bluuebunny/crossref_metadata_2025_split huggingface dataset:
P863 Prospective outcome following ustekinumab treatment in a real-world cohort of inflammatory bowel disease patients
Authors: Ramos Lopez L , Ramos-Díaz R , Benítez-Zafra F , Morant-Domínguez A , Vera-Santana B , Mourani-Padrón I , Alonso-Abreu I , Carrillo-Palau M , Reygosa C , Medina-Chico J S , Gutierrez-Nicolás F , Nazco-Casariego J , Hernández-Guerra M 
Published: January 2024

Abstract

Background
Therapeutic drug monitoring (TDM) serves as a valuable tool for improving efficacy and reducing rates of drug toxicity .However, the utility of TDM with non-anti-TNF agents (such as Ustekinumab-UST) is less well defined, although it may be useful in optimizing UST posology and improving efficacy. In this study, we aimed to evaluate clinical outcomes and UST plasmatic concentration in real-world IBD patients.

Methods
A prospective study was conducted including IBD patients who initiated UST therapy between August 2020 and June 2023. Clinical outcomes were prospectively collected (clinical remission as Harvey-Bradshaw Index (HBI) &lt;4 or partial Mayo score (pMS)≤1; biochemical remission as fecal calprotectin (FC)&lt;150 g/kg); physician global assessment (PGA) (active/ not active) and patient-reported outcome (IBDQ-9)) and UST plasmatic concentration was assessed by ELISA every 8 weeks for 12 months. The need for drug escalation, surgery, hospitalization, or discontinuation of treatment at the end of the follow-up (September 2023) was recorded.

Results
A total of 91 patients were included (population described in Table 1). After a median follow-up of 12 (9.6-10.7) months, clinical remission was observed in 90.4% of CD and 66.6 % of UC patients, 52.7% presented biochemical remission and 61.5% of IBD patients were inactive by PGA. 81% of patients showed a good quality of life as measured by IBDQ-9 &gt;60 points. 9.9% needed IBD hospitalization and only 1 (1.09%) patient required IBD surgery. UST-dose escalation was indicated for 33% of patients, mainly in UC patients (UC 46.1% vs CD 28.1%; p=0.42). Treatment discontinuation was required in 13.2% (12/91) of patients after a median follow-up of 15 (14.8-19) months, due to loss of response in 66.6% of these patients (Figure 1A).
The mean UST concentration at induction (8 weeks) was significantly higher than at maintenance (16 weeks) (9.2 (7.7-10.7) µg/ml vs 4.8 (3.9-5.7); p&gt;0.0001); no differences in UST concentration were found during the maintenance treatment (Figure 1B). UST concentration was not related to age, sex, body mass index, type of IBD, or previous exposure to biological agents. In multivariate analysis, UST concentration &gt;7 µg/ml in maintenance (16 weeks) showed an independent predictive value for IBD hospitalization (OR 7.6, 95% CI 2.5-23.1) and UST-dose escalation (OR 4.1, 95% CI 1.4-11.9) in the next 12 months.

Conclusion
Ustekinumab (UST) is an effective treatment, bringing about clinical remission and an enhanced quality of life for individuals with inflammatory bowel disease (IBD). In our prospective cohort, UST concentration at maintenance serves as a predictive indicator of IBD outcome.
P865 Screening for low-processed breads - compositional analysis of food additives used in commercially available breads
Authors: Shakhman S , Pfeffer-Gik T , Elial-Fatal S , Broitman Y , Yanai H , Gophna U , Dotan I , Godny L 
Published: January 2024

Abstract

Background
Ultra-processed food (UPF) intake has been associated with the development of inflammatory bowel diseases (IBD), particularly Crohn’s disease (CD). Of UPF subgroups, commercially available breads showed greater risk, possibly due to the increasing presence of food additives (FA) like emulsifiers. As bread is a staple food worldwide, often consumed daily, we aimed to screen the ingredients and FA used in bread industry and to assess the availability of low processed breads.

Methods
We consecutively screened breads available at supermarket and health food store chains popular and widely distributed in Israel. Breads, pita breads and buns (excluding products without food labels), were analyzed by dietitians and categorized into one of three categories according to their processing level and FA types. Low processed category included ingredients used in traditional, home-made breads; medium processed category included FA like malt and added fibers; high processed category included FA like emulsifiers and preservatives, previously associated with impact on microbiota composition or implications on IBD.

Results
A total of 233 breads were screened, 160 are available at the supermarket, 56 at the health food store, and 17 in both. We categorized 195 (84%) as highly processed, 9 (4%) as medium processed and 29 (12%) as low processed. We identified 36 different types of FA and ingredients used. Most breads contained emulsifiers- 178 (76%) and –preservatives-189 (81%). The most used emulsifier was sodium stearoyl-2-lactylate (SSL, E-481), present in 86 breads (37%), followed by mono- and diglycerides of fatty acids (E-471), DATEM (E-472e) and carboxymethyl cellulose (CMC, E-466), found in 22%, 16% and 2% of breads, respectively. Interestingly, the emulsifier E-481, previously shown to induce microbial alterations, was found in 86 breads (52%) sold in the supermarket compared to none of the breads available in the health food store. Out of the 5 common preservatives, most of the breads contained calcium propionate (E-282) found in 112 (48%) and potassium sorbate (E-202) found in 42 (18%). Additives like enzymes were present in 159 (68%), gluten was added to 148 (64%) and 88 (38%) breads had added fibers. A greater portion of the breads contained yeast (85%) compared to sourdough (47%), with 30 (13%) containing only sourdough.

Conclusion
Most of the commercially available breads in Israel are highly processed. The use of emulsifiers, preservatives, added gluten and fibers is very common, yet low processed breads are available. These may be more recommended to patients with IBD. Further understanding of the role of FA in IBD etiology may potentially guide dietary recommendations for specific food choices.
P866 Management of fistulizing Crohn's Disease in a moroccan population: about 125 cases
Authors: Aouroud H , Aouroud M , Lairani F E , Nacir O , Ait errami A , Oubaha S , Samlani Z , Krati K 
Published: January 2024

Abstract

Background
Crohn's disease is an inflammatory enterocolitis, which may be complicated by enteroenteric, enterovesical, rectovaginal, enterocutaneous and anoperineal fistulas. This is a retrospective study of fistulizing Crohn's disease cases followed in our gastroenterology department.

Methods
We report a retrospective and descriptive study, covering all cases of fistulizing Crohn's disease, collected in the hepato-gastroenterology department at our university hospital center during a 9-year study period, from 2015 to 2023. All patients with digestive and/or anal crohn's fistula were included. Comparison of categorical variables was performed with Fisher's exact test using SPSS 10.0 software. The significance level was p &lt; 0.05.

Results
125 patients had a fistulizing form of Crohn's disease. The location of fistulas was represented by anoperineal fistulas (32.6%), followed by enteroenteral (22.9%) and enterocutaneous (23%) fistulas, then enterovesical (9%) and rectovaginal (3.8%) fistulas. Surgical treatment was immediately indicated in all cases of enterocutaneous and enterovesical fistulas, and 66.7% of rectovaginal fistulas. Proctological drainage was performed in 57.1% of cases of anoperineal fistulas. 33 cases of anoperineal fistulas and one case of recto-vaginal fistulas were treated with infliximab. Clinical remission was also significantly associated with medical treatment with biologics versus immunosuppressants (P=0.0018). Surgical treatment remains indicated in the majority of cases of fistulizing Crohn's disease.

Conclusion
Fistulizing Crohn's disease poses a problem for medical and surgical management. Surgical treatment remains indicated in the majority of Crohn's fistula cases. This study also showed that endoscopic recurrence and clinical remission were significantly associated with the type of postoperative medical treatment.
P867 Abdominally targeted yoga-based physical exercises as a therapeutic intervention for Inflammatory Bowel Diseases
Authors: Izhar R , Werner L , Fibelman M , Shapiro I , Siderskyi A , Ostrinski Y , Hirsch A , Ron Y , Fliss Isakov N , Maharshak N 
Published: January 2024

Abstract

Background
Physical activity (PA) has positive effects on general well-being and stress. The effect of abdominally targeted PA on IBD disease measures and patient’s quality of life (QoL) is currently unknown.
We aimed to examine the effect of routine, abdominally targeted, physical exercise sets, designed exclusively for IBD patients, on patients’ QoL and clinical response.

Methods
This randomized (1:1), controlled, double-blinded study assessed the effect of a set of 10-minute videos of specific abdominally targeted physical exercises inspired by Yoga, postulated to increase blood flow to the abdomen, on patients' disease activity and QoL, compared to a control general exercise videos. All patients signed an informed consent form. Patients performed either abdominally targeted (intervention) or control exercises, sequenced and performed by a trained and experienced yoga instructor, through an online application, at least 5 times/week.
Disease activity (HBI/ SCCAI), inflammatory indices (CRP, fecal calprotectin), and QoL measures (PROMIS questionnaire), were compared before and after 30-days of the intervention. For collective analysis of patients, a combined clinical score scale was used (Table 1). Change in calprotectin was calculated as the initial minus the end value.

Results
Twenty-six mild-moderate patients with IBD (age 39.3±10 years) were randomized to perform either intervention (8 CD, 7 UC), or control (7 CD, 4 UC) sets of exercise. Upon completion, most IBD patients training with either the interventional or control videos, exhibited significant improvements in their clinical scores. Among the patients in the interventional arm, the clinical score decreased from 1.1±0.4 to 0.4±0.6 (p&lt;0.001), and in the control group from 1.4±0.5 to 0.9±0.7 (p&lt;0.01). Interestingly, calprotectin significantly decreased only in the interventional group, in comparison to the control (Delta calprotectin: 40.8±122 vs. -431±652μg/g, respectively, p≤0.01). No improvements were observed in CRP. QoL measures improved in the intervention group in pain (13.6±14%, p&lt;0.005), anxiety (14.3±24%, p&lt;0.05), fatigue (18.8±19%, p&lt;0.05) and in social activities (7.1±9%, p&lt;0.05). In contrast, in the controls, only anxiety score improved (8.3±9%, p&lt;0.05). No differences were observed in scores of sleep disturbances, depression, and physical function in either group.

Conclusion
Routine PA can significantly improve IBD clinical scores and symptoms. Abdominally targeted exercises are associated with an additional improvement in clinical scores, fecal calprotectin and in self-perceived level of interference in pain and routine daily functions. These results suggest a positive effect of physical exercise in IBD and prompt further study.
P869 Deep ulcers in acute Ulcerative Colitis at index endoscopy predict corticosteroid resistance
Authors: Goncalves J , Macedo Silva V , Macedo C , Arieira C , Cúrdia Gonçalves T , Dias Castro F , Magalhães J , João Moreira M , Cotter J 
Published: January 2024

Abstract

Background
Ulcerative Colitis (UC) is a chronic inflammatory disease affecting the colon. Its acute form can be life-threatening, necessitating hospital admission and intravenous (IV) corticosteroid treatment. This study aimed to predict IV corticosteroid response in acute UC patients based on endoscopic findings at admission.

Methods
Individuals admitted to the hospital for acute UC for intravenous corticosteroid treatment were selected. Those with gastrointestinal infections and those without endoscopy at admission were excluded.

Results
A retrospective analysis was conducted on a cohort of 62 patients, of which 25.8% did not respond to IV steroids. No significant associations were found between demographic, clinical, and laboratory parameters and corticosteroid response at admission. Rectosigmoidoscopy was performed for all patients upon hospitalization, and the Mayo Endoscopic Score (MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) were obtained. The results revealed significant differences in median UCEIS scores between non-responders and responders (7, IQR 3 vs. 5, IQR 1, p=0.011). Notably, a UCEIS score of ≥5 demonstrated a sensitivity of 100% in identifying patients who did not respond to corticosteroids, although with a lower specificity of 22.7%. Furthermore, the MES exhibited a statistically significant association with treatment response (p=0.002), with a MES≤2 having a negative predictive value of 92.9% for IV steroid resistance. Importantly, the presence and type (small vs. large) of ulcers at the initial endoscopy were found to be the most effective predictive factor for corticosteroid response (AUC=0.745; 95%CI=0.594-0.896; p=0.005), as 57.1% of patients with deep ulcers were non-responders.

Conclusion
The importance of evaluating ulcer severity during endoscopic assessment in patients with acute ulcerative colitis is underscored by our findings. Notably, the presence of deep mucosal ulcerations should prompt consideration for intensifying therapy.
P873 Ustekinumab Real World Evidence Study (UndieS): Assessing the suitability of patients treated in routine clinical care for participation in the pivotal phase 3 clinical trial
Authors: Young D , Booker C , Batchelor J , Bodger K , Cummings F 
Published: January 2024

Abstract

Background
Phase 3 randomised controlled trials (RCTs) are recognised as the gold standard for measuring the efficacy of new medicines and are essential for licensing new products. To maximise internal validity, RCTs recruit a highly selected, carefully defined group of participants, whereas patients treated in routine practice are much more heterogeneous. We set out to describe the real-world use of ustekinumab and assess the proportion of treated patients who would have been eligible for the relevant registration studies.

Methods
UndieS is a UK-based, multicentre, prospective, observational study investigating the effectiveness of ustekinumab in 593 Crohn’s disease patients. Objective evidence of active Crohn’s disease (biochemical or endoscopic) and/or failure or intolerance to another therapy were the only entry criteria. Within the limits of the study, we compared participants’ characteristics with the eligibility requirements of the UNITI clinical trial programme. The pragmatic modified Harvey-Bradshaw Index (mHBI), shown to correlate to CDAI score, was used in UndieS. No endoscopic follow up information was collected.

Results
82% of patients treated in this real-world study would not have been eligible for participation in the UNITI programme. Eight RCT eligibility criteria would each be expected to exclude at least 10% of the real-world patient population (figure 1). A low disease activity score was the eligibility criterion most frequently expected to render UndieS participants ineligible for the UNITI programme with 61% of predicted CDAI scores (i.e. estimated from mHBI) falling below the threshold for RCT eligibility, despite 80% of those treated having objective evidence of inflammation and 55% failed/ were intolerant to an alternative therapy. Only 13% of participants were using corticosteroids at baseline. 59% of UndieS participants had previously failed or been intolerant to at least one anti-TNFα medication. For those who would have been ineligible for the RCT based on laboratory tests, an elevated ALT was the commonest abnormality among UndieS participants. The requirements for multiple venepunctures and pregnancy avoidance were the most relevant impediments for UndieS patients, with 28% of females of childbearing potential not willing to agree to the specified conditions.

Conclusion
Within the limitations of this study, we have demonstrated a significant disparity between participants in phase 3 RCTs and patients treated in routine clinical care. This questions the applicability of efficacy studies to real world clinical practice. Data from high quality, observational studies should complement findings from RCTs to support decision makers. Future work will investigate whether outcomes differ according to RCT eligibility.
P877 A comparison of vedolizumab and ustekinumab treatment in patients with Ulcerative Colitis after failure of treatment with tumor necrosis factor inhibitor
Authors: Helm Wiken T E , Høivik M L , Buer L , Warren D J , Bolstad N , Anisdahl K , Lundekvam J , Hagen M , Medhus A W 
Published: January 2024

Abstract

Background
Data comparing vedolizumab (VDZ) and ustekinumab (UST) in patients with ulcerative colitis (UC) previously treated with tumor necrosis factor inhibitor (TNFi) and followed with regular serum-drug measurements are scarce. In the national pharmaceutical tender system of Norway, VDZ was listed as the first drug of choice after failed TNFi treatment from 2016 to 2019 and UST from 2020 to 2022. We aimed to compare drug persistence, effectiveness, drug dosing and disease activity in patients treated with VDZ or UST after failed TNFi therapy.

Methods
We included patients who had failed at least one TNFi and started either VDZ treatment (years 2016-2019) or UST (years 2020-2022). Patients were followed for one year after initiating the treatment or until discontinuation. Prospectively recorded data were obtained from the electronic patient journal (EPJ) and the local IBD-registry. Clinical remission was defined as 6-point Mayo Score ≤1, and biochemical remission was defined as CRP&lt;5 mg/L and FC&lt;250 µg/g. Patients were followed with regular serum-drug measurements and dose adjustments were made at the discretion of the treating physician based on serum-drug measurements and clinical activity at follow-up visits. Wilcoxon signed rank and Mann Whitney U test were used to assess differences in paired and unpaired data, respectively.

Results
A total of 116 patients were included, 59 treated with VDZ and 57 with UST. At 52 weeks, there was no difference in estimated drug persistence with 85% [73-92] for VDZ and 92% [80-96] for UST. Clinical remission increased significantly in both groups (Table 1), and no difference was found between UST and VDZ for clinical remission at week 0 and 52 (OR=2.1 [0.9-4.5] and OR=0.9 [0.3-2.3]). Contrary to the VDZ group, there was a significant decrease in CRP from week 0 to 52 in the UST group, while FC decreased significantly in both groups (Table 1). The proportion of patients in biochemical remission increased in the UST group while there was no significant change in the VDZ group. Significantly more patients treated with UST received an intensified treatment regime at 52 weeks (interval less than eight weeks) compared to VDZ treated patients (87% (95% CI [74-94]) vs 59% (95% CI [45-72])).

Conclusion
This study demonstrates that one-year drug persistence and clinical remission were high and comparable in both UST and VDZ treated UC patients with previous TNFi failure. Treatment with UST, but not VDZ, was associated with a significant increase in the proportion of patients in biochemical remission from induction to 52 weeks. However, a significantly larger proportion of patients treated with UST received intensified dosing at 52 weeks compared with VDZ treated patients.
P878 Assessment of Ulcerative Colitis Relapse Risk Using RDI (Red Dichromatic Imaging)
Authors: Hashimoto Y , Itoi Y , Tomaru S , Sato K , Tanaka H , Shiko K , Yoji T , Uraoka T 
Published: January 2024

Abstract

Background
In the management of patients with UC, mucosal healing has been proven to be a therapeutic goal and a factor influencing prognosis. It has been reported that MES 1 has a higher rate of recurrence than MES 0. However, it has been reported that MES 0 also has a relapse rate of approximately 10%. Red dichromatic imaging (RDI) is a new imaging technology that has been closely correlated with the activity index of UC. (Naganuma et al. Endosc Int Open 2017). It also correlates with histological findings and holds promise as a modality that could further stratify MES 0 (Hashimoto et al. Surgical Endosc 2023). However, it is unclear whether RDI findings is associated with UC relapse. The aim of this study was to investigate the predictive ability of RDI for UC relapse.

Methods
This was a single-center retrospective study. A total of 93 clinically remitted UC patients who underwent colonoscopy at our department from May 2019 to October 2021 were enrolled, and at least one RDI and WLI image was taken at each of six sites from the cecum to the rectum. Patient information and still images of RDI and WLI were blinded, and two physicians independently evaluated both images taken using the RDI score of Naganuma et al. Clinical remission was defined as partial Mayo Score (pMayo) 0-1, and relapse was defined as pMayo ≥ 2 and additional treatment.

Results
The median after observation was 1022 days (5-1427 days), and the overall cumulative relapse rate was 24 % (21 patients), The mean of RDI score was 2.02, with 37 patients in RDI score 1, 28 patients in RDI score 2, 17 patients in RDI score 3, and 11 patients in RDI score 4. The relapse rate for RDI score 1 was 0%, 18% (5 patients) for RDI score 2, 47% (8 patients) for RDI score 3, and 73% (8 patients) for RDI score 4.73 % (8 patients).None of the patients with RDI score 1 had a relapse, In contrast, 11% (6 of 54) of MES 0 patients relapsed, and 33% (8 of 24) of MES 1 patients relapsed. 31 patients had RDI score 1 and 17 patients had score 2 in MES 0, which could be stratified within MES 0 by using the RDI.

Conclusion
This study suggested that the RDI score can further stratify MES 0, which is defined as mucosal healing, and may be a more accurate predictor of relapse.