bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0611 Effectiveness comparisons between tofacitinib, filgotinib and upadacitinib in ulcerative colitis: results from the JAKARTA real-world evidence multicenter study
Authors: Buisson A , Treton X , Nachury M , Uzzan M , Bouguen G , Banana Hamadidi A , Amiot A , Serrero M , Fumery M , Caillo L , Hupé M , Pereira B , Altwegg R 
Published: January 2025

Abstract

Background
As no direct comparisons exist, we compared the effectiveness of tofacitinib (TOFA), filgotinib (FILGO) and upadacitinib (UPA) in patients with Ulcerative Colitis (UC).

Methods
In this retrospective multicenter study, we included all consecutive patients with UC ≥18 years-old, partial Mayo score &gt; 2 who had started TOFA, FILGO or UPA after receiving ≥ 1 biologic.
Following regimen were applied : TOFA (10mg b.i.d --&gt; at W8: 5mg or 10 mg b.i.d according to physician’s judgement), FILGO (200mg q.d) and for UPA (45mg q.d --&gt; at W8: 45mg, 30 mg or 15 mg q.d according to physician’s judgement).
The primary endpoint was symptomatic remission (partial Mayo score ≤ 2) without corticosteroids (CFREM) at W16. Secondary endpoints were clinical-endoscopic remission (CFREM + endoscopic Mayo score ≤ 1), histological-endoscopic mucosal improvement (HEMI) (= clinical-endoscopic and histological remission (Nancy index ≤ 1)), drug retention and secondary loss of response.
Comparisons were performed using propensity scores adjustment (IPTW).

Results
Overall 290 UC patients were included: TOFA=150, FILGO=79, UPA=61. The 3 groups were comparable except for higher proportion of patients with partial Mayo score &gt; 6 or prior exposure &gt; 3 biologics in UPA group (p &lt; 0.001).
Recommended maintenance dose (TOFA 5mg b.i.d/UPA 30 mg/FILGO 200 mg) from W8 after response to induction was applied in 41.3% (62/150), 65.8 % (52/79), and 59.0% (36/61), in TOFA, FILGO and UPA groups, respectively, and failed (need for dose re-escalation/drug discontinuation/no clinical remission at last follow-up) in 58.1% (36/62), 42.3% (22/52), 30.5% (11/36), in TOFA, FILGO and UPA groups, respectively, (p &lt;0.001).
After IPTW, CFREM at W16 was higher in UPA (60.1%) compared to TOFA (38.9%) or FILGO groups (36.8%) (p &lt; 0.001 for both). No predictor of efficacy/ failure was identified with these 3 JAK inhibitors. We failed to show any significant difference regarding clinical-endoscopic remission (UPA:16.5%, TOFA:16.5%, FILGO:12.8%) or HEMI (UPA:11.9%, TOFA: 4.4, FILGO: 12.7%).
Among patients achieving CFREM at W16 (regardless of the dose), secondary loss of response (clinical relapse) was similar across the groups (TOFA:12.8%, FILGO: 19.2% and UPA: 10.3%; p = ns after IPTW).
After adjustment, drug retention was longer for UPA compared to TOFA and FILGO groups (HR = 0.42 [0.21-0.85], p = 0.016) and shorter in FILGO than in TOFA group (HR = 1.60 [1.07-2.38], p = 0.021). No difference was demonstrated in terms of time to hospitalization or surgery between the 3 groups.

Conclusion
In this real-world evidence study, UPA was the most effective JAK inhibitor in UC at short and long-term but the large use of off-label maintenance doses in current practice needs further safety investigations.
P0616 ViT-based deep learning and unsupervised clustering analysis in Crohn’s Disease based on body composition to identify distinct phenogroups and predict the effectiveness of anti-TNF therapy
Authors: Wang Y , Ding Z , Zhang M , Li Y 
Published: January 2025

Abstract

Background
Anti-TNF therapy is considered as a crucial treatment in Crohn’s disease (CD). However, it has a primary nonresponse rate in up to 30% of patients and secondary loss of response rate of about 5% per patient-year with unknown reason. Herein, we aimed to establish an artificial intelligence algorithm to identify patients with beneficial response and predict the effectiveness of anti-TNF theray based on body composition.

Methods
Between July 2020 and August 2023, 105 CD patients who underwent anti-TNF therapy from Shanghai Ninth people’s Hospital were enrolled in this study. An unsupervised clustering analysis (K-means clustering) was utilized to classify subjects into distinct groups based on body composition parameters before anti-TNF therapy. We analyzed the relationship between different phenogroups and the response to anti-TNF therapy. Besides, radiomics features were extracted from subcutaneous fat (SF), visceral fat (VF), and skeletal muscle (SM) at the level of L3/L4 based on CTE. A deep learning model based on Vision Transformer (ViT) was established to predict the response of anti-TNF therapy.

Results
Our analysis identified three phenogroups: Cluster 1 (PhAhigh/BCMhigh/BMChigh/SMIhigh/BMIhigh/proteinhigh/IWhigh/EWhigh), Cluster 2 (PhAlow/BCMlow/BMClow/SMIlow/VFAhigh/BFPhigh/proteinlow/IWlow/EWlow) and Cluster 3 (VFAlow/BMIlow/BFPlow). Patients in Cluster 1 showed best response of anti-TNF thrapy (p = 0.023). Among patients in Cluster 3, those with high nutritional risks showed significantly earlier loss of response than those with low nutritional risks (p = 0.041). The prediction model achieved satisfactory accuracy in predicting the effectiveness of anti-TNF therapy (SF: AUC = 0.700; VF: AUC = 0.745; SM: AUC = 0.785) in the validation cohort.

Conclusion
Patients with good nutritional status have a better response to anti-TNF therapy in CD. Earlier loss of response occurred in patients with high nutritional risks, which may be improved by nutritional support. Subcutaneous fat, visceral fat, and skeletal muscle at the level of L3/L4 showed a satisfactory performance in predicting the response to anti-TNF therapy.
P0618 A Network Meta-analysis to Compare the Efficacy of Advanced Treatments for Biological-Experienced Patients with Ulcerative Colitis
Authors: Kulkarni A , Giri S , Joshi H 
Published: January 2025

Abstract

Background
Multiple therapeutic options are now available for the treatment of steroid-refractory ulcerative colitis. As the understanding of the disease pathophysiology evolves, new molecular targets are being unfathomed. Biologicals and oral small molecular agents are the established drugs for steroid-refractory UC. However, about 40% of patients fail to respond to biologicals at the onset (primary non-response) or on follow-up (secondary loss of response). The myriad therapeutic options do not have a head-to-head comparison in biological-exposed UC. We performed a network meta-analysis to compare the therapeutic efficacy of various molecules currently approved across the globe for biological-exposed UC.

Methods
The electronic databases of MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus were searched from inception to September 2024 for randomized studies comparing the outcome of advanced therapies in patients with prior exposure to biologicals. Induction and maintenance of remission were the primary outcomes assessed using frequentist network meta-analyses.

Results
For induction of remission, Vedolizumab (RR 2.22, 1.02–4.84), Filgotinib (RR 2.47, 1.07–5.70), Risankizumab (RR 2.77, 1.24–6.18), Etrolizumab (RR 2.93, 1.29–6.65), Upadacitinib (RR 4.82, 2.74–8.48) Etrasimod (RR 5.24, 1.20–22.87), Tulisokibart (RR 9.00, 1.20–67.45), Ustekinumab (RR 9.76, 2.36–40.27), and Tofacitinib (RR 10.23, 2.04–51.38) were significantly better than placebo. Tofacitinib (RR 6.56, 1.05–40.85 and RR 6.11, 1.09–34.05), Ustekinumab (RR 6.25, 1.19–32.86 and RR 5.83, 1.26–27.04), and Upadacitinib (RR 3.09, 1.10–8.66 and RR 2.88, 1.27–6.51) were significantly better than both Adalimumab and Mirikizumab, respectively for induction of remission. Based on an analysis of the SUCRA plot, Tofacitinib was the best therapy, followed by Ustekinumab, Tulisokibart, Upadacitinib, and Etrasimod.
For maintenance of remission, data from re-randomized studies showed that Upadacitinib (7.04, 2.51-19.79), Vedolizumab (5.12, 2.04-12.80), Filgotinib (3.48, 1.06-11.39), and Mirikizumab (3.06, 1.15-8.14) were significantly better than placebo. Upadacitinib (4.95, 1.30-18.88) and Vedolizumab (3.60, 1.03-12.57) were significantly better than Risankizumab for maintenance of remission. Based on an analysis of the SUCRA plot, Upadacitinib was the best therapy, followed by Vedolizumab, Etrasimod, Filgotinib, and Mirikizumab.

Conclusion
In this network meta-analysis, JAK inhibitors (JAKIs) were superior to other therapies for induction as well as maintenance of remission. While Tofacitinib had the best chances of inducing remission in biological-exposed UC, maintenance of remission was higher with Upadacitinib.
P0624 Adherence to a Care Pathway for Inflammatory Bowel Disease in the Southwest region of the Netherlands
Authors: Visser E , Allers S , van Linschoten R , Bodelier A , Fitzpatrick C , de Jong V , Vermeulen H , Verweij E , van der Wiel S , van der Horst D , van der Woude C J , van Noord D , West R L ,   Southwest Netherlands IBD Study Group
Published: January 2025

Abstract

Background
In the southwest of the Netherlands, there is a close collaboration between hospitals to improve care for inflammatory bowel disease (IBD). This collaboration aims to deliver high quality and uniform care across the region. To achieve this, a care pathway (CP) was developed and implemented for treating IBD with biologics and small new molecules. The CP consists of subsets that address initiation and switching of therapy, frequency and type of follow-up. This study aims to assess adherence to the CP and determine barriers and facilitators of the development and implementation.

Methods
A mixed-methods study was conducted using quantitative data to evaluate the adherence to the CP per subset. Quantitative data was retrospectively collected from electronic medical records (EMR) from December 2020 until March 2023. Surveys and semi-structured interviews were used to identify barriers and facilitators, using the Extended Normalization Theory. Surveys were sent to all healthcare providers (HCPs) and interviews were conducted with gastroenterologists, IBD-nurses, healthcare assistants and IT-personnel.

Results
Adherence to the CP regarding the registration of discussed treatment options was 50%. Weight measurements ranged from 12% to 25% across different CP subsets. Smoking status and medication side effects were documented in respectively 30% and 33% of patients. Validated questionnaires were rarely used to record disease activity, with adherence rates between 6% and 20%. Only 25% of patients who started or switched biologics were screened for HIV, tuberculosis and hepatitis B and C. Outpatient visits were scheduled according to the CP in 67% to 75% across CP subsets. Blood tests were ordered as per CP, or an exemption was registered in 25% to 42%. Microbiology tests were ordered according to the CP in 52% of patients experiencing a flare. Of the 85 surveys distributed to HCPs 42 were completed and 11 interviews were conducted. Facilitators of the CP were improving collaboration between HCPs, the potential to standardise IBD care, and that the CP is user-friendly for HCPs. Barriers included the complexity of the implementation of the CP in EMR, the difficulty for HCPs to change their current routine, and the heterogeneity of IBD.

Conclusion
A CP for the treatment of IBD with biologics and small new molecules has been implemented to improve patient care, however, adherence appears to be challenging. Despite the barriers, the CP is well designed and offers sufficient flexibility to personalise care where necessary. A possible reason for the adherence results may be the limited registration in EMR by HCPs. This could be improved by audit and feedback sessions, to communicate current adherence and improve implementation in daily practice.
P0626 One year outcomes of upadacitinib in Crohn’s disease in a large real-world cohort
Authors: Ramos Belinchon C , Plevris N , Elford A , Gros B , Constantine-Cooke N , Arnott I D , Lees C W 
Published: January 2025

Abstract

Background
Upadacitinib (UPA) was approved in April 2023 for the treatment of moderate and severe active Crohn’s disease (CD) by European and UK regulators (EMA / MHRA). Current real-world datasets are limited by small size and short follow-up. We aimed to evaluate the long-term outcomes of UPA in a real-world cohort.

Methods
We performed a retrospective cohort study, including all CD patients commenced on UPA from October 2022 to July 2024 in Lothian, Scotland. Detailed patient phenotyping and laboratory data were extracted from the Electronic Health Records (TRAKCare). Our primary outcome was treatment persistence at 12 months. Our secondary endpoints were persistence at 6 and 18 months and the reduction in Harvey Bradshaw Index (HBI), C reactive protein (CRP) and faecal calprotectin (FC). Adverse events were recorded

Results
We included 126 patients, with a median follow-up time of 52.5 weeks (IQR, 36-80 weeks). Baseline characteristics of our population are shown in Table 1. Of the cohort, 96.8% had previously been exposed to any advanced therapy with 60.3% refractory to three or more advanced therapies. The cumulative survival on drug was 81.5%, 68.8% and 54.2% at 6, 12, and 18 months (Figure 1). Reasons for treatment cessation included primary non-response 18.3% (23/126), secondary loss of response 6.3% (8/126) and adverse events 7.9% (10/126). There was a significant reduction in HBI and FC after 12 months (Figure 1). During the maintenance period, 23 patients (18.3%) required hospitalisation as a result of a CD flare, 8 patients (6.3%) underwent CD related surgery and 3 (2.4%) developed a perianal complication. Ninety nine adverse events were reported in 67 patients (54.9%), 11 of them (12.3%) experienced severe adverse events. The most common adverse events during follow-up were infection (23/126) and acne (22/126).

Conclusion
Upadacitinib persistence of almost 70% was observed after 12 months treatment in a highly refractory cohort of CD patients.
P0627 Pharmacokinetics, Pharmacodynamics, Safety, and Efficacy of Oral Resolvin E1-based Therapy in Inflammatory Bowel Disease (IBD): Translating Resolvin E1 Activation of BLT1 in Experimental Models to Healthy Volunteers
Authors: Danese S , Siegmund B , Peyrin-Biroulet L , Verstockt B , Dubinsky M , Newman R , Thomas H , Guttendorf R , Lipper R , Steinberg J , Paperiello B , Jennings T , Jordan D , Parkinson J , Mathias G , Sands B 
Published: January 2025

Abstract

Background
Resolvin E1 (RvE1), an endogenous lipid mediator, shows efficacy in murine colitis models by modulating mucosal immunity and protecting epithelial barrier function. RvE1 and leukotriene B4 (LTB4) are both BLT1 receptor agonists but elicit distinct biological outcomes through biased agonism. LTB4, a pro-inflammatory lipid mediator, initiates and regulates inflammatory responses by stimulating recruitment and activation of immune cells. In contrast, RvE1 selectively engages BLT1 to promote immune homeostasis and repair. TP-317, a stabilized RvE1 molecule, is being investigated as oral therapy for inflammatory bowel disease (IBD). In a sub-chronic murine model of DSS colitis, oral TP-317 (4.0 mg/kg) significantly improved disease activity and histological scores for mucosal inflammation and crypt loss. GLP toxicology studies in rats and dogs support TP-317’s safety profile, with the highest RvE1 doses tested in both preclinical species determined to be the no observed adverse event levels (NOAEL). This Phase 1a clinical study describes the pharmacokinetics (PK), pharmacodynamics (PD) and safety profile of TP-317 given as an enteric-coated tablet to healthy volunteers.

Methods
Twenty-four subjects were randomized 3:1 to single oral doses of TP-317 at 10, 40 and 80 mg (n=8/group). Safety, tolerability and PK/PD were assessed using standard methods. Subjects receiving the 80 mg dose underwent frequent CBC testing to assess short-term fluctuations in circulating neutrophils.

Results
Oral TP-317 was well tolerated, producing peak plasma RvE1 concentrations exceeding the EC50 for BLT1 activation (~10 nM) by 1.2, 2.8, and 6.7 times at 10, 40, and 80 mg doses, respectively. The mean AUC of the 80 mg group met regulatory requirements when compared to NOAEL dose exposures in rats and dogs. All 80 mg subjects experienced transient neutropenia, with neutrophils dropping below 1500/mL near RvE1 peak, followed by complete recovery above normal within ~2 hours. A similar pattern was previously observed without safety concerns in healthy subjects receiving an RvE1 drug at 150 mg twice daily for 10 days.

Conclusion
TP-317 demonstrates good tolerability and achieves adequate systemic RvE1 levels to engage the BLT1 receptor, offering a novel agonist approach to the LTB4-BLT1 pathway. Transient neutropenia observed with TP-317, a known effect of BLT1 activation by LTB4 and RvE1, suggests target engagement in humans. Oral TP-317’s safety profile and unique pro-resolution, barrier-protective mechanism warrant further clinical studies in IBD patients.
P0630 Are women with inflammatory bowel disease at risk of abnormal cervix cytology? -results of retrospective study
Authors: Tulewicz-Marti E , Lewandowski K , Karłowicz K , Maciejewska K , Sierakowska I , Szweda H , Rydzewska G 
Published: January 2025

Abstract

Background
Data regarding on CIN (cervical intraepithelial neoplasia) in IBD are conflicting, however it is considered that women with inflammatory bowel disease (IBD) may be at higher risk for CIN, especially in immunocompromised individuals. The aim of this study was to assess the prevalence of abnormal cervix cytology in IBD patients.

Methods
Retrospectively we have analysed digital data in patients with IBD what is more receiving immunosuppressive, small molecules or/and biological treatment.

Results
Results from the cervical cytologies were available from 301 IBD patients (150 with Crohn’s disease (50,3%), 151 with ulcerative colitis (49,8%)). The average age was 36.96±11.92 years for CD patients vs. 43.19±14.42 years for UC patients, MD = -6.23 CI95[-9.23;-3.23]. The average age at IBD diagnosis was 26.32±11.60 years for CD patients vs. 32.14±14.24 years for UC patients, MD = -5.82 CI95[-8.78;-2.87]. Comparing the data, no significant difference was however confirmed for disease duration between both groups. There were also no remarkable differences between both groups for: smoking status, current and past exposure to immunosuppressive drugs and frequency of gynecological control. Frequency of taking biological molecules currently was 88.0% for CD patients vs. 74.2% for US patients, OR = 2.55 CI95[1.36;5.01], p = 0.003. In the past 30.7% and 31.1% of patients in both groups respectively were taking biologics or small molecules (p &gt; 0.999). Deviations from norm in last cytology were identified in 5 patients from CD group (3.8%) vs. 1 patient in UC group (0.8%), OR = 5.17 CI95[0.57;247.51], p = 0.120. Deviations from norm in the last cytology or in the past referred 14 patients from CD group (10.3%) vs. 11 patients in UC group (7.7%), OR = 1.34 CI95[0.54;3.41], p = 0.621.
There was also noteworthy relationship between occurrence of deviations from norm in cytology and type of currently taken immunosuppressives (AZA vs. MP/MTX). Frequency of deviations from norm in last cytology was 10.0% of AZA patients vs. 6.2% of MP/MTX patients OR = 1.68 CI95[0.03;19.77], p = 0.521. For deviations from norm in last cytology or in the past respective numbers were: 10.0% and 9.9%, OR = 1.02 CI95[0.02;9.62], p &gt; 0.999.

Conclusion
In our cohort women with IBD are not at increased risk for cervical dysplasia, also in patients receiving immunosuppressive medication, small molecules or biological treatment. It may be related to regular gynaecological controls. More data especially regarding HPV infection is needed to know this problem better.
P0647 Impact of Age and Comorbidities on Treatment Outcomes and Mortality in Patients Admitted for Ulcerative Colitis Flares: A 20-Year Retrospective Cohort Study
Authors: Tejero Jurado R , el Fallous el Mraghid M , Carrillo Cubero B , Alañón Martínez P , Marín Pedrosa S , Soto Escribano P , Benítez Cantero J M , Iglesias Flores E M , Gros Alcalde B ,   Maimonides Institute for Biomedical Research at Cordoba
Published: January 2025

Abstract

Background
Approximately one-fourth of patients with inflammatory bowel disease (IBD) are aged 60 or older, increasing the challenge of managing disease-related comorbidities compounded by age-related conditions. This study aims to explore the influence of age and comorbidities on response to first-line and rescue therapies, need for surgery, and mortality in the context of UC admissions.

Methods
This is a retrospective cohort study including all patients hospitalized for ASUC from 2003 to 2023 at the Reina Sofía University Hospital. Participants were grouped by age (&lt;60 years, ≥60 years). We analyzed baseline characteristics, severity at admission, steroid response, complications, treatment intensification, need for colectomy, and mortality.

Results
A total of 419 patients were hospitalized for UC flares, with 19.6% (n=82) being elderly (≥60 years). Comorbidity (Charlson index ≥2: 42.7% vs. 7.3%, p&lt;0.0001) and polypharmacy (61% vs. 10.4%, p&lt;0.0001) were more frequent among older adults, Table 1. Regarding UC, no significant age-related differences were observed in disease extent or severity at admission (clinical, biochemical, or endoscopic parameters). Complications during hospitalization and corticosteroid response on days 3 and 5 were also similar across age groups. However, older patients showed lower rates of treatment intensification (41.7% vs. 55.7%, p=0.021), reduced access to biologicals anti-TNF agents or cyclosporine (13.1% vs. 26.3%, p=0.011), higher ICU admission rates (2.4% vs. 0.3%, p=0.044), greater readmission rates (28.9% vs. 16.9%, p=0.013), higher colectomy rates (32.1% vs. 17.4%, p=0.003), and increased one-year mortality following hospitalization (11.9% vs. 0, p&lt;0.0001). In multivariate analysis, advanced age remained a significant predictor for limited access to rescue therapies, Table 2.

Conclusion
In our study, older patients hospitalized for UC exhibited similar clinical characteristics regarding flare severity and corticosteroid response compared to younger patients. However, this subgroup had higher colectomy rates, ICU admissions, readmissions, and one-year mortality, along with reduced access to rescue therapies, including anti-TNF agents and cyclosporine.