=0.12-0.82, p=0.026) were associated with drug change for all patients. When stratified by disease subtype, drug change was associated with a diagnosis made between age 17 and 40 years (OR=0.46, 95% CI=0.23-0.90, p=0.024) and EIMs (OR=2.07, 95% CI=1.16-3.76, p=0.015) in CD while selecting vedolizumab as first biologic (OR=0.30, 95% CI=0.09-0.92, p=0.041), male gender (OR=2.40, 95% CI=1.04-5.73, p=0.043), and history of VTE (OR=7.32, 95% CI=0.23-49.97, p=0.031) were associated with drug change in UC.

Conclusion
Despite introducing several new biologics, anti-TNF therapies remain the preferred first and second choice of biologics for patients with IBD. The use of adalimumab is associated with the highest risk of switch. Multiple predictors of drug change over time exist for both diseases. The selection of vedolizumab as the first biologic for UC is associated with a lower risk of drug change.