bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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 < 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 (>10 mg/L, HR 1.00, p = 0.99) and fecal calprotectin (>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

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

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

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<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

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 < 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

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 >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

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.
P1116 Imaging of CCR9 in the small bowel of patients with Crohn’s disease: effects of the CCR9-depleting monoclonal antibody AZD7798
Authors: Hedin C R , Creignou M , MacKay J , Jucaite A , Cselényi Z , Johnström P , Dahl K , Schou M , Cortés González M A , Högnäsbacka A , Stenkrona P , Blomqvist L K , Cananau C , Palmér E , Bouma G , Eck S , Lund J , Lundahl A , Kiraga J , Popińska A , Eberhardson M , Belvisi M G , Marks D J B
Published: January 2025

Background

Management of patients with small bowel Crohn’s disease (SBCD) remains challenging due to limited efficacy from current therapeutic options. AZD7798 is a first-in-class monoclonal antibody for CD that depletes CCR9+ lymphocytes, with potential for targeted treatment of SBCD given the critical role that CCR9 plays in lymphocyte homing to the small bowel. Monitoring CCR9+ cell depletion and repletion in the blood is straightforward, but difficult in the small bowel due to accessibility for biopsy. Here we use positron emission tomography (PET) with a novel CCR9-specific PET tracer, [11C]vercirnon, to assess the ability of AZD7798 to deplete CCR9+ cells in the intestines of healthy volunteers and patients with SBCD.

Methods

We performed an open-label phase 1b study to evaluate the effects of single and repeat intravenous doses of AZD7798 on intestinal [11C]vercirnon uptake in healthy volunteers and patients with SBCD (NCT06053424). Additional endpoints were safety and pharmacodynamics in blood (CCR9 cell depletion). PET imaging using [11C]vercirnon was performed prior to AZD7798 dosing and at 2 follow-up timepoints, approximately 2 and 6 weeks post dosing.

Results

A total of 6 healthy (aged 25-64 years, 4 female) and 6 SBCD participants (aged 24-59 years, 4 female) completed the study. There were no major adverse tolerability or safety findings following single or repeat doses of AZD7798. Mild cytokine release syndrome (CTCAE Grade 1) was observed after first doses, but not after second doses in the repeat dose cohort. There were no serious adverse events or treatment discontinuations due to adverse events.

In 4 out of 6 SBCD participants, PET imaging showed a quantitative reduction in [11C]vercirnon uptake of up to 21.6% (median 11.5%) in the intestines at 6 weeks following single (n = 3 out of 4) and repeat (n = 1 out of 2) IV doses of AZD7798 (Figure 1). Rapid, profound and sustained CCR9+ cell depletion was observed in blood in all healthy and SBCD participants (Figure 2).

Conclusion

The use of a CCR9-specific PET tracer has enabled repeatable, non-invasive quantification of CCR9 expression in the gut. Preliminary evidence of intestinal CCR9+ cell depletion in patients with SBCD following single and repeat doses of AZD7798 was provided. The study demonstrates the value of molecular imaging for understanding treatment effect in the target tissue in vivo. An ongoing PET imaging study will assess the effects of AZD7798 on CCR9+ cell depletion/repletion in the gut following multiple doses, alongside Phase 2 studies evaluating the clinical efficacy of AZD7798 in moderate-to-severe Crohn’s disease.
P1119 Distinct clinical features in IBD patients undergoing orthotopic liver transplantation: Associations with re-transplantation and overall survival
Authors: Wiestler M , Taubert R , Wedemeyer H , Wranke A , Lenzen H
Published: January 2025

Background

Orthotopic liver transplantation (OLT) in patients with inflammatory bowel disease (IBD) represents a special patient population with high heterogeneity. The management of IBD in liver transplant recipients is challenging due to the need to balance immunosuppressive therapy, IBD flares and graft survival. Therefore, detailed analysis of clinical parameters is essential to better understand outcomes and optimize management strategies in this unique cohort.

Methods

This monocentric, retrospective analysis included IBD patients with concomitant OLT at our tertiary referral center. We reviewed the local database for incident cases from January 2013 to December 2023. Identified patients have been evaluated based on demographic data, detailed IBD and OLT history, complications (including re-OLT), and overall survival.

Results

This study included 126 IBD patients with OLT, with a mean age of 37.3 years at transplantation and a mean age of 28.2 years at IBD diagnosis. The majority of patients were male (68.3%), and ulcerative colitis (UC) was the most common diagnosis (86.5%), followed by Crohn’s disease (CD) (11.9%). Among UC patients, 79.8% had extensive colitis (E3), while in CD patients, the distribution was 40% L1, 26.7% L2, and 33.3% L3. The most common indication for OLT in this cohort was PSC (74.6%), followed by PSC/AIH variants (13.5%). Before OLT, 42.1% of patients were treated with corticosteroids, while 56.8% continued steroid treatment after OLT. Aminosalicylates were prescribed to 69.2% of patients pre-OLT, but only 49.6% continued this treatment post-OLT. 90.4% of patients did not require advanced therapies after OLT, though biologics like vedolizumab and ustekinumab were used in a small subset. 27.2% of patients required re-OLT, with UC being the most prevalent IBD entity for re-transplantation (82.4%). Colectomy after OLT was performed in 12.7% of patients, and it was associated with a higher likelihood of re-OLT (p = 0.04; OR: 3.1; 95% CI: 1.06-9.1), while post-OLT 5-ASA therapy was associated with a reduced likelihood of re-OLT (p = 0.03; OR: 0.4; 95% CI: 0.17-0.9). Overall mortality post-OLT was 26.2%. A COX-Regression analysis further revealed significant associations with overall mortality and e. g. age at IBD diagnosis (p < 0.01; HR: 1.07; 95% CI: 1.04-1.11), male sex (p = 0.045; HR: 2.95; 95% CI: 1.02-8.52), steroid use post-OLT (p=0.04: HR: 2.6, CI: 1.06-6.43) and PSC (p=0.04: HR: 0.3, CI: 0.11-0.95).

Conclusion

To the best of our knowledge, this is the largest monocentric IBD OLT cohort. We identified 5-ASA and steroid therapy as modifiable risk factors for re-OLT and mortality in IBD patients after OLT. Further validation of these findings in a larger multicentric setting is recommended.
P1125 Robotic ileo-cecal resection in Crohn´s disease patients is feasible regardless of disease phenotype – first experience of a referral IBD centre
Authors: Podmanicky D , Ferko A , Kadleckova B , Zelinkova Z
Published: January 2025

Background

Over the past years, minimally invasive surgical approach for inflammatory bowel diseases (IBD) has been prioritized with increasing but still limited evidence supporting the use of robotic surgery. The data available are mainly dealing with rectal and colonic interventions whilst the experience with small bowel resections is scarce and the role of robotic surgery in patients with complicated ileocolonic disease is debated.Thus, the aim of this study was to analyse the outcomes of minimally invasive procedures, laparoscopic vs. robotic ileo-cecal resections in a prospective cohort of Crohn´s Disease (CD) patients.

Methods

All CD patients undergoing laparoscopic or robotic ileo-caecal resection in one referral IBD centre between August 2023 and November 2024 were included. Differences between the two groups in basic demographics, disease phenotype and duration, treatment at the time of surgery, nutritional status, number of previous surgeries and reason for surgery were analysed. Duration of surgery, time to first bowel movement, any short-term complications and hospital stay were compared between the two respective surgical approaches. The patients were assigned to laparoscopic or robotic group based on logistic availability.

Results

In total, 37 patients with CD were included (mean age 38 years, range 20-69; 17-47% were women; mean disease duration 7.3 years, range 0-37). Twenty-six patients were operated laparoscopically, 11 underwent robotic surgery.

The two groups did not differ in any of the above-mentioned preprocedural characteristics, including the proportion of stenosing and penetrating phenotypes. There were no differences in nutritional status (mean BMI 22.6±0.84 vs. 22.4±1.1 in laparoscopic vs. robotic group, respectively, p=0.913) with weight loss prior surgery being equally present in both groups (11.5% vs. 9.1% in laparoscopic vs. robotic group, respectively, p>0.9999).

Mean duration of the procedure was significantly longer in the robotic group (216 minutes, range 120-316 in the robotic group vs. 147 minutes, range 75-300 in laparoscopic group, respectively; p=0.002). The two groups did not differ in the mean hospital stay (6.3, range 4-14 vs. 5.6, range 4-8; laparoscopic vs. robotic surgery, respectively, p=0.331); nor in time to first bowel movement (1.9, range 1-4 vs. 2.4, range 1-4; laparoscopic vs. robotic group, respectively, p=0.14). There were two surgical site infections in the laparoscopic group and one ileus treated conservatively in the robotic group.

Conclusion

Robotic ileo-caecal resection is feasible in Crohn’s disease patients regardless of disease phenotype and the type of Crohn’s disease complication for which the surgery is performed.
P1129 Comparison of discontinuation/switching between adalimumab biosimilar and originator in Inflammatory Bowel Disease patients: Preliminary data from CAN-AIM
Authors: Lukusa L , Birck M G , Moura C S , Neville A , Zezos P , Narula N , Targownik L E , Ma C , Purdy E , Afif W , Singh H , Oketola B , Bernatsky S
Published: January 2025

Background

Biosimilar adalimumab (ADA-B) has been approved in Canada for inflammatory bowel disease (IBD) for over eight years, but real-world descriptions of therapy persistence (discontinuation/switching) comparing ADA-B to its bio-originator (ADA-O) are still scarce. We compared discontinuation of ADA-B and ADA-O in IBD.

Methods

CAN-AIM is a team funded to do high-priority research projects for Health Canada and other stakeholders. Canadian IBD Research Consortium members contributed to CAN-AIM’s prospective pan-Canadian clinical registry of biosimilar/bio-originator users. We enrolled adults with a clinical diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC), starting a bio-originator or corresponding biosimilar from Feb 2009 to Mar 2024. We assessed time to discontinuation through Kaplan-Meier curves with a log-rank test (right-censoring at loss to follow-up or end of study) and reasons for discontinuation. Using multivariable Cox regression, we assessed time to drug discontinuation, comparing ADA-B and ADA-O. Covariates included age, sex, underlying condition (CD/UC), disease duration, race and ethnicity, calendar year, smoking, education, disease activity (moderate or severe: Crohn’s Disease Activity Index ≥220, Harvey-Bradshaw Index ≥8 or Partial Mayo Score ≥5), obesity (body mass index >30), comorbidity, and prior use of other biologics, as well as previous/current corticosteroids and non-biologic immunosuppressants.

Results

We followed 103 IBD individuals for a median of 5.0 years (interquartile range of 3.6 to 9.2). IBD duration, age, race and ethnicity, and smoking were comparable among the two groups (Table 1). We censored four individuals who changed from ADA-O to ADA-B due to provincial drug insurance formulary requirements. There were 37 (35.9 %) other discontinuations, or 133.9 events per 1000 person-years. The main reasons for discontinuation were secondary loss of response (n=20, 54.1% of 37) and adverse events (n=7, 18.9%). Other reasons included insurance changes (n=2), patient choice (n=1), and unknown or missing reasons (n=7). Median time to discontinuation was 4.0 years (95% confidence interval [CI] 1.4-5.8) for ADA-O and 6.7 (95% CI 3.6-9.2) for ADA-B. Risk of discontinuation was lower in ADA-B versus ADA-O, with a wide CI (adjusted hazard ratio [aHR] 0.46, 95% CI 0.22–0.97 – Table 2). Older age, female sex, UC, higher education, more recent calendar year, and corticosteroids were significantly associated with discontinuation.

Conclusion

In this real-world IBD analysis, ADA-B was not associated with a greater risk of discontinuation.
P1134 The effectiveness of medical therapies for dermatological extraintestinal manifestations in patients with IBD: an umbrella review
Authors: Noor N , Prabhu A , Lim A , Krishnakumar A , Yuan Y , Jairath V
Published: January 2025

Background

Patients with IBD can develop various extraintestinal manifestations (EIMs), including those affecting the skin. These dermatological EIMs may or may not mimic the disease course of the underlying IBD, can have a significant impact on quality of life for patients and a major influence on treatment decisions. We conducted an overview of systematic reviews (umbrella review) to assess the effectiveness and safety of medical treatments for managing dermatological EIMs in patients with IBD.

Methods

In this umbrella review, we searched major databases (MEDLINE, Embase and Cochrane CDSR,) for relevant systematic reviews published until May 2024, that aimed to review the medical interventions of the dermatological EIMs. Screening, data extraction, and quality appraisal (using AMSTAR 2) were performed by at least two reviewers and any discrepancies resolved by a third independent reviewer.

Results

Of 1436 screened papers, 11 systematic reviews met our inclusion criteria. These 11 systematic reviews evaluated the effect of medical therapies across five dermatological EIMs in patients with IBD, with some systematic reviews considering more than one EIM: psoriasis (n=2), erythema nodosum (n=3), pyoderma gangrenosum (n=7), Sweet’s syndrome (n=1) and cutaneous vulval Crohn’s disease (n=1) (Table 1). For psoriasis, low response (14%) was reported to methotrexate but with high levels of remission with ustekinumab (82%), and no additional benefit of methotrexate combination with ustekinumab. For erythema nodosum, high levels of response were reported for anti-TNF therapies (80-100%), vedolizumab (50-62%) and ustekinumab (70%). For pyoderma gangrenosum, a more variable response was reported for anti-TNF therapies (21-92%), vedolizumab (33%) and ustekinumab (75%). For Sweet’s syndrome corticosteroids were reported to be effective in most, with limited data on more advanced therapies. For cutaneous vulval Crohn’s disease metronidazole was associated with 23% complete healing with limited data on more advanced therapies. There were no published systematic reviews on effectiveness of IL-23 specific p40 antagonists or oral small molecules. Effectiveness data was mostly descriptive and generally high levels of response were reported to the above treatments. Overall the certainty in the results of the reviews was low.

Conclusion

Although dermatological manifestations are common for patients with IBD, the evidence-base for medical interventions to treat these dermatological EIMs is limited and heterogeneous. These results outline the need for dedicated research studies to better determine the effectiveness and safety of medical therapies to treat dermatological manifestations specifically in patients with IBD.
P1137 Prognostic value of intestinal ultrasound (IUS) in patients with Acute Severe Ulcerative colitis (ASUC) – A single center experience
Authors: Zacharopoulou E , Bellou G , Palatianou M , Pagoni A , Internos I , Leontidis N , Neokleous A , Tribonias G , Tzouvala M
Published: January 2025

Background

There is scarce evidence in the role of intestinal ultrasound (IUS) as a prognostic tool in patients with Acute Severe Ulcerative colitis (ASUC).

Methods

The study included hospitalized patients with ASUC that were assessed by IUS within 48 hours after intravenous corticosteroids (CS) initiation. Demographic characteristics of the patients, as well as response to corticosteroids, necessity of rescue therapy and/or urgent colectomy were recorded. Bowel wall thickness (BWT), modified Limberg score (mLimberg), loss of bowel stratification in left (LC), transverse (TC), and right (RC) colon, as well as the presence of mesenteric hypertrophy, enlarged lymph nodes, free fluid in peritoneal cavity and pneumatosis intestinalis were compared between CS responders and non-responders.

Results

Six patients participated in total (5 males) with a mean age of 73 years (±11) and a mean disease duration of 82 months (± 103). Three patients responded to CS. Among the non-responders, two underwent urgent colectomy and one received rescue therapy with Infliximab. The mean disease duration was lower in the non-responders. BWT was higher in LC in both patient groups but, RC BWT was statistically higher in non-responders group (6,3±0,3 vs 2,4±0,3, p=0,0001). Higher values of mLimberg score were observed in LC, however in non-responders, mLimberg was higher in every bowel segment. Total loss of bowel wall stratification in all colonic segments and free peritoneal fluid were recorded only in the non-responders group. Pneumatosis intestinalis and mesenteric hypertrophy were recorded mainly in the non-responders, whereas enlarged lymph nodes were found in both groups.

Conclusion

IUS is a useful non-invasive diagnostic tool for monitoring patients with ASUC and it may probably have a prognostic value regarding the patients’ response to CS. The thicker bowel wall in RC, the complete loss of bowel wall stratification, the presence of free peritoneal fluid and pneumatosis intestinalis are associated with CS failure. Larger studies including larger populations are essential in order to establish the role of IUS in patients with ASUC.

References

1.Ilvemark JFKF, Wilkens R, Thielsen P, et al. Early Intestinal Ultrasound Predicts Intravenous Corticosteroid Response in Hospitalised Patients With Severe Ulcerative Colitis. J Crohns Colitis. 2022;16(11):1725-1734. doi:10.1093/ecco-jcc/jjac083

2.Allocca M, Dell’Avalle C, Craviotto V, et al. Predictive value of Milan ultrasound criteria in ulcerative colitis: A prospective observational cohort study. United European Gastroenterol J. 2022;10(2):190-197. doi:10.1002/ueg2.12206
P1139 A real-world, observational study comparing the side effects of budesonide MMX with prednisolone and the resolution of symptoms in patients with mild to moderate ulcerative colitis
Authors: Walsh C , Ulaganathan H , Van Der Merwe K , Parihar V
Published: January 2025

Background

Budesonide MMX is indicated for the induction of remission in mild to moderate Ulcerative Colitis (UC) patients when 5-ASA treatment is not sufficient. There is limited real-world evidence of the relative side effects following budesonide MMX treatment using prednisolone as a benchmark and the time to resolution of symptoms following initiation of budesonide MMX exists.

Methods

Between July 2022 and August 2024, 27 patients with mild to moderate UC, based on clinical assessment, received the treatment. Patients initially completed a nurse-led questionnaire regarding their experiences with prior prednisolone treatment. Following subsequent flare therapy with budesonide MMX, patients completed a nurse-led follow-up questionnaire.

Results

A comparison of the patient-reported side effects is shown in Figure 1. Following prednisolone treatment, side effects were reported in 26% (n=7) of patients compared to 7% (n=2) following treatment with budesonide MMX. Mood disturbance was reported in 11% of patients following prednisolone and 4% following budesonide MMX. Sleep disturbance was reported in 7% of patients following both treatments. Moon face, weight gain, insomnia and acne were reported following prednisolone but not budesonide treatment.

The time to resolution of symptoms following treatment with budesonide MMX is shown in Figure 2.

Following 1 week of budesonide MMX flare therapy, rectal bleeding was resolved in 37% of patients rising to 67% by week 4. Stool frequency was resolved in 33% of patients in week 1 and 78% by week 4.

Conclusion

The overall incidence of patient-reported side effects was significantly higher (P<0.001) following prednisolone treatment compared with budesonide MMX. This suggests that budesonide MMX may be a better tolerated treatment option for patients with mild to moderate UC. Some prednisolone-related side effects were not reported following treatment with budesonide MMX. Of those that were, only 1 patient reported that they affected daily life, indicating that budesonide MMX may have a lower impact on patients’ daily activities.Either rectal bleeding or stool frequency was resolved in over three quarters of patients by week 4 of flare therapy with budesonide MMX.
P1162 Novel use of risankizumab in children with refractory Crohn’s disease : Case series
Authors: Alsarhan A , Tzivinikos C
Published: January 2025

Background

Pediatric Inflammatory bowel disease (IBD) is generally more aggressive and difficult to treat compared to adulthood IBD. The only biological agent approved for use in this population is Anti-TNF medications (Adalimumab and Infliximab). Other medications such as anti IL-23 and/or IL-12 antibodies are not officially approved, yet the adult literature showed efficacy even in refractory cases priorly exposed to biologics. Given the delay of new medications approval in children, we present the novel use and real world experience of risankizumab which is a p19 anti IL-23 antibody in children with refractory Crohn’s disease.

Methods

We present 5 cases of Crohn’s disease who have failed at least 1 biological agent, including Adalimumab, Infliximab, ustekinumab, Azathioprine and methotrexate. All of them developed pharmacodynamic loss of response to Anti-TNF and one patient developed neutralizing antibodies. MR enterography was showing active ileal disease prior to commencing risankizumab. One Patient had developed Pyoderma gangrenosum, and another patient underwent pan-endoscopy which showed inflamed mucosa. C-reactive protein and ESR did not correlate with disease activity or response to the medication. risankizumab was administered as per the protocol . After 1 year follow up, all patients were in clinical remission with normal calprotectin. Bedside intestinal Ultrasounds was done and showed normal bowel wall thickness. Pyoderma gangrenosum improved significantly as well. Only one patient had MR enterography after 1 year which was unremarkable. No side effects were observed within the follow up period.

Results

We demonstrate that risankizumab has been used for 5 patients who already lost response to one or two biological medications. This medication successfully induced clinical and radiological remission after 1 year. risankizumab could be used after Adalimumab, Infliximab or even ustekinumab. Despite lack of approval, cautious use of new biological agents might be the only choice to avoid surgical resection in refractory Crohn’s disease. No side effects were documented over short term follow up. Additionally, Pyoderma gangrenosum responded after treatment.

Conclusion

Risankizumab can be an effective choice in pediatric Crohn’s disease patients who have lost response to other biological treatment and who had surgical resection as well. Patients maintained remission over 1 year follow up, and did not exhibit any side effect.

References

Zare B, Gros B, Lal N, et alEffectiveness of risankizumab induction and maintenance therapy for refractory Crohn’s disease: a real-world experience from a preapproval access programme and early access to medicines schemeFrontline Gastroenterology 2024;15:499-506.
P1182 Risk of surgery in patients with newly diagnosed Crohn's disease is declining along the 21st century
Authors: Kontola K , Oksanen P , Huhtala H , Helavirta I , Ilus T
Published: January 2025

Background

The repertoire of biological medication for Crohn’s disease (CD) has expanded in the past two decades. The impacts of these new therapies on surgery rates are still under investigation. Our aim was to analyse the surgery rates in newly diagnosed CD patients in the biological era in all age groups.

Methods

Newly diagnosed CD patients were collected from the registry of Social Insurance Institution of Finland and data on surgeries from the Finnish Institute for Health and Welfare. Patients were stratified according to the diagnosis year and the availability of medication to three groups: 2000-2006 (infliximab era), 2007-2013 (anti-TNF era with infliximab and adalimumab available) and 2014-2020 (multiple biologicals available). The subgroups were defined as paediatric (aged <20), adults (aged 20-59), and the elderly (aged ≥60).

Results

We identified 11,329 newly diagnosed CD patients, of whom 1,959 were operated. The cumulative risk of surgery was 8.2%, 13.8%, and 18.7% in 1, 5, and 10 years postdiagnosis, respectively. Overall, the 1- and 5-year risks were declining (incidence rate ratio (IRR) 0.97, CI 0.96-0.98 and IRR 0.98, CI 0.97-0.99, respectively), yet the 10-year risk showed no change (IRR 0.99, CI 0.98-1.01). The paediatric group (IRR 1.24, CI 1.10-1.39) and the elderly (IRR 1.20, CI 1.07-1.34) had higher risk of surgery compared to the adults. Also, men had higher risk of operation (IRR 1.20, CI 1.10-1.32). Adults had lower operation risk in later eras compared to infliximab era (IRR 0.55, CI 0.49-0.619). However, the paediatric group demonstrated reduction only in the last era (IRR 0.25, CI 0.18-0.34), and the elderly had stable risk (IRR 1.04, CI 0.82-1.31). The most common operation type in the primary operation was ileocecal resection (39%), followed by procedures in colon (32%) and small bowel (23%). Only in the elderly subgroup the most frequent procedure was colon resection (37%), followed by small bowel (32%) and ileocecal procedure (26%).

Conclusion

The risk of surgery among newly diagnosed CD patients is declining along the 21st century. Risk is also declining in the paediatric population, whereas the risk of the elderly has stayed constant.
P1183 Multivariable analysis of baseline variables associated with efficacy outcomes in the ELEVATE UC clinical programme
Authors: Feagan B G , Kayal M , Schreiber S , Abreu M T , Banerjee R , Fellmann M , Abbatemarco A M , Woolcott J C , Wu J , Goetsch M , Keating M , Rubin D T
Published: January 2025

Background

Baseline (BL) variables that accurately predict responses to advanced therapies have potential to improve ulcerative colitis (UC) management. Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active UC. BL data from patients in the ELEVATE UC clinical programme were used to identify variables associated with etrasimod response.

Methods

In this post hoc analysis of ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369),1 efficacy endpoints of clinical remission and endoscopic improvement, and change from BL in modified Mayo score (MMS) and endoscopic subscore (ES), were analysed using logistic or linear regression models, respectively, at Weeks 12 (pooled data) and 52 (ELEVATE UC 52 only). BL variables pre-selected by univariate regression analyses (≥1 comparison p<0.1) associated with efficacy outcomes were further assessed using multivariable logistic/linear regression using backward selection (stay criterion p<0.05).

Results

At Week 12, BL corticosteroid use (no vs yes, odds ratio; 95% confidence interval: 0.61; 0.41, 0.90), a BL ES of 3 vs 2 (0.44; 0.30, 0.64) and higher high-sensitivity C-reactive protein (hsCRP) (≥0.5 to <3 vs <0.5 mg/L: 0.43; 0.24, 0.77) were independently associated with lower odds of achieving clinical remission. Biologic/Janus kinase inhibitor (bio/JAKi) naïve vs experienced was associated with higher odds of achieving clinical remission at Week 52 (2.02: 1.13, 3.61). Similar variables were associated with endoscopic improvement at Week 12. At Week 52, a BL MMS 4–6 vs 7–9 (2.23; 1.38, 3.60) was linked with increased odds of achieving endoscopic improvement (Figure). At Week 12, higher hsCRP (≥0.5 to <3 vs 0.5 mg/L, least squares mean difference: 0.62), a BL ES of 3 vs 2 (0.48) and bio/JAKi exposure (naïve vs experienced: -0.42) were associated with change from BL in MMS, and higher disease activity (hsCRP ≥0.5 to <3 vs <0.5 mg/L: 0.27; ES 3 vs 2: -0.43) with change from BL in ES; most associations were not observed at Week 52 (Table).

Conclusion

In this analysis, BL variables related to higher disease activity were associated with lower odds of achieving efficacy endpoints at Week 12. These were not associated with all efficacy endpoints at Week 52, suggesting some patients may require more time to achieve clinical outcomes.

References

1.Sandborn WJ et al. Lancet 2023; 401: 1159–1171.

Pfizer’s generative artificial intelligence tool MAIA was used to assist production of the abstract first draft. Authors reviewed/edited and take responsibility for the content.