bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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

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

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

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 > 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 > 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

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 (<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<0.0001) and polypharmacy (61% vs. 10.4%, p<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<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.
P0657 Quality of ileocolic resection in Crohn’s disease- A systemic review and meta-analysis
Authors: Lingam G , De Burlet K , Shakir T , Khattab M , Yiu A , Giannarou S , Francis N , Sahnan K
Published: January 2025

Background

The terminal ileum is the most common site affected by Crohn’s disease and the area most commonly requiring surgical management. Post operatively, there is large heterogeneity between patient outcomes; with a proportion requiring no further medical or surgical management, whilst others will require life-long management with repeated operations. The reason for this remains unclear.

Surgical key performance indicators for an ileocolic resection can include: recurrence, rate of anastomotic leak, post-operative complications (Clavien Dindo (CD) >3), length of stay, re-admission rate and mortality.

The aim of this study was to evaluate the effects of mode of surgery, the extent of mesenteric excision and the type of anastomosis on the rate of recurrence.

Methods

A systematic review was conducted following a priori protocol. Covidence software was used to exclude duplicates, screen studies and extract data. Extracted data was analysed. The primary outcome was recurrence rate and the mode of detection. Secondary outcomes were; anastomotic leak, post-operative complications (CD >3), length of stay, readmission rate, mortality and duration of follow up. Combined overall effect size was calculated using SPSS software. The revised Cochrane risk of bias tool and the Newcastle-Ottawa scale were used to assess risk of bias.

Results

A total of 24 studies were included. Four (three randomised controlled trials (RCTs)) in the mode of surgery group, four in the extent of mesenteric resection group and sixteen (two RCTs) in the type of anastomosis group. In all four studies included in the mode of surgery group, laparoscopic surgery was associated with a shorter length of stay. No difference was observed in the other outcomes, including rate of recurrence. There was no significant correlation between extended versus limited mesenteric excision and the rate of recurrence (p0.307, OR 0.61 (CI95% -.056, 1.77)). Four studies compared Kono-S anastomosis versus non-Kono-S anastomosis. Kono-S anastomosis was associated with a significantly lower recurrence rate (p=0.002, OR 0.62 (CI95% 0.24, 1.01)). There was significant heterogeneity between these studies (p<0.001).

Conclusion

To date there is no convincing evidence that the mode of surgery, the extent of the mesenteric excision or the type of anastomosis have any significant effect on reducing the occurrence of Crohn’s recurrence at the anastomosis.

References

N/A
P0660 Comparative Accuracy and Reliability of Handheld versus Cart-Based Ultrasound in assessing Inflammatory Bowel Disease Activity
Authors: Khaing M M , Fernandes R G , An Y K , Baraty B , Bryant R V , Ghaly S , Smith R L , Srinivasan A , Hay K , Begun J
Published: January 2025

Background

Bowel wall thickness (BWT) and vascularity are key parameters for assessing inflammatory bowel disease (IBD) activity. Handheld ultrasound devices (HHUS) provide a portable and affordable alternative for incorporating intestinal ultrasound (IUS) into IBD management. However, their diagnostic accuracy and reliability compared to cart-based ultrasound (CBUS) remain uncertain. This study assesses the diagnostic accuracy, reproducibility, and practitioner confidence with HHUS in comparison to CBUS for assessing BWT and vascularity.

Methods

In this prospective, comparative study, 12 patients with IBD, with body mass index (BMI) <23 kg/m², were assessed. Each patient underwent ultrasound scanning of 2–3 pre-specified bowel segments using five devices: one CBUS device (Samsung™) and four HHUS devices (Clarius™ L15 HD3, GE™ Vscan Air CL, Mindray™ TE Air, and Philips™ Lumify L12-4). Linear probes were used for all devices except Mindray™, which employs a phased array probe optimised for cardiac imaging. Scans were conducted by two to three gastroenterologists accredited by the Gastroenterology Network of Intestinal Ultrasound (GENIUS), who were blinded to each other’s findings to reduce bias. BWT and Doppler vascularity, as well as other standard IUS parameters, were assessed for each segment. Diagnostic accuracy and inter-/intra-expert agreement were analysed using statistical models.

Results

Among the 12 patients (42% male; median age: 26 years, IQR: 23–36) with CD (n=6) and UC (n=6), a total of 29 bowel segments were assessed with all devices (Table 1). BWT measurements showed high concordance across devices for active segments (mean BWT: 4.3–4.6 mm, p=0.73). However, significant discrepancies were noted in inactive segments (p<0.001), particularly with the Mindray™ device showing larger deviations from the CBUS measurements. Intraclass Correlation Coefficients (ICC) for intra-expert BWT measurements were good to excellent across devices (ICC 0.79–0.97), while inter-expert agreement was good for all devices (ICC 0.70–0.77) except for Mindray™ (ICC 0.36) (Figure 1B). Significant confidence was noted for BWT, vascularity, stratification, mesenteric fat, and inflamed bowel length across devices, highlighting consistent measurement reliability for these parameters (Table 1).

Conclusion

The majority of HHUS devices used in this study demonstrate high diagnostic accuracy and reproducibility in assessing IBD activity and are comparable to CBUS for identifying and assessing active disease. This study supports the integration of HHUS into IBD management as a portable and accessible tool while highlighting the importance of recognising device-specific limitations when selecting devices for clinical practice.
P0661 Effectiveness of upadacitinib for induction of remission in moderate-to-severe ulcerative colitis: real-world clinical outcomes appear independent of prior tofacitinib exposure
Authors: Elosua Gonzalez A , Zabalza L , Vicuña M , Rubio S , Nantes Ó , Rodriguez C
Published: January 2025

Background

Upadacitinib (UPA), a selective JAK1 inhibitor, has shown efficacy in clinical trials for moderate-to-severe ulcerative colitis (UC), but real-world data remain limited, particularly on outcomes related to prior exposure to other JAK inhibitors, such as tofacitinib (TOFA). This study evaluates real-world outcomes of UPA induction therapy in UC, focusing on clinical remission and differences by prior TOFA exposure.

Methods

This retrospective, observational study was conducted at a tertiary care centre in Spain, including adult patients with moderate-to-severe UC who initiated UPA in routine clinical practice. Data were retrospectively collected from electronic records, capturing baseline characteristics, TOFA exposure, disease duration, and concomitant treatments. The primary outcome was clinical remission at end of induction, assessed via the Physician Global Assessment (PGA) based on symptoms and laboratory data. Secondary outcomes included changes in faecal biomarkers, adverse events, treatment discontinuation, and maintenance dosing.

Results

Twenty-six patients were included, with a mean age of 50.5 years, 61.5% female, and a median disease duration of 10 years. All patients had prior exposure to advanced therapies, with 53.8% treated with at least three different lines of therapy. TOFA-exposed patients had a higher rate of pancolitis (84.6% vs. 30.8%; p=0.013), though endoscopic severity was similar between groups. All patients began with 45 mg UPA once daily; 23% had concomitant treatments, including vedolizumab (n=1), apheresis (n=3), and prednisone tapering (n=2).

Following induction, 65.4% achieved clinical remission and 88.5% at least a partial response based on PGA. Among TOFA-naïve patients, 76.9% achieved remission and 100% partial response, compared to 53.8% and 76.9%, respectively, in TOFA-exposed patients (p=0.9). Faecal calprotectin levels decreased, with reductions of 96.7% in TOFA-naïve patients (from median 4002 µg/g to 132 µg/g) and 97.9% in TOFA-exposed patients (from 3556 µg/g to 76 µg/g).

Extended induction was needed in 38.4% of patients, with no difference based on prior TOFA exposure (46.2% vs. 30.8%, p=0.6). Discontinuation during induction occurred in 23%, due to lack of effectiveness in 50%, adverse events in 33%, and transition to vedolizumab monotherapy in 17%. Post-induction, 88.4% continued on 30 mg as maintenance, consistent across both groups.

Conclusion

UPA induction therapy shows promise in achieving clinical remission in moderate-to-severe UC, with comparable outcomes independent of prior TOFA exposure. Our data suggests UPA may be a valuable option in real-world, treatment-experienced UC populations. Further studies could help clarify its role in complex cases and refine treatment strategies
P0663 Efficacy and safety of risankizumab therapy in Chinese patients with moderately to severely active crohn’s disease
Authors: Gao X , Cao Q , Ran Z H , Chen Y X , Chen Y , Wen Z H , Liu D L , Ding J , Zhong J , Liu F , Sha W H , An P , Wang B M , Hu L X
Published: January 2025

Background

Risankizumab (RZB) is an interleukin 23p19 inhibitor approved for adults with moderately to severely active CD. In phase 3 trials, greater proportions of patients with CD achieved clinical remission and endoscopic response with RZB therapy vs placebo (PBO). This post hoc subanalysis evaluates the efficacy and safety of RZB therapy in Chinese patients from the induction and maintenance studies.

Methods

ADVANCE and MOTIVATE were randomized, double-blind, PBO-controlled, phase 3 induction studies. Patients with intolerance/inadequate response to biologic and/or conventional therapy were randomized to receive intravenous (IV) RZB (600 or 1200 mg) or PBO at weeks 0, 4, and 8. Clinical responders to IV RZB could enter the phase 3, randomized, double-blind, PBO-controlled maintenance withdrawal study (FORTIFY). Patients were rerandomized to receive subcutaneous (SC) RZB (180 or 360 mg) or PBO (withdrawal) every 8 weeks for 52 weeks. Stool frequency (SF)/abdominal pain score (APS) clinical remission (average daily SF ≤2.8 plus average daily APS ≤1, and both not worse than induction baseline) and endoscopic response (>50% decrease in Simple Endoscopic Score for Crohn’s Disease [SES-CD] from baseline [or ≥2-point reduction from baseline for patients with isolated ileal disease and a baseline SES-CD of 4]) were evaluated.

Results

This analysis evaluated 75 Chinese patients in the induction studies. Demographic and baseline disease characteristics were generally similar across treatment groups (Table 1).At week 12 of induction, a numerically greater proportion of patients treated with RZB compared with PBO achieved, with percentages of 56.7% and 53.3% for the RZB 600 mg group, 64.7% and 44.1% for the RZB 1200 mg group, and 27.3% and 18.2% for the PBO group, respectively (Figure 1).

Among the 50 patients who entered the maintenance study, a numerically greater proportion of patients treated with RZB compared with PBO achieved SF/APS clinical remission and endoscopic response at week 52. with percentages of 73.3% and 66.7% for the RZB 180 mg group, 83.3% and 72.2% for the RZB 360 mg group, and 64.7% and 41.2% for the PBO group, respectively.

Similarly, at both week 12 and week 52, patients in the RZB groups achieved numerically greater proportions of Crohn’s Disease Activity Index (CDAI )clinical remission, CDAI clinical response, and endoscopic remission compared to the PBO group.RZB IV and SC doses were well-tolerated in the Chinese patients.

Conclusion

Consistent with global population results, Chinese patients with moderately to severely active CD treated with RZB achieved clinical and endoscopic outcomes at higher rates than did patients receiving PBO, with a tolerable safety profile.

References

1. D’Haens G, et al. Lancet. 2022;399:2015–30. 2.Ferrante M, et al. Lancet. 2022;399:2031–46.
P0668 Is there a “Weekend Effect” on clinical outcomes in acute severe ulcerative colitis? A single centre retrospective analysis
Authors: Mohamedrashed M , Yogakanthi S , xu C , Bartlett R , Chew M , Nedumannil L , Lucas S , Chauhan A , Lewis D , Kashkooli S , Garg M
Published: January 2025

Background

Acute severe ulcerative colitis (ASUC) represents a medical emergency that requires hospitalisation, close monitoring and intensive medical therapy. The “weekend effect” refers to the observed phenomenon of poorer patient outcomes when admitted over the weekend compared to weekdays. This study aimed to examine this phenomenon in patients admitted with ASUC.

Methods

Patients admitted with ASUC between January 2016 to October 2024 were identified retrospectively. Patient characteristics and clinical outcomes were accessed from the electronic medical records (EMR). Outcomes analysed included length of hospitalisation, time to first endoscopic assessment, requirement for rescue therapy, time to rescue therapy, rate of colectomy, and 12-month readmission rate. Weekday admissions were defined as Monday-Thursday, with weekend admissions Friday-Sunday.

Results

141 patients (56% male; median age 34 [IQR 25-49] y) fulfilling Truelove and Witts’ criteria were included in this study. 105 (74.5%) were admitted on weekdays, and 36 (25.5%) on weekends. Baseline characteristics of both groups are outlined in Table 1.

The median length of initial hospitalisation was 138 (IQR 95-174) hours in patients admitted on weekdays compared with 167 (IQR 129-263) hours in those admitted on weekends (p = 0.02). The time to first endoscopic assessment was 30 vs 62 (p = 0.05) hours in those admitted on weekdays vs weekends, respectively. Rescue therapy with infliximab was required in 60 (57.1%) vs 24 (66.6%) patients (p = 1.0), respectively. The median time for infliximab therapy was 82 (IQR: 52.5-116) hours in the weekday vs 99 (IQR: 75-149) hours in the weekend group (p = 0.02). On multivariate analysis, weekend admission, as well as baseline characteristics and intervention timings, did not significantly predict length of stay. There was no statistically significant difference in the requirement for colectomy (6 vs 1 patients, p = 0.68).

Twelve-month all-cause readmission rates were similar for both weekday and weekend admission groups (33/105 [31.4%] vs 12/36 [33.3%], p = 0.83), including both UC-related (weekday 17/105 [16.1%] vs. weekend 8/36 [22.2%], p = 0.66), and non-UC-related (weekday 16/105 [15.2%] vs. weekend 4/36 [11.1%], p = 0.18).

Conclusion

Patients admitted to hospital with ASUC on weekdays had a significantly shorter length of stay, time to endoscopy assessment, and time to rescue infliximab therapy. No significant differences in other outcomes were noted. Improved access to endoscopic assessment and infliximab rescue therapy may reduce length of stay, improving resource utilisation.
P0669 Safety of intravenous and subcutaneous guselkumab induction administration: Results from the GALAXI and GRAVITI studies in participants with Crohn’s Disease
Authors: Danese S , Sands B E , Afzali A , Hisamatsu T , Armuzzi A , Wolf D , Duvall G , Van Rampelbergh R , Olurinde M , Terry N A , Yee J , Li H , Rosas Ballina M , D’Haens G , Rubin D T , Panaccione R
Published: January 2025

Background

Guselkumab (GUS) is a dual-acting IL-23 inhibitor that potently neutralizes IL-23 and binds to CD64, a receptor on cells that produce IL-23. Induction with both intravenous (IV) and subcutaneous (SC) GUS was effective in phase 2/3 clinical trials of participants (pts) with moderately to severely active Crohn’s disease (CD). To characterize the safety of GUS IV and SC induction regimens, we evaluated safety data from clinical trials of GUS in CD.

Methods

We evaluated data from phase 2/3 CD studies with IV induction (GUS 200mg IV q4w in GALAXI 1, 2, and 3) and SC induction (GUS 400mg SCq4w in GRAVITI) to assess rates of safety events (proportions of pts with ≥1 event) during the induction period (Week 0-12).

Results

During the induction period, rates were not higher in either the IV or the SC groups than the respective placebo (PBO) groups for adverse events (AEs), serious AEs, or AEs leading to discontinuation (Table 1). Serious infections occurred in 1 pt in the GUS IV group and 1 pt in the GUS SC group; neither led to discontinuation of study treatment. No serious infections were reported in PBO-treated pts in either group.

Of the 1376 GUS SC injections during the induction period in GRAVITI, 6 (0.4%) were associated with injection site reactions, which included pruritus, erythema, and swelling. Injection site reactions beyond the induction period with GUS SC in GALAXI and GRAVITI remained low (≤1%) and were comparable regardless of induction administration route.

No cases of active tuberculosis, anaphylaxis, serum sickness reactions, major adverse cardiovascular events, or venous thromboembolism were reported during the induction period. In the IV induction group, 1 opportunistic infection (esophageal candidiasis) was reported in a PBO-treated pt and 2 were reported in GUS-treated pts (cytomegalovirus infection and esophageal candidiasis). In the SC induction group, 1 opportunistic infection of esophageal candidiasis was reported in a PBO-treated pt and 0 were reported in GUS-treated pts. One malignancy (basal cell carcinoma) not leading to discontinuation was reported in a pt in the GUS 400 mg SC group. One death was attributed to a non-suicidal (not self-inflicted) gunshot wound in a pt treated with GUS SC.

Clinically significant hepatic disorders were reported in 2 pts in the GUS 200mg IV group (1 SAE and 1 AE that led to discontinuation) and 1 pt in the GUS 400mg SC group (1 AE that led to discontinuation) during the induction period. All cases were confounded by additional diagnoses or concomitant medications.

Conclusion

Both IV and SC induction demonstrated comparable safety results consistent with the well-characterized GUS safety profile. No new safety concerns were identified.
P0675 Ultrasonographic assessment of response in hospitalized patients with acute severe ulcerative colitis
Authors: Arora U , Kandasamy D , Verma M , Madan D , Singh M , Narang H , Goyal M , Mubunnu M , Panwar R , Dash N R , Goyal A , Sharma R , Ahuja V , Kedia S
Published: January 2025

Background

Patients admitted with acute severe ulcerative colitis (ASUC) respond to medical therapy in upto two-third cases but monitoring and early detection of non-response is of prime importance to prevent colectomy or mortality, through use of rescue medical therapy. This study evaluates the utility of ultrasonography (USG) in prognostication and decision-making for ASUC patients undergoing standardized treatment protocols. USG offers a non-invasive approach to assess bowel wall thickening and vascularity, pivotal indicators of disease activity.

Methods

In this prospective study, 45 ASUC patients undergoing intravenous steroid therapy were enrolled, with additional randomization to receive tofacitinib or placebo. USG evaluations of bowel wall thickness (defined as ≥3 mm) and vascularity were conducted at baseline and on day 5, with data available for 41 patients. Clinical responses were assessed using the Lichtiger index. Correlations between USG findings, clinical outcomes, and biochemical markers such as CRP and albumin were analyzed.

Results

Baseline USG revealed bowel wall thickening in the sigmoid colon in 82.9% (34/41) of patients and in the descending colon in 70% (28/41). (Figure 1)

Responders showed a significant reduction in bowel wall thickness in the sigmoid and descending colon (p < 0.05), whereas non-responders exhibited no changes. (Figure 2)

There was a moderate correlation between bowel wall thickening across different segments (Spearman’s rho = 0.3–0.5, p < 0.05), but no significant correlation with CRP, albumin, or endoscopic severity. Doppler findings indicated similar rates of increased vascularity (Limberg grade ≥3) in both responders and non-responders at baseline and follow-up. Ancillary findings, such as pericolic fat thickening and free fluid, were associated with poor clinical outcomes, highlighting their prognostic value. Notably, baseline USG identified skip lesions in two patients, later confirmed to have Crohn’s colitis instead of ASUC. The sample size was limited as the trial is ongoing, and the treatment groups (tofacitinib vs. placebo) remain blinded.

Conclusion

Serial ultrasonography of the left colon provides valuable, non-invasive insights into treatment response in ASUC, correlating well with reductions in clinical activity and bowel wall thickness among responder. Presence of pericolic fat thickening and ascites correlates with poor outcomes, while doppler assessment does not contribute to the assessment. Importantly, baseline USG may aid in differentiating ASUC from Crohn’s colitis in patients with index presentation as acute severe colitis.
P0679 Therapeutic Drug Monitoring of the Infliximab (anti-TNF) Level with Bedside Kit in Inflammatory Bowel Disease
Authors: Gur M B , Bakkaloglu O K , Eskazan T , Akpinar A , Hatemi A İ , Erzin Y Z , Celik A F
Published: January 2025

Background

Approximately half (10-40%) of the Inflammatory Bowel Disease (IBD) patients using Infliximab (IFX) develop secondary loss of response due to drug levels falling below the therapeutic range. This study aims to identify drug levels, influencing factors and parameters that may be useful in predicting target drug levels.

Methods

The pre-infusion drug levels and associated laboratory parameters were evaluated in IBD patients on maintenance dose of IFX (5-15 mg/kg every 4-8 weeks) between Nov2021 - Oct2024. Drug levels were measured using a bedside kit capable of quantitatively detecting values between 0.4-20 µg/ml.

Results

In total, 931 single pre-infusion measurements from 415 different patients, and dual measurements at weeks 4 and 8 from 116 patients were separately evaluated. 82% of the patients in the single measurement group, and 84% in the double measurement group had Crohn’s disease(CD), rest having Ulcerative Colitis. The most used doses in the single measurement group were 5 mg/8 weeks and 10 mg/4 weeks (Table 1). In the single measurement group, median albumin was 4.4 (IQR: 0.5), and median CRP was 3.1 (IQR: 6.4). Drug levels were below 5 µg/ml in 33% of measurements. CRP showed a significant difference according to drug level groups (Table 2), while no such difference was observed for albumin. In the measurable IFX range (0.4-20 µg/ml), correlation analysis revealed a weak negative correlation between CRP and drug levels (r: -0.09, p: 0.03). Regression analysis showed that lower CRP, higher drug dose, and CD diagnosis were independently associated with achieving >5 µg/ml drug levels. In the dual measurement group: The median CRP levels of patients at weeks 4 and 8 were 2.1 (5.1) and 2.6 (6.2), respectively (p>0.05). Among patients with IFX levels >20 µg/ml at week 4, 79% maintained levels >5 µg/ml at week 8, while this rate dropped to 71% for those with levels >10 µg/ml. Only 67% of patients with levels >5 µg/ml at week 4 maintained a level of >5 µg/ml at week 8 (all p-values <0.001).

Conclusion

As drug levels increase, significant reductions in CRP levels are observed. Therefore, low CRP levels may predict the likelihood of achieving the therapeutic range. Dose adjustment should be considered in cases with high CRP levels. Achieving a high drug level (>20 µg/ml) at 4th week is an important indicator of achieving at least an acceptable drug level (>5 µg/ml) at the end of treatment. (8th week).
P0681 Filgotinib for active Ulcerative Colitis in clinical practice - Effective treatment at week 8 is associated with higher clinical remission and persistence rates at Week 52 -
Authors: Yamada A , Yokoyama K , Harada Y , Ito T , Horii T , Kanazawa J , Ikehara H , Kusano C
Published: January 2025

Background

There are few reports on therapeutic outcomes one year after starting filgotinib (FIL), a novel JAK inhibitor for ulcerative colitis (UC) in clinical practice. We studied the therapeutic outcomes and safety of FIL at 52 weeks after its initiation.

Methods

This is a single-centre retrospective study including 60 patients whose partial Mayo Score (pMS) was ≥2 and whom we were able to follow up for eight weeks or more in our centre after the start of FIL. The primary endpoint was the clinical remission rate at Week 52, the secondary endpoints were the clinical response rate at Week 52, cumulative persistence rate of FIL at Week 52, clinical remission rate and response rate at Week 8 and adverse events. Treatment response and persistence were examined according to treatment history with biologics (BIO) and JAK, concomitant use of immunomodulators (IM), pMS at the start of FIL and clinical response at Week 8 after the start of FIL. Remission was defined as pMS≤1 and response as decrease of pMS≥2 from the start of FIL.

Results

Amongst the 60 patients who started FIL in our centre from Apr 2022 onwards, the median of pMS at the start of FIL was 5 (IQR 2-6), the mean treatment duration was 404±279 days. BIO/JAK naive cases were 48% (29/60), cases with concomitant use of prednisolone (PSL) were 23% (14/60), and the mean dosage was 8.5 mg/day. Cases with concomitant use of IM was 37% (22/60). The overall clinical remission rate at Week 52 was 56% (25/45), 72.2% in BIO/JAK naive cases and 44.4% in BIO/JAK experienced cases (p=0.07) (Fig 1a). It was 61.5% in pMS 2-6, and 16.7% in pMS≥7 (p=0.07) (Fig 1b), whereas there was no significant difference between concomitant use of IM and non-IM cases (Fig 1c). Compared to the non-response cases, the remission rate of clinical response cases at Week 8 after the start of FIL was significantly higher in the remission rate at Week 52 (70% vs 27%, p=0.01) (Fig 1d). The clinical response rate at Week 52 was 58% (26/45) and the remission rate and response rate at Week 8 were 42% (25/60) and 68% (41/60), respectively. The cumulative persistence rate of FIL at Week 52 was 74.4% (Figure 2a). The BIO/JAK naive cases showed a significantly higher persistence rate at Week 52 compared to the BIO/JAK experienced cases (86.8% vs 61.7%, p<0.05) (Figure 2b). The persistence rate at Week 52 of the clinical response at Week 8 cases was significantly higher than the non-response cases (85.9% vs 40.0%, p<0.05) (Figure 2c). There was one patient who discontinued FIL due to an adverse event of skin symptoms.

Conclusion

Both clinical remission rate at Week 52 and persistence rate of FIL were significantly higher in the cases that had response at week 8, compared to the non-response cases.
P0684 Real world experience with granulocyte and monocyte adsorptive apheresis (ADACOLUMN®) in patients with refractory inflammatory bowel disease: a retrospective observational multicenter cohort study
Authors: Hupé M , Bouguen G , Buisson A , Landman C , Uzzan M , Nancey S , Guillaume C , Cyrielle G , Charkaoui M , Serrero M , Wampach A , Collins M , Altwegg R , Cholet F , Amiot A
Published: January 2025

Background

Granulocyte and monocyte adsorptive apheresis (GMA) with ADACOLUMN® (JIMRO Takasaki Japan) is an effective and safe therapeutic option for patients with mild to moderate inflammatory bowel disease (IBD) refractory to pharmacological therapy, especially ulcerative colitis (UC). The aim of this study was to report effectiveness of GMA in patients with IBD.

Methods

All consecutive active, non-operated UC patients and Crohn’s disease (CD) patients treated with GMA in 15 French tertiary-care centres from 2007 to september 2024 were assessed. Patients received 4 to 8 weekly sessions of GMA alone or in combination with previously failing advanced therapy. Patients were assessed for effectiveness at week 14 and at week 54 for those continuing GMA as maintenance therapy and at every visit for safety. Clinical remission, steroid-free clinical remission, clinical response, colectomy as well as safety were ascertained.

Results

One hundred and twenty-nine patients with IBD (75 males, median age: 40.9 IQR[29.3-58.1] years, 102 with UC, IBD duration: 7.0 [2.9-13.1] years) were included. One hundred patients (77.5%) were previously treated with immunosuppressants and 97 (72.2%) with at least one anti-TNF. In patients with UC, baseline median total Mayo score was 7 [6-12] and mean CRP level was 23.3 ± 86.0 mg/L. In patients with CD, baseline median Harvey-Bradshaw index was 9 [7.25-10.75] and mean CRP level was 21.9 ± 27.3 mg/L. In patients with UC, week 14 clinical remission, steroid-free clinical remission and response rates were 33.3%, 27.5% and 52.0%, respectively. In patients with CD, week 14 clinical remission, steroid-free clinical remission and response rates were 33.3%, 29.6% and 66.7%, respectively. At week 14, nine patients with UC and 3 patients with CD required emergent surgery. At week 14, adverse events were reported in 26 (20.2%) and were mainly related to flare of IBD in 16 (12.4%). Other adverse events which were never classified as serious included headache in 3, arthromyalgia in 3 and abdominal pain, diarrhea, grade-1 increase in liver enzymes and mild hypotension in one. At week 54, 48 patients were still treated with maintenance GMA therapy including 13 with CD and 35 with UC. At week 54, steroid-free clinical remission rates were 38.5% (5/13) in patients with CD and 60% (21/35) in patients with UC.

Conclusion

In this real world cohort of patients with refractory IBD, GMA induced steroid-free clinical remission in one third of patients with CD and UC at W14. In patients continuing GMA maintenance therapy, steroid-free clinical remission was observed in one third of patients with CD and two thirds of patients with UC. Safety profile was favourable mostly related to relapse of IBD.