bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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 &lt; 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

Abstract

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&gt;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

Abstract

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 &gt;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

Abstract

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

Abstract

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

Abstract

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&lt;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

Abstract

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.