bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0972 Higher vedolizumab clearance associates with poor therapeutic outcomes during maintenance therapy of vedolizumab in Crohn’s disease
Authors: Anjie MD S , D’Haens G R A M , Baert F , Bossuyt P , Hoentjen F , Clasquin E , Molnar T , Lowenberg M , Vermeire S , Panetta J C , Dervieux T 
Published: January 2025

Abstract

Background
Drug Clearance (CL) is a better pharmacokinetic (PK) metric compared to trough levels (TL) in associating with therapeutic outcome of infliximab, adalimumab and ustekinumab therapy in Crohn’s disease (CD). However, data regarding vedolizumab (VDZ) are limited. We compared the performances of VDZ CL and TL in associating with therapeutic outcomes in CD.

Methods
This retrospective analysis included a subset patients from the LOVE-CD trial at Amsterdam UMC. Blood samples were collected at trough during intravenous VDZ maintenance treatment and stored at -80ºC until analysis. VDZ TL were measured using homogenous mobility shift assay and CL was estimated using nonlinear mixed effect models. Therapeutic outcomes consisted of endoscopic remission (Simple Endoscopic Scoring for CD [SES-CD] &lt;3) measured at one-year after starting treatment, and clinical and biochemical remission status (CRP &lt;3 mg/L with CD activity index &lt;150) at each maintenance cycle. Statistical analyses included receiver operating characteristics (ROC) curves, area under the curve (AUC) and logistic regression.

Results
A total of 50 patients (24 females, mean age 37 years) were evaluated in this analysis. At one year 39 patients had endoscopic data; 17/39 (44%) were in endoscopic remission. In the 50 patients, 38% of cycles (120/312, median 6 per patients) showed clinical and biochemical remission. Median TL and CL were 16.0 µg/mL (IQR: 9.5-23.8 µg/mL) and 0.154 L/day (IQR: 0.125-0.190 L/day) respectively. Anti-drug antibodies to VDZ were negligible in this cohort (2.5%, 8/323 specimens). ROC analysis yielded higher AUC with CL (AUC= 0.824 [95%CI: 0.683-0.964]) than with TL (AUC=0.606 [95%CI: 0.421- 0.790]) (difference= 0.218 95%CI: 0.074- 0.362; p=0.003) in distinguishing endoscopic remission from endoscopic active disease. Similar results were observed with the clinical and biochemical remission outcome (AUC [conc]=0.530 [95%CI: 0.466-0.595] compared to AUC[CL]=0.646 [95%CI: 0.584- 0.709]) (difference: 0.116 95%CI: 0.063- 0.169; p&lt;0.001). Logistic regression revealed that TL were not significantly associated with either of the two outcomes (p&gt;0.28) (Figure). In contrast, higher CL (&gt;0.156 L/day) was associated with 9.0-fold (95%CI: 1.7,44.0) and 2.1-fold (95%CI: 1.3,3.4) lower likelihood of endoscopic and clinical & biochemical remission, respectively (p&lt;0.01) (Table).

Conclusion
These data support the hypothesis that VDZ CL is better than TL in associating with outcomes of VDZ treatment in CD. Given that there was little immune response to VDZ in this study, the association between higher CL and poor outcome most likely reflects higher inflammatory burden that consumes the drug from the central compartment.
P0982 Efficacy of upadacitinib in patients with Crohn’s disease and an ostomy: A matched retrospective real-world cohort analysis
Authors: Aldiabat M , Yarur A , Peyrin-Biroulet L , Loftus- Jr. E V , Colombel J F , Deepak P 
Published: January 2025

Abstract

Background
Upadacitinib (UPA) is an oral selective Janus kinase inhibitor approved for the management of moderate-to-severe Crohn’s disease (CD). One in ten CD patients may need a permanent ostomy (colostomy or ileostomy) during their disease course, and this may impact the efficacy of UPA, given its extended-release formulation. However, there is no data available in this population since patients with an ostomy are excluded from registrational CD trials. This study addresses this gap by comparing the real-world clinical effectiveness of UPA in CD patients with and without ostomy.

Methods
This retrospective cohort study analyzed data from the TriNetX US Collaborative Network of sixty-eight tertiary institutions, to examine adult (≥18 years) CD patients treated with UPA from May 19th, 2023 (FDA approval date) to October 31st, 2024. Patients were categorized based on presence or absence of an ostomy during the previous 5 years, after exclusion of patients with rheumatologic disease indications for UPA usage. A 1:1 propensity score matching (PSM) was performed to balance cohorts on demographics, baseline comorbidities, and CD severity indicators (CD phenotype, extraintestinal manifestations, concurrent corticosteroid and other biologics usage, hemoglobin, and body weight). Cox proportional hazards model estimated hazard ratios (HRs) in matched cohorts for clinical effectiveness as a composite outcome (corticosteroid use, hospitalizations, emergency room visits) and secondary individual outcomes, at one year post-treatment, with a significance threshold set at p &lt; 0.05.

Results
The study sample of CD patients on UPA included 170 with and 1,428 without a prior ostomy. There were 144 patients in each cohort after PSM. Baseline characteristics of the cohorts are shown in Figure 1. After PSM (Figure 2), there were no significant differences between patients with CD on UPA, with and without prior ostomy, for composite outcomes (HR 0.93, p = 0.64), corticosteroid use (HR 0.78, p = 0.18), hospitalizations (HR 1.13, p = 0.64), or emergency room visits (HR 0.99, p = 0.97). Additionally, no significant differences were observed in opioid use (HR 0.95, p = 0.76), switch to another advanced therapy (HR 1.62, p = 0.06), or elevated biomarkers, including CRP (&gt;10 mg/L, HR 1.00, p = 0.99) and fecal calprotectin (&gt;150 µg/g, HR 0.85, p = 0.63) at the 1-year follow-up.

Conclusion
In CD patients, UPA demonstrated similar effectiveness for clinical outcomes of corticosteroid use, hospitalizations, emergency room visits and other secondary outcomes, regardless of their ostomy status.
P0987 Muscle function deficits in Crohn’s Disease patients treated with Infliximab - tertiary single centre experience
Authors: Spirić J , Vuksanovic S , Toplicanin A , Nikolic A , Jovicic T , Jovicic I , Djuranovic S , Popovic D , Pavlovic Markovic A , Djelic M , Sokic-Milutinovic A 
Published: January 2025

Abstract

Background
Sarcopenia is an important consideration in the management of inflammatory bowel disease (IBD), in both prognosis and treatment. Since current data on sarcopenia in IBD are limited and based mostly on muscle quantity, it’s important to incorporate muscle function assessment into the evaluation of sarcopenia and to identify patient groups at increased risk.

Methods
A cross-sectional study included 84 Crohn’s Disease (CD) patients undergoing Infliximab therapy (64 males, mean age 34). Bioelectrical Impedance Analysis (InBody170) was done to estimate body composition parameters (BCP) which were then adjusted for height squared. Muscle strength was assessed by hand grip strength (HGS), measured using a dynamometer and muscle performance by gait speed test.

Results
Our results revealed that 6% of patients were underweight, 44% had normal body weight, 36.9% were overweight, and 13.2% obese. None of the patients exhibited low skeletal muscle mass index (SMI), however, half showed reduced muscle strength relative to age and sex adjusted norms in the general population. In relation to HGS, we found no significant differences in BCP, except for SMI (p=0.02) and body mass index (p=0.03), which were higher in patients with normal HGS. There were no differences between the groups in terms of physical activity levels, disease phenotype, prior surgeries, extraintestinal manifestations, clinical and endoscopic remission status. We observed significant differences in muscle quantity and quality based on disease localisation. Patients with ileocolonic CD had higher SMI (11.25±1.5 vs. 9.51±1.2 kg/m2, p=0.009) and HGS (41.1±6.6 vs. 31±6.7 kg, p=0.006) compared to those with colonic CD. Patients requiring biologic therapy due to immunosuppressive resistance had higher fat free mass index (19.4±2.4 vs. 18.2±3 kg/m2, p=0.05) and HGS (44.2 (24.9-45.3) vs. 39.3 kg (13.6-54.3), p=0.03), compared to patients on biologic therapy due to corticosteroid dependence or aggressive phenotype requiring top down approach. Patients diagnosed before 16 and after 40 years of age had lower gait speed (p=0.002), reflecting worse muscle performance.

Conclusion
Disease localisation, age at diagnosis and disease severity, as reflected by the indication for biologic therapy, may influence muscle composition and function. Our results emphasize the need for different and individualized management strategies based on disease localisation, especially in supporting muscle health among patients with isolated colonic CD and need for age-specific interventions, mainly in early and late onset CD, to support physical performance in these populations.
P0993 Prevention of Postoperative Recurrence of Crohn’s Disease: Comparison of Two Therapeutic Strategies
Authors: Amal J , Abdelwahab N , myriam A , zeineb B , nesrine H , bochra B , taieb J , rym E , Med Hedi D 
Published: January 2025

Abstract

Background
Postoperative recurrence of Crohn’s disease affects half of patients within 10 years, making prevention crucial. The ECCO recommends immediate postoperative prophylactic treatment for patients with at least one risk factor for recurrence. While this strategy is proven effective for those with multiple risk factors, data on its benefits compared to endoscopy-guided prophylaxis in patients with only one risk factor is lacking. The study aimed to compare immediate postoperative prophylactic treatment with endoscopy-guided prophylaxis in patients with a single risk factor

Methods
This retrospective bicentric study included patients who underwent ileocolic resection for Crohn’s disease between January 2011 and December 2021, each with one risk factor for postoperative recurrence. Patients were divided into two groups G1 received immediate postoperative prophylactic treatment, while G2 received prophylactic treatment guided by colonoscopy within the first year after surgery. The primary outcome was the frequency of endoscopic recurrence within one year :Rutgeerts score ≥ i2. Secondary outcomes included severe endoscopic recurrence (i4) within 12 months and clinical recurrence at 6 and 24 months. Statistical analysis was conducted using SPSS26

Results
This study included 41 patients divided into two groups. Group 1 (24 patients) had an average age of 34 years, with 58.33% being active smokers.Postoperative treatments were as follows: infliximab (4 patients), infliximab-azathioprine combination (3 patients), adalimumab (4 patients), ustekinumab (1 patient), and azathioprine monotherapy (12 patients). A Rutgeerts score of i2 or higher was found in 13 patients after a median of 9 months post-surgery, with an average follow-up of 3 years
Group 2 (17 patients) had an average age of 38 years, with 64.7% being active smokers. Postoperative colonoscopy was performed after a median delay of 8 months. A Rutgeerts score of i2 or higher was found in 10 patients. The treatments initiated after colonoscopy were as follows: infliximab (3 patients), infliximab-azathioprine combination (2 patients), adalimumab (7 patients), azathioprine monotherapy (4 patients), and ustekinumab (1 patient). The average follow-up after surgery was 3 years
No significant differences were observed between the groups in terms of endoscopic or severe endoscopic recurrence, or clinical recurrence at 6 and 24 months post-surgery

Conclusion
In our study, early initiation of prophylactic postoperative treatment for patients with a single risk factor did not reduce clinical or endoscopic recurrence rates. This suggests that avoiding such early treatment could help prevent unnecessary exposure to immunosuppressants and biologics, thereby reducing risks of side effects and high costs
P1018 Diyushengbai tablets alleviate azathioprine-induced leukopenia in patients with Crohn’s Disease
Authors: Zeng Z , Yuan J , Zhang H 
Published: January 2025

Abstract

Background
Azathiopurine (AZA) is the classic immunosuppressant for crohn’s disease (CD) and plays a critical role in induction and maintenance of remission, facilitation of mucosal healing, and prevention of postoperative recurrence. The incidence of azathiopurine-induced leukopenia (AIL) in Asians is high, posing a serious challenge for clinical medication. Diyushengbai tablets are synthetic traditional Chinese medicine, widely used to prevent and treat leukopenia caused by chemotherapy. It remains unclear about its role in treating AIL. Ziyuglycoside II is the key ingredient of Diyushengbai tablet. The mechanism of Ziyuglycoside II in preventing AIL is yet unclear. Therefore, the objectives of this study are to explore the effects of Diyushengbai tablets in the treatment of AIL and the possible mechanism of Ziyuglycoside II in the prevention of AIL.

Methods
CD patients with AIL were prospectively enrolled. The leukocyte counts of CD patients before, four weeks, and eight weeks after taking Diyushengbai tablets were collected. AIL mouse models were established by intragastric administration of AZA (10mg/kg) treated with or without Ziyuglycoside II (5mg/kg and 10mg/kg). The leukocyte counts of mice were measured at weeks 0, 1, 2, and 3. The bone marrow cells of mice were extracted for flow cytometry.

Results
21 CD patients with AIL were enrolled in this study. The leukocyte counts before, four weeks, and eight weeks after treatment were 2.96±0.42×109/L, 3.48±0.73×109/L, and 4.26±1.85×109/L, respectively. Diyushengbai tablets increased the leukocyte counts at week four (P=0.004) and week eight (P&lt;0.001), respectively. They maintained the leukocyte counts no less than 3.0×109/L in 76.19% (16/21) and 85.71% (18/21) of patients after four-week and eight-week treatment, respectively. They also prevented more than 95% (20/21) of patients from withholding AZA in those who developed AIL during the eight-week following-up. The decrease of leukocyte counts was significantly lower in the Ziyuglycoside II-treatment group compared with the AIL group. Ziyuglycoside II treatment increased the number of hematopoietic stem and progenitor cells (HSPCs) including long-term hematopoietic stem cells (LT-HSCs), short-term hematopoietic stem cells (ST-HSCs), and multipotent progenitor cells (MPPs).

Conclusion
Diyushengbai tablets can be used to treat AIL. They increase the leukocyte counts and prevent most CD patients with AIL from withholding AZA. Ziyuglycoside II increases the leukocyte counts and prevents AIL by stimulates the proliferation and differentiation of HSPCs. These findings highlight a promising role of Diyushengbai tablets in treating AIL.
P1019 Role of Oncostatin M (Osm)-Osmr signaling in colonic inflammation and host defense during citrobacter rodentium infection
Authors: Luo Y , Cineus R , Bösel D , Cancino C , Blazquez L V , Konopka A , Hegazy A N 
Published: January 2025

Abstract

Background
Elevated Oncostatin M (OSM) and its receptor (OSMR) are linked to the pathology of inflammatory bowel disease (IBD), particularly in severe, treatment-refractory cases. While anti-OSM therapies hold potential for IBD management, their impact on susceptibility to acute enteric infections remains unclear. This study aims to clarify the role of Osm-Osmr signaling in the context of Citrobacter rodentium infection, a murine model mimicking acute colonic inflammation.

Methods
Temporal studies were conducted on C57BL/6J mice infected with C. rodentium, assessing gene expression, bacterial load, and immune dynamics at days 3, 7, 14, and 21 post-infection. Histological analysis and flow cytometry were performed to evaluate inflammation and immune infiltration. Additionally, Osm knockout (KO) and Osmr conditional KO mice were utilized to investigate the role of OSM signaling in pathogen control and immune responses.

Results
Colonic expression of Osm and Osmr peaked at day 14, concurrent with increased levels of Il-22, IFN-g, and antimicrobial peptides (Reg3b, Reg3g), indicating robust immune activation and epithelial repair. ELISA confirmed elevated OSM protein levels. Histology at day 14 revealed severe colonic inflammation, with high Osm/Osmr expression correlating with inflammation scores (p &lt; 0.0001). Flow cytometry showed increased CD45⁺ immune cells, including neutrophils, monocytes, and memory T cells. Notably, OSM signaling was dispensable for bacterial clearance, as Osm knockout mice displayed comparable bacterial loads to wild-type controls despite similar inflammatory responses, suggesting that OSM’s role may be more focused on modulating inflammation and tissue repair rather than direct pathogen control.

Conclusion
Osm-Osmr signaling plays a key role in modulating inflammation and epithelial repair during C. rodentium infection. The coordinated upregulation of OSM and OSMR enhances immune responses and supports epithelial integrity, highlighting potential therapeutic implications for IBD. Further research is needed to assess the impact of anti-OSM therapies on balancing inflammation control and host defense against infections.
P1046 Risk Factors for Complications After Crohn’s Disease Surgery : A tertiary monocentric study
Authors: Aouroud H , Aouroud M , Lairani F E , Nacir O , Ait Errami A , Oubaha S , Samlani Z , Krati K 
Published: January 2025

Abstract

Background
Crohn’s disease needs a multidisciplinary approach, and surgery will ultimately be necessary for most patients. Complications usually occur after surgery.

Objective
This study aims to present complication rates in surgically treated Crohn’s disease patients at a single institution and to determine possible risk factors and also to determinate the impact of anti-tumor necrosis factor (TNF) agents on the postoperative course.

Methods
This was a single-center retrospective study that included 121 CD patients who underwent elective ileo-coecale resection (ICR) in a tertiary center between January 2016 and September 2024. Risk factors for overall postoperative complications (POC) and intra-abdominal septic complications (IASC) were assessed with univariate and multivariate analyses.

Results
Over 121 patients, 77 (63%) were male and 44 (39%) were female, the mean age of our population was 27+/- 7,5 yo, The most common early complications were wound infection (22%) and intra-abdominal abscess formation (14%) and The incisional hernia was the most common late complication (n = 4, 3.6%). In multivariate analysis, anti-TNF agents (n=57), as either monotherapy or combination treatment, were not associated with an increased risk for overall POC (P=0.71) or IASC (P=0.83). Patients with colonic involvement (P = 0.001), penetrating disease character (P = 0.037), concomitant fistula and intra-abdominal abscess existence (P = 0.043), disease duration &gt;10 years (P=O,OO4), or previous intestinal resections had significantly higher rates of both overall POC and IASC.

Conclusion
Preoperative administration of anti-TNF agents or other immunosuppressive regimens was not a risk factor for total POC or IASC. A Colonic involvement, penetrating disease, fistula, concomitant abscess and fistula correlated with both overall POC and IASC.
P1107 Biosimilar but not quite the same?: Post-induction levels of infliximab differ between brands
Authors: Patel P , Love M , Rimmer P , Cooney R , Hazel K 
Published: January 2025

Abstract

Background
Infliximab is used for the induction and maintenance of clinical remission in Crohn’s disease and ulcerative colitis. Our trust underwent a switch from the infliximab preparation Inflectra to the biosimilar Remsima in 2022. We wished to analyse if levels of treatment persistence and response were similar between brands as anecdotally we observed a potential higher rate of primary treatment failure, loss of response and requirement for dose escalation of Remsima when compared to Inflectra post-induction.

Methods
Patients were identified from our IBD database. Post-induction levels of infliximab were assessed. Infliximab levels pre- and post-switch from Inflectra to Remsima were assessed. Rates of dose escalation and switch to alternative agents and reasons for switch were also examined. Statistical analysis was completed using Mann-Whitney U test and Fisher’s exact test.

Results
In total, 82 patients were included in our analysis; 42 with Crohn’s disease and 40 with ulcerative colitis. 35 received induction with Inflectra and subsequently switched to Remsima. 47 patients received Remsima induction. Post-induction levels with Inflectra showed a mean of 8.08 mcg/ml when compared to Remsima levels of 5.01 mcg/ml (p = 0.02642). Pre-switch levels of Inflectra were almost equivocal at 8.44 mcg/ml when compared to maintenance levels of 8.57 mcg/ml (p = 0.177) for Remsima. 13 patients (27.7%) who received Remsima induction required dose-escalation compared to 20% of those induced with Inflectra (p = 0.4508). 40% of patients on Inflectra switched to another class of biologic were switched due to loss of response/failure to respond or inadequate drug levels with high antibodies compared to 47% of those switched from Remsima (p = 0.621) for the same reasons.

Conclusion
Post-induction trough levels of infliximab differ between brands. This should be taken into consideration when considering higher dosing at induction or for those patients treated with infliximab for acute severe colitis and earlier accelerated dosing should be considered in those patients treated with Remsima who have a slow clinical response to treatment. Trough levels once established on the drug appear to be similar and rates of switching out of class due to failure to respond/loss of response and antibody formation comparable.