bluuebunny/crossref_metadata_2025 huggingface dataset:
P0786 The short-term efficacy of Filgotinib on antibiotic-dependent/resistant pouchitis in patients with ulcerative colitis
Authors: Uchino M , Ikeuchi H , Horio Y , Kuwahara R , Kusunoki K , Nagano K , Tomoo Y , Nomura K
Published: January 2025

Background

In surgeries for ulcerative colitis, total colectomy and ileal pouch-anal anastomosis are the standard procedures, but one of the postoperative issues is developing pouchitis. It is believed to be related to dysbiosis, and antibiotic therapy is often effective. However, antibiotic dependency/resistance is a problem in clinical practice, making treatment challenging. In this study, we aimed to evaluate the therapeutic effect of filgotinib on cases of antibiotic-dependent/resistant pouchitis.

Methods

We targeted cases of antibiotic-dependent/resistant pouchitis since July 2022. Antibiotic dependency was defined as cases where antibiotics could not be discontinued for more than 4 weeks or cases of relapse occurring 3-4 times per year, while antibiotic resistance was defined as cases that did not improve with 4 weeks of antibiotic treatment. Pouchitis was diagnosed using the modified Pouchitis Disease Activity Index (m-PDAI), with a score of 5 or more considered indicative of pouchitis. Treatment involved filgotinib at 200 mg/day, and during the first 2-4 weeks of treatment, concomitant use of antibiotics or local steroids was allowed. The endpoint was set as cases where clinical symptoms improved based on the m-PDAI, and CRP became negative 8 weeks after the start of treatment, with these cases being classified as responders.

Results

Ten patients received treatment. The male-to-female ratio was 7:3, with an average age of 44.6 ± 11.1 years and an average of 51 ± 44 months since pouch formation. Nine patients had antibiotic-dependent pouchitis, and one had antibiotic-resistant pouchitis. All patients were treated with ciprofloxacin at 600 mg/day, and two patients also received local steroids at the induction of filgotinib. After 8 weeks, six patients showed improvement in clinical symptoms and CRP negativity. Among the responders, the clinical symptom score of the PDAI decreased from 4.3 ± 0.2 to 1.7 ± 0.6 (P<0.01), and CRP levels decreased from 2.9 ± 0.6 mg/dL to 0.6 ± 0.3 mg/dL (P<0.01). No adverse events were observed in these series.

Conclusion

In the short term, about 60% of patients showed improvement with filgotinib treatment. Further investigation into long-term relapse rates, maintenance rates, adverse events, and the possibility of dose reduction for maintenance therapy is necessary.
P0787 A large-scale comparison of clinical response to IBD therapies in white and non-white ethnicities
Authors: Balarajah S , Martinez-Gili L , Alexander J L , Mullish B H , Perry R W , Li J V , Marchesi J R , Parkes M , Orchard T R , Hicks L C , Williams H R
Published: January 2025

Background

IBD phenotypes differ between non-White (NW) and White (WH) populations. Ethnic differences can influence the effectiveness of non-IBD medications, and IBD therapies differ by IBD phenotype. An unanswered question is whether IBD therapies are equally efficacious, with a similar side effect profile, for all ethnic groups. This multi-centre cohort study sought to compare the effectiveness and adverse events (AEs) of IBD therapies in WH and NW patients.

Methods

Phenotypic and outcome data were extracted from the UK IBD BioResource, a large-scale IBD database enrolling patients across the UK. Response and AEs to 5-ASAs, thiopurines, anti-TNFs and anti-integrins were assessed. Treatment effectiveness was defined as treatment persistence free of discontinuation or failure, and evaluated using Kaplan-Meier survival and Cox regression analysis. The risk of experiencing any AE (and individual AEs with a given treatment) was assessed using Cox regression analysis. Models were adjusted for sex, smoking status, IBD subtype, disease duration, disease location/extent, disease behaviour (CD), perianal disease (CD), co-morbidities, presence of extra-intestinal manifestations, age at commencing therapy, steroid and concomitant immunomodulator use, and the occurrence of an AE (in treatment response models).

Results

In total 27,433 patients were included [51.1% females; median age at diagnosis 30 years (IQR 21-43); 94.7% WH, 5.3% NW (71.3% South Asian)].

NW were diagnosed at a younger age, exhibited different disease phenotypes, and were younger at treatment initiation therapy than WH. However, no differences in treatment persistence between WH and NW were identified for all therapies analysed, in either CD or UC (Table 1). NW were at significantly increased risk of AEs when treated with thiopurines [HR 1.16 (95% CI 1.00-1.35), p=0.046] and a similar trend was observed for anti-TNFs [HR 1.25 (95% CI 0.99-1.56), p=0.057]; Table 2]. Specifically, NW were at increased risk of developing leucopenia [HR 1.66 (95% CI 1.10-2.42), p=0.01] and pancreatitis [ p=0.009] with thiopurines, and renal dysfunction with anti-TNFs [HR 2.33 (95% CI 1.11-4.38), p=0.02].

Conclusion

This is the first large-scale study focussing on ethnic differences in IBD treatment response. No differences were observed in treatment response, but we have shown that thiopurines are associated with increased risks of leucopenia and pancreatitis, whilst anti-TNFs are associated with a higher risk of renal dysfunction in NW patients. These findings underscore the importance of thorough pre-treatment risk assessment and patient counselling by clinicians, and the need for more diverse patient representation in research.
P0790 Effectiveness of Tofacitinib and Filgotinib as An Induction Therapy for Patients with Moderate-to-Severe Ulcerative Colitis: Real-World Comparison in Propensity Score-Matching Analysis
Authors: Yagi S , Fukui H , Ikenouchi M , Shiraishi T , Wakita M , Takagi Y , Sato T , Kawai M , Kamikozuru K , Yokoyama Y , Takagawa T , Tomita T , Shinzaki S
Published: January 2025

Background

There are few data comparing the efficacy and safety of each Janus kinase (JAK) inhibitors in ulcerative colitis (UC) patients. We aimed to compare the real-world effectiveness and safety of tofacitinib (TOF) and filgotinib (FIL) which are JAK inhibitors applied for induction therapy in patients with UC.

Methods

We investigated the medical records of all UC patients who received TOF or FIL treatment as induction therapy between May 2018 and October 2023. We next selected the moderate to severe UC patients who matched the following criteria: partial Mayo Score (PMS) ≥3 or PMS =2 and a rectal bleeding subscore ≥1. A clinical response was defined as a reduction in PMS of ≥2 from baseline, with a rectal bleeding subscore ≤1 or a decrease of ≥1 from baseline. A clinical remission was defined as PMS ≤2, each subscore ≤1 and a rectal bleeding subscore of 0. The primary outcome was the clinical response at week 8 after therapy induction. The secondary outcomes were clinical response and remission at weeks 8 in patients without clinical response at week 4 after TOF or FIL administration and the safety during observation period.

Results

We identified 230 patients with moderate to severe UC who received either TOF (n = 197) or FIL (n = 33). Using propensity score-matching (PSM), thirty-three patients in both the TOF and FIL groups were isolated. PSM analysis showed that the rates of clinical response gradually increased to 72.2% at 8 weeks in the TOF group, whereas it tended to decrease to 48.5% in the FIL group. The clinical remission rates increased from 2 (36.7% in both groups) to 8 weeks (63.6% in the TOF group vs 48.5% in the FIL group). The rates of clinical response were higher in the TOF group than in the FIL group at week 8 in patients who did not achieve a clinical response at week 4 (38.5% vs. 0%; P = 0.011). The rates of clinical remission were also higher in the TOF group than in the FIL group at week 8 in patients who did not achieve clinical remission at week 4 (50.0% vs. 16.7%; P = 0.046). At least 1 adverse event occurred in 106 of 197 (53.8%) of patients in the TOF group and 11 of 33 (33.3%) in the FIL group.

Conclusion

TOF, unlike FIL, has the potential to benefit from continued treatment even if the patients did not show a significant clinical response/remission at 4 weeks after induction.
P0791 Development and validation of a nomogram for predicting the short-term effectiveness of Ustekinumab in patients with moderate to severe Crohn's disease
Authors: Su T , Wu H , Zhi M , Yao J
Published: January 2025

Background

Ustekinumab (UST) is recommended as the first-line treatment for patients with moderate to severe Crohn's disease (CD). The effectiveness of certain patients, however, may be suboptimal and necessitate intensive treatment or modification of the treatment regimen. We sought to establish a nomogram model to predict the short-term effectiveness of UST in moderate to severe CD patients.

Methods

We established a derivation cohort comprising patients diagnosed with CD and treated with UST at the Sixth Affiliated Hospital of Sun Yat-sen University between May 2020 and July 2023. The patient data, including demographic and clinical characteristics as well as treatment details, were systematically collected. The achievement of clinical remission (Crohn's Disease Activity Index, CDAI < 150) after induction therapy was the endpoint observed during follow-up. Potential predictors were selected using the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. Multivariate logistic regression analysis was performed to develop a nomogram model. The predictive accuracy and discriminative power of the model were evaluated using Receiver Operating Characteristics (ROC) curves and calibration curves. Decision curve analysis (DCA) was employed to assess the clinical utility of the model.

Results

A total of 162 moderate to severe CD patients were included in the derivation cohort. Prognostic factors, including duration, body mass index (BMI), smoking, extraintestinal manifestations (EIMs), perianal lesions (P), history of Vedolizumab therapy, and albumin levels (ALB), were identified and included in the nomogram. The model showed good discrimination and calibration on internal validation based on the bootstrap method (C-index: 0.843, 95% confidence interval [CI]: 0.768-0.903). Moreover, DCA demonstrated that the nomogram was clinically beneficial.

Conclusion

Our model is a useful tool for accurately predicting the short-term effectiveness of UST in moderate to severe CD patients and aids clinicians in formulating personalized treatment plans.
P0796 Comparison of Disease Severity, Treatment, and Outcomes in Elderly and Younger Patients Hospitalized with Acute Severe Ulcerative Colitis (ASUC)
Authors: Ollech J , Lev Kolnik R , Dotan I , Yanai H
Published: January 2025

Background

Acute severe ulcerative colitis (ASUC) is a life-threatening complication that requires prompt and effective treatment. Disease severity, treatment approaches, and outcomes may differ between elderly patients (aged ≥60 years) and younger patients. This study aims to compare these factors in a cohort of hospitalized ASUC patients.

Methods

A retrospective cohort study was conducted including all patients admitted between 1/2018-12/2023, with ASUC who failed oral steroid therapy to Rabin Medical Center in Israel, a large tertiary referral center. Baseline disease severity was assessed using hemoglobin, albumin, and C-reactive protein (CRP). Treatments analyzed included the use of rescue therapies such as infliximab and calcineurin inhibitors for patients failing intravenous corticosteroid therapy. Outcomes such as colectomy and mortality associated with ASUC were recorded.

Results

158 patients met the inclusion criteria and were stratified into two groups: elderly patients (≥60 years, n=16) and younger patients (<60 years, n=142).Elderly patients had a mean age of 72.9 years compared to 32.1 years in younger patients. Baseline hemoglobin levels were similar between the two groups (11.7 g/dL in elderly vs. 11.8 g/dL in younger patients). Albumin levels were also similar in elderly patients (3.6 g/dL) compared to younger patients (3.8 g/dL) as were CRP levels (5.7 mg/dl vs 5.8 md/dl) respectively. The use of infliximab was less common in elderly patients (12.5%, n=2) compared to younger patients (24.6%, n=35). Calcineurin inhibitors (ciclosporin or tacrolimus) were used in only 1 elderly patient (6.25%) but were used in almost 15 % (n=19) of younger patients. No elderly patients underwent colectomy during admission, while 7.0% (n=10) of younger patients did. Mortality was higher in elderly patients, with a case fatality rate of 12.5% (n=2), compared to no reported mortality in younger patients.

Conclusion

Elderly patients hospitalized with ASUC had similar baseline disease severity but received less rescue therapies and had worse outcomes compared to younger patients, including a higher mortality rate. These findings suggest that while disease severity may be comparable across age groups, elderly patients may experience greater complications, underscoring the need for tailored treatment approaches in this population.
P0799 Efficacy and Safety of Dual Therapy for Refractory Inflammatory Bowel Disease in a Danish Cohort
Authors: Haase A M , Bendix M
Published: January 2025

Background

Patients with Crohn’s disease (CD) and ulcerative colitis (UC) may become refractory to monotherapy with biologics or small molecules. Dual therapy, combining biologics and small molecules, has been proposed for this challenging population. While awaiting randomized studies, real-world data on its efficacy and safety are crucial. This study contributes to the evidence on dual therapy in a Danish adult IBD cohort.

Methods

Medical records from May 2018 to May 2023 were reviewed for CD and UC patients undergoing dual therapy with biologics and/or small molecules in outpatient gastroenterology clinics at Aarhus University Hospital and Regional Hospital Randers. Patients treated for at least three months were included and followed until treatment discontinuation or the end of the study period. Patient characteristics, clinical outcomes, adverse events, and efficacy data were collected at baseline and follow-up.

Results

Seventy-four patients (47 with CD and 27 with UC) received a total of 79 dual therapies. The median duration of dual therapy was 488 days for CD and 412 days for UC. The most common combinations were adalimumab and ustekinumab in CD (46%) and adalimumab and vedolizumab in UC (35%). Clinical remission was achieved in 56% of CD patients and 62% of UC patients. Steroid-free follow-up was observed in 81% of CD patients and 52% of UC patients (Table 1).

In CD, dual therapy significantly reduced stool frequency, bloody stools, calprotectin levels, and Harvey-Bradshaw Index (HBI) scores. In UC, stool frequency, nighttime stools, abdominal pain, CRP, calprotectin, and Simple Clinical Colitis Activity Index (SCCAI) scores significantly decreased, while hemoglobin and albumin levels significantly improved. Serious adverse events (SAEs) occurred in 12% of UC patients and 14% of CD patients, consistent with prior studies of adult and pediatric cohorts [1, 2]. No UC patients required colectomy during the study period.

Conclusion

This retrospective study demonstrates a substantial rate of clinical remission and acceptable safety in refractory IBD patients receiving dual therapy. The findings highlight prolonged treatment duration, significant clinical improvements, and a manageable SAE profile. Dual therapy represents a promising approach for refractory and complex IBD, though the risk of SAEs must always be balanced against therapeutic benefits.

References

1.Dual Biologic or Small Molecule Therapy in Refractory Pediatric Inflammatory Bowel Disease (DOUBLE-PIBD): A Multicenter Study from the Pediatric IBD Porto Group of ESPGHAN.Inflamm Bowel Dis, 2024. 30(2): p. 159-166.

2.Dual Biologic or Small Molecule Therapy for Treatment of Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol, 2022. 20(3): p. e361-e379.
P0800 Efficacy of filgotinib in patients with ulcerative colitis refractory to prior biologics
Authors: Suarez A , Ruz Zafra P , Leo Carnerero E , Rojas Feria M , De la Cruz Ramírez M D , Rodríguez Pérez A Á , Villalba Moreno Á M , Trigo Salado C
Published: January 2025

Background

Filgotinib has shown promise for patients with moderate-to-severe Ulcerative Colitis (UC) who are refractory to prior biologics. Given the need for effective alternatives in this challenging patients, this study examines the efficacy of filgotinib in biologic-refractory patients.

Methods

An observational, descriptive, ambispective, single-center study of 29 patients with active UC who were started on filgotinib 200mg/24h between October 2018 and May 2024. Clinical and biochemical variables analyzed: partial Mayo Score (PMS), endoscopic evaluation, fecal calprotectin (FC) and the adjuvant treatment-free response (corticosteroids or apheresis) at weeks 8, 16, 26 and 52. Other variables were also measured: disease characteristics, previous biologic treatments and concomitant use of corticosteroids and immunomodulators.

Results

The median age was 43 (IQR 32-53) years, 45% were women. The median disease duration was 7 (IQR 3-14) years. One patient smoked at the beginning of treatment, and ten were ex-smokers. 45% had extensive colitis (E3, according to Montreal classification), and 55% had left-sided colitis. In 13 patients, colonoscopy was performed prior to drug initiation, with 92% presenting an endoscopic Mayo score 2-3.

The most unique feature of our cohort is the high refractoriness to previous biologic treatments. Only one patient was naïve to biologics, as he was not a candidate for anti-TNF due to a history of multiple sclerosis. Of the remaining 28 patients, the majority (97%) had failed anti-TNF treatment, 41% had also failed ustekinumab and 34% had failed vedolizumab. At the time of treatment initiation, 45% were receiving concomitant oral or intravenous corticosteroids.

In terms of baseline disease activity, the median PMS was 6 (IQR 5-7), and the median FC was 2000 (IQR 1664-2000) µg/g.

Median follow-up was 26 (8-52) weeks. At weeks 8, 16, 26 and 52, the clinical response (PMS reduction ≥2) and clinical remission (PMS ≤1) rates were 83%/45%, 80%/64%, 72%/56% and 62%/47%, respectively (image 1). There was a significant decrease in FC: 1124 (IQR 155-2000) µg/g, 860 (IQR 53-2000) µg/g, 187 (IQR 82-1107) µg/g and 165 (IQR 17-1910) µg/g at weeks 8, 16, 26 and 52, respectively. Adjuvant treatment-free response was 43% with an estimated Kaplan-Meier curve persistence of 48% at 1 year (image 2.1). During follow-up, filgotinib was discontinued in 7 patients, 4 of them in the first 8 weeks. Attached is the Kaplan-Meier curve for the persistence of Filgotinib (image 2.2) estimated at 72% at 1 year.

Conclusion

Filgotinib is effective in the treatment of biologic-refractory ulcerative colitis in selected patients, achieving a high clinical remission rate and significantly reducing the need for adjuvant treatment.
P0801 Real-world Effectiveness and Tolerability of Etrasimod in Active Ulcerative Colitis: A 26-week Observational Study
Authors: St-Pierre J , Choi D , Yanofsky R , Fear E , Rubin D T
Published: January 2025

Background

Etrasimod, a selective sphingosine-1-phosphate receptor modulator, has demonstrated efficacy in controlled trials for moderately to severely active ulcerative colitis (UC). However, real-world data on its effectiveness and tolerability have not been reported. This 26-week observational study evaluates clinical response and remission in UC.

Methods

Patient demographics, disease characteristics, prior therapies, and SCCAI scores were recorded at baseline and at weeks 2, 4, 8, 12, and 26. Clinical response (SCCAI reduction ≥3) and remission (SCCAI ≤2) were assessed, with statistical differences between time points determined by paired T-tests. Side effects and laboratory findings were collected at each time point.

Results

We treated 22 patients with etrasimod: median age 38.5 years (Q1-Q3: 33.5–45.8), median disease duration 5.5 years (Q1-Q3: 4–11.3). 82% of patients (n=18) had prior 5-ASA exposure, and 23% (n=5) had received advanced therapies. 82% of the patients (n=18) were started due to active inflammation confirmed by symptomatic, biochemical, or endoscopic findings, a subset (59%, n=13) had clinical symptoms (SCCAI ≥3) at etrasimod commencement. The mean SCCAI dropped from 3.4 at baseline to 2.0 at week 2 (p=0.04), 1.5 at week 4 (p=0.01), 1.3 at week 8 (p=0.05), 1.0 at week 12 (p=0.04) and 3.0 (p=0.07) among all patients (Figure 1A). At week 12, 64% had achieved clinical remission, however this dropped to 18% at week 26 in an intention-to-treat (ITT) analysis (Figure 1B). This was primarily driven by high rates of discontinuation during this period (10 patients by week 26). Similar trends were observed in the 13 patients with clinical symptoms at baseline (SCCAI≥3), where 62% achieved clinical remission at week 12 followed by a drop to 23% at week 26 (Figure 1C,D). As expected, the absolute lymphocyte count reduced over the initial weeks of treatment (Figure 1E); there were no infections reported. Only 1 patient received oral steroids at etrasimod start, and 3 received steroids by week 2; 3 of these 4 stopped etrasimod due to lack of efficacy. One patient remained on 5-ASA throughout, and 2 patients had 5-ASA added before week 12 due to symptom recurrence. Of the 5 patients with prior advanced therapies, none achieved remission at week 26. One patient reported transient light-headedness on etrasimod initiation, without arrhythmia.

Conclusion

We demonstrate the first real-world effectiveness of etrasimod in a tertiary population of UC, with the majority achieving remission within the first 12 weeks and about half maintaining it through week 26. Those who lost response were more often patients with prior advanced therapy treatment or those who needed steroids in the first 12 weeks. Etrasimod was safe and overall well-tolerated.
P0802 Effect of proctocolectomy with diverting ileostomy on Renal Function
Authors: Futatsuki R , Tani K , Kouroku M , Ito A , Yonezawa M , Ogawa S , Yamaguchi S
Published: January 2025

Background

Restorative proctocolectomy with ileal pouch anastomosis (IPAA) is the standard surgical procedure for ulcerative colitis, sometimes followed by diverting ileostomy. Renal function decline due to ileostomy has been reported, but there are few reports after IPAA with ileostomy. We investigated the changes in renal function and risk factors for its deterioration in patients after IPAA with ileostomy in this study.

Methods

Using the hospital medical record, we retrospectively reviewed patients with ulcerative colitis who underwent two stage IPAA (restorative proctocolectomy with ileal pouch anastomosis, either hand-sewn or stapled ileal pouch-anal anastomosis, diverting ileostomy at the first-stage and ileostomy closure in the second stage) between June 2003 and October 2020. The decline of renal function was defined as a decrease in estimated Glomerular Filtration Rate (eGFR) more than 30 ml/min/1.73m2 from the time of first-stage surgery to the time of ileostomy closure. The risk factors for renal function decline were examined in comparison with clinicopathological factors in two groups: patients with a decline in renal function (decline group) and patients without a decline in renal function (non-decline group).

Results

In total, 108 patients were included in the study. Eighteen patients (16.7%) were in the decline group and 90 patients (83.3%) were in the non-decline group. The eGFR of all patients decreased from 90.1 ml/min/1.73 m2 at the time of first-stage surgery to 84.3 ml/min/1.73 m2 at the time of ileostomy closure. The median time to ileostomy closure was 151 days (32-1221 days). In univariate analysis, the following factors were identified: severe (p=0.0154), laparoscopic (p=0.003), intraoperative blood loss (p=0.004), emergency surgery (p=0.009), and duration until ileostomy closure (p=0.008). In multivariate analysis, intraoperative blood loss of 192g or more (Odds ratio (OR): 3.724 (95% confidence interval (CI): 1.037-13.377, p=0.044)) and duration until ileostomy closure of 196 days or more (OR: 4.995 (95%CI: 1.451-17.201, p=0.011)) were identified as independent risk factors for worsening renal function.

Conclusion

eGFR decreased until ileostomy closure in patients with IPAA and diverting ileostomy. 16.7% of patients had a decrease in eGFR (eGFR) more than 30 ml/min/1.73m2. Factors associated with a decrease in eGFR were intraoperative blood loss more than 192g and duration until ileostomy closure more than 196 days.
P0803 Biosimilar Therapy in IBD: Real-World Evidence from Saudi Arabia
Authors: Mosli M H A , Bakkari S , Al Jahdali A , Batwa F , Hassanein A
Published: January 2025

Background

Inflammatory Bowel Disease (IBD) is a chronic condition with increasing incidence, particularly in newly industrialized countries. The high cost of biologic treatments has led to the development of biosimilars like infliximab CT-P13, which offer a more affordable alternative.

This study aims to evaluate the safety and effectiveness of a biosimilar (CT-P13) in Saudi Arabian patients with Crohn’s Disease (CD), fistulizing perianal CD, or ulcerative colitis (UC).

Methods

A non-interventional, observational cohort study was conducted in four medical centers in Saudi Arabia. The study included both naïve patients and those switched from the reference product. Patients received CT-P13 infusions over a period of 48 weeks. Safety was assessed by monitoring adverse events (AEs), and effectiveness was measured by clinical response and remission rates. Statistical significance was determined using p-values and confidence intervals.

Results

Participants: 156 patients (62 naïve, 94 switched). Adverse Events: 129 AEs reported in 57 patients; 95.3% were not related to treatment, 3.9% were treatment related. Effectiveness'Naïve CD Patients: Clinical response rates of 42.9% at week 14 (p < 0.05) and 30.8% at week 46 (p < 0.05); remission rates of 76.5% at week 14 (p < 0.01) and 70.6% at week 46 (p < 0.01). Naïve Fistulizing CD Patients: Clinical response rates of 27.3% at week 14 (p = 0.05) and 26.7% at week 46 (p = 0.05); remission rates of 13.6% at week 14 (p = 0.05) and 25.0% at week 46 (p < 0.05). Naïve UC Patients: Clinical response rates of 41.7% at week 14 (p < 0.05) and 42.9% at week 46 (p < 0.05); remission rates of 38.5% at week 14 (p < 0.05) and 50.0% at week 46 (p < 0.01). Switched Patients: Disease control rates of 100% in CD, 93.1% in fistulizing CD, and 93.3% in UC at week 48 (all p < 0.01).

Conclusion

Biosimilars are well tolerated and effective in achieving disease control, clinical response, and remission in Saudi Arabian patients with CD and UC. These findings support the use of CT-P13 as a cost-effective treatment option for IBD.

References

Najeeb H, Yasmin F, Surani S. Emerging role of biosimilars in the clinical care of inflammatory bowel disease patients. World J Clin Cases. 2022 May 16;10(14):4327-4333. doi: 10.12998/wjcc.v10.i14.4327. PMID: 35663066; PMCID: PMC9125297.
P0805 Sigmoidoscopy is sufficient as a surveillance tool in pediatric Ulcerative Colitis; full colonoscopy is not typically needed
Authors: Yuval Bar-Asher S , Lev-Tzion R , Orlanski-Meyer E , Ledder O , Shteyer E , Shamasneh I , Yogev D , Assa A , Baldassano R N , Griffiths A M , Turner D
Published: January 2025

Background

Sigmoidoscopy is a less invasive procedure than full colonoscopy, demands simpler preparation, requires shorter procedure time, and may be conducted with lighter sedation. Despite these advantages and the continuous nature of inflammation in ulcerative colitis (UC), which typically decreases from distal to proximal colon, the FDA recently requests full colonoscopy to assess UC in clinical trials (i.e. 3 colonoscopies in 54 weeks). Data to support this requirement are scarce in children. We, thus, aimed to assess the necessity of full colonoscopy versus limited sigmoidoscopy in pediatric UC.

Methods

We included two prospectively enrolled cohorts of children (0-18 years) with UC, both with identical data collection relevant to this study: one from a single-center prospective registry, and the other from a prospective validation of the TUMMY-UC, a patient-reported signs and symptoms for pediatric UC. In addition to explicit clinical, disease activity, labs and demographic data, the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) was recorded prospectively for each colonic segment. The first colonoscopy available after the time of diagnosis was included to better mirror the scenario of post-treatment follow-up monitoring, since the diagnostic procedure should always be full colonoscopy.

Results

A total of 85 patients were included (mean age 14 ± 3.4, 11 [13%] with endoscopic healing, 45 [53%] with mild colitis and 29 [34%] with moderate-severe colitis). The median UCEIS scores decreased progressively from the rectum and sigmoid (2, IQR:0-4) to the more proximal colon (descending 1, IQR:0-3; transverse and ascending 0, IQR:0-2; p < 0.001). Only 3 patients (3.5%) had inflammation in proximal segments without having inflammation in the rectosigmoid region. Another 10 patients (12%) had higher inflammation scores in the proximal colon than in the rectosigmoid (i.e. reverse gradient), though inflammation was still present in the rectosigmoid region.

Conclusion

In 96.5% of cases, endoscopic healing in the rectosigmoid region reflected endoscopic healing in the entire colon in children with UC. When inflammation was present in the rectosigmoid, in 86% the degree of colitis reflected the maximal endoscopic severity of the entire colon. These findings suggest that sigmoidoscopy may be a suitable routine post-treatment surveillance tool for pediatric UC patients and in the research setting in order to maximize feasibility and ethical considerations of clinical trials.
P0811 Comparative efficacy of vedolizumab and infliximab in patients with moderate-to-severe ulcerative colitis: a multicenter real world cohort study
Authors: Sun Y , Yang H
Published: January 2025

Background

Vedolizumab (VDZ) and infliximab (IFX) are both recognized as first-line treatment options for moderate to severe ulcerative colitis (UC). However, there is a paucity of comparative studies examining their real-world efficacy.

Methods

Patients with moderate to severe UC were consecutively enrolled from 11 centers. Efficacy were evaluated after 14 and 52 weeks. Logistic regression was conducted to identify independent risk factors for clinical remission.

Results

A total of 235 patients were enrolled, of which 154 received VDZ treatment and 81 received IFX treatment. 154 (65.5%) were male, with a median age of 40 (32, 49) years, a median disease duration of 7.0 (2.8, 11.9) years. The median baseline Mayo score was 9 (7, 11), and the median baseline partial Mayo score was 6 (4, 8). 16 patients (6.8%) had perianal lesions, and 41 patients (17.4%) had extraintestinal manifestations. At week 14, patients treated with IFX had higher clinical response rate (84.6% vs 66.2%, p = 0.003) but lower endoscopic remission rate (14.5% vs 34.3%, p = 0.003) compared to those treated with VDZ. There were no statistical difference in clinical remission rate between the two groups (39.7% vs 44.8%, p = 0.462). At week 52, there were no statistically difference in the modified Mayo score, partial Mayo score, clinical response rate, clinical remission rate, and endoscopic remission rate between IFX treatment group and VDZ treatment group (p>0.05). Multivariate regression analysis demonstrated that baseline disease extent was a predictor of clinical remission at week 14 of VDZ treatment (OR = 3.55, 95% CI 1.39–9.06, p = 0.008).

Conclusion

IFX group received higher clinical response rate but not endoscopic remission rate at week 14. The efficacy of IFX was comparable to VDZ at week 52. Disease extent was a predictor of clinical remission at 14 weeks with VDZ.
P0812 Establishing a target dysplasia detection rate (DDR) as a quality metric for Inflammatory Bowel Disease surveillance
Authors: Picardo S , Baker J , Geow R , Halpin S , Cheng W , Ragunath K
Published: January 2025

Background

Patients with inflammatory bowel disease (IBD) have an increased risk of developing dysplasia and colorectal cancer. Endoscopic surveillance is recommended, however, key quality performance metrics for surveillance are lacking. The aim of this study was to perform a systematic review and meta-analysis of the prevalence of dysplasia in patients undergoing IBD surveillance in the era of high-definition colonoscopy, in order to determine a target dysplasia detection rate (DDR) which can be used as a quality measure.

Methods

The trial protocol was registered with PROSPERO (CRD42024537521). An extensive search was performed of Medline, EMBASE, Web of Science and Cochrane Library databases to identify all prospective published studies (randomised controlled trials (RCT), observational cohort studies and crossover/tandem studies) of patients undergoing IBD dysplasia surveillance using high-definition colonoscopes. Several surveillance modalities were included (high-definition white light, dye spray chromoendoscopy, virtual chromoendoscopy, full spectrum endoscopy, autofluorescence and endomicroscopy with chromoendoscopy). Two reviewers independently evaluated studies for eligibility and methodological quality. All variables of interest were collected on a standardised form. A random-effects model was used to calculate an estimate of the pooled prevalence of dysplasia defined as the dysplasia detection rate. An estimate of the pooled prevalence of cancer was also determined. A sub-group analysis was performed, by surveillance modality, for all non-crossover/tandem studies where data was available.

Results

Twenty-five studies (11 RCT, 8 tandem/crossover studies and 6 observational cohort studies) were included, from a total of 3029 abstracts screened. For the calculation of dysplasia and cancer prevalence rates, a total of 4136 patients (55.2% male), mean age 49.4 years and mean disease duration 16.5 years met inclusion criteria. The pooled dysplasia detection rate was 16.5% (95% CI, 14% to 19%). (Figure 1). The pooled cancer detection rate was 0.1% (95% CI, 0 to 0.2%). Subgroup analysis by surveillance modality demonstrated similar pooled dysplasia detection rates with slight differences in mean procedural withdrawal times. (Table 1).

Conclusion

This is the first study that attempts to measure dysplasia detection rates in a systematic fashion in patients undergoing IBD surveillance colonoscopy in the high-definition colonoscopy era. The pooled dysplasia detection rate was 16.5% and cancer detection rate was 0.1%. We propose a conservative estimate dysplasia detection rate of 14% (the lower confidence limit in our study) as a target quality metric for IBD surveillance.
P0813 Integrated summary of safety of obefazimod for patients with moderately to severely active ulcerative colitis
Authors: Vermeire S , Peyrin-Biroulet L , Danese S , Dubinsky M , Dulai P S , Tilg H , Siegmund B , Hisamatsu T , Shan K , Jacobstein D , Cataldi F , Rabbat C , Sands B E
Published: January 2025

Background

Obefazimod is an oral, once-daily (QD), small molecule which enhances expression of microRNA-124 and is currently in phase 3 clinical trials for the treatment of patients with moderately to severely active ulcerative colitis (UC) [1]. Obefazimod demonstrated efficacy and safety in patients with UC across 4 clinical studies: two placebo-controlled Phase 2 induction trials, and two subsequent open-label maintenance (OLM) studies [2, 3]. Here we report an integrated safety analysis of those studies in the UC clinical program.

Methods

Exposure-adjusted incidence rates (EAIRs per patients-years [PY]) of treatment emergent adverse events (TEAEs) were examined among patients from the induction trials (NCT03093259, NCT03760003), and the OLM studies (NCT03368118, NCT04023396). Patients received one of three obefazimod doses (25mg, 50mg or 100mg QD) or placebo during induction, and all patients received 50 mg QD during OLM studies.

Results

Demographics and disease characteristics were similar among treatment groups. Exposure for all obefazimod-treated patients (N=274) was 440.1 PY including induction and maintenance periods. EAIR of TEAEs per PY was 1.40 in obefazimod-treated patients and 2.40 in placebo-treated patients (N=73), with TEAEs occurring in 78.5% and 47.9% of patients, respectively (Table 1). The most common TEAEs (EAIR per PY ≥ 0.05) in all obefazimod-treated patients included headache, Covid-19, ulcerative colitis, nasopharyngitis, and nausea. For each of these TEAEs, the incidence per PY was numerically lower in the group of all obefazimod-treated patients relative to placebo.

Conclusion

This integrated safety analysis of the 4 completed studies in the obefazimod UC clinical program indicates that exposure-adjusted incidence rates of TEAEs were generally numerically lower among patients treated with obefazimod relative to placebo. Integrated safety data further support a favorable safety and tolerability profile.

References

1. Vermeire S, et al. J Crohns Colitis. 2023; 17: 1689-1697

2. Vermeire S, et al. Gastroenterology 2021; 160: 2595-2598

3. Vermeire S, et al. The Lancet Gastroenterology & Hepatology. 2022; 7: 1024-1035.
P0814 Transmural healing in Crohn’s disease: Real-world insights from the SUNRISE study on vedolizumab using intestinal ultrasonography
Authors: Carter D , Fiorino G , Biedermann P , Cassanelli F , Meyer M , Novak K L , Kopylov U
Published: January 2025

Background

The use of patient-centric monitoring modalities for assessing therapies, such as vedolizumab (VDZ), are of growing interest to optimize disease outcomes in patients (pts) with Crohn’s disease (CD). Transmural healing is an emerging outcome assessed by intestinal ultrasonography (IUS), which allows frequent evaluation of CD.1,2 Real-world evidence on the effectiveness of current treatments to induce and maintain transmural response to inform treatment decisions is limited. The SUNRISE study aims to describe pts with CD treated with VDZ achieving a composite outcome of complete remission, and transmural response, utilizing IUS.

Methods

SUNRISE is an ongoing observational, prospective study (NCT05192863) being conducted across 10 sites in Canada, Israel and Italy. Adults with moderately to severely active CD, with a bowel wall thickness of >3 mm based on IUS, and who newly initiated intravenous VDZ are eligible. Complete remission (defined as a composite endpoint of clinically corticosteroid-free [Harvey–Bradshaw Index score of <5 points and no concomitant corticosteroids], biochemical [C-reactive protein and faecal calprotectin normalization] and transmural remission [assessed by IUS]), and transmural response after VDZ treatment are reported after induction with VDZ (Weeks 10/14) and every 6 months until Month 18 or early discontinuation. Methodological details are shown in the Figure.

Results

This interim analysis included 70 pts; median (interquartile range [IQR]) age was 50.0 (39.0–67.0) years, time since CD diagnosis was 4.0 (0.9–17.2) years and treatment duration (n=69) was 5.0 (3.2–6.1) months. At Month 6, the proportion of pts achieving complete remission, and transmural remission and response were 3/11 (27.3%), 9/28 (32.1%) and 12/28 (42.9%) pts, respectively; data at Weeks 10/14 are shown in the Table. Median (IQR) Short Inflammatory Bowel Disease Questionnaire total score was 4.3 (3.7–5.6) at baseline, 4.5 (3.4–5.3) at Week 10, 4.7 (3.9–5.6) at Week 14 and 5.0 (4.4–6.1) at Month 6. At Month 6, 10/21 pts (47.6%) ranked IUS as their preferred test over colonoscopy, magnetic resonance elastography and computed tomography enterography. Of 40 pts with available data at Month 6, 6 (15.0%) discontinued treatment, 5 (12.5%) switched to subcutaneous VDZ and 1 (2.5%) skipped ≥1 dose of VDZ. During the observation period, 2/70 pts (2.9%) had a CD-related hospitalization, and 1/70 pt (1.4%) each had a CD-related emergency room visit or CD-related surgery (fistula removal).

Conclusion

The SUNRISE study provides real-world evidence for the use of VDZ to achieve transmural healing in pts with CD and supports pt preference for IUS over other monitoring modalities. Additional follow-up data are required to confirm these findings.

References

1.Ilvemark J.F.K.F. et al. J Crohns Colitis 2022;16:554–80.

2.Turner D. et al. Gastroenterol 2021;160:1570–83.
P0815 Oral alpha 4 beta 7 (α4β7) integrin antagonist EA1080 (NSHO-101) demonstrates target engagement and α4β7 integrin receptor occupancy following once-daily administration in healthy volunteers
Authors: Feagan B G , Yazawa Y , Seki T , Watanabe E , Ohishi H , Ueo H , Saito C , Lorch U
Published: January 2025

Background

EA1080 (NSHO-101) is a selective, oral small molecule α4β7 integrin antagonist being advanced for the treatment of inflammatory bowel disease (IBD). EA1080 (NSHO-101) was safe and well tolerated and resulted in near complete inhibition of MAdCAM-1 binding to α4β7 integrin (receptor occupancy) on peripheral blood CD4+ T cells following twice-daily dosing with Formulation X in a healthy volunteer phase 1 study (DDW 2024: Su1789; NCT04223960). No effect on peripheral blood lymphocyte count was observed, confirming no specific engagement of α4β1 integrin. Here pharmacokinetics (PK) and pharmacodynamics (PD) results from a once-daily formulation are presented.

Methods

The PK and PD results from multiple ascending dose (MAD) cohorts with a formulation utilizing once-daily dosing were assessed in a healthy volunteer phase 1 study. Peripheral blood lymphocyte counts were assessed across the dosing period.

Results

Once-daily administration of EA1080 (NSHO-101) resulted in sustained, near-complete inhibition of MAdCAM-1 binding to α4β7 integrin on peripheral blood CD4+ T cells (≥95% receptor occupancy) across the dosing interval (24 hours). This correlated with plasma concentrations of active metabolite of EA1080 (EA1080-M) and approximated the level of receptor occupancy seen with twice-daily dosing with Formulation X. Plasma concentrations of EA1080-M reached steady-state levels within 3-4 days, and this correlated with maximal inhibition of MAdCAM-1 binding (receptor occupancy). No consistent trend in peripheral blood lymphocyte counts was observed across the dosing period.

Conclusion

These results demonstrate that once-daily oral administration of EA1080 (NSHO-101) results in near complete inhibition MAdCAM-1 binding to α4β7 integrin (≥95% receptor occupancy) across the dosing interval. No effect on peripheral blood lymphocyte counts was observed, confirming no specific engagement of α4β1. These results support continued development of a once-daily dosing formulation for future clinical studies.
P0816 Dietary habits of ulcerative colitis patients under follow-up in a Pediatric Inflammatory Bowel Disease Unit
Authors: Herrador Lopez M , Martín-Masot R , Sarbagilli C , Navas-López V M
Published: January 2025

Background

A Western dietary pattern characteristics was suggested to have a role in the pathogenesis of ulcerative colitis (UC). Poor dietary pattern can exacerbate the patients’ symptoms and lead to significant nutrient deficiencies. However, data regarding dietary habits and nutritional needs are scarce. Our study aimed to prospectively evaluate dietary intake and habits in peadiatric patients with UC at a Spanish tertiary hospital.

Methods

In this prospective observational study, peadiatric UC patients were followed up, during which their dietary habits were collected. Patients were asked to complete the KIDMED questionnaire for adherence to the Mediterranean diet (MD) and a 3-day food diary. The degree of food processing was assessed using the NOVA classification system, which classifies all food products into four main groups.

Results

A total of 47 patients were included, with a mean age of 11.9±3.3 years (57% female), and a median follow-up of 2.8±5.4 years. The mean caloric intake was 1919.07 ± 292.8 kcal, and 55.31% of patients did not cover their energy requeriments. Protein and saturated fat intake exceeded the recommended daily intake (RDI): mean protein intake was 2.13±0.8g/kg (239.06% of RDI), and saturated fatty acids was 31.65±7.9% of total fat. In contrast, fiber, calcium and iron intake were below recommendations: mean fiber was 13.44±2.9g (75.1±24.7% of RDI), calcium was 457.7±239.3mg (41.6±26.2% of RDI) and iron 8.3±3.4mg (75.3±37.2% of RDI). The average KIDMED score was 6.2 points, with only 15 patients (31.9%) presenting high adherence to the MD. Of the remaining patients, 26 (55.3%) needed to improve their diet quality, and 6 (12.7%) had very low diet quality. Regarding the NOVA classification, 7 patients (14.9%) consumed more than 40% of their total energy from ultra-processed foods (NOVA 4), while 23 (48.9%) had less than 40% of their energy intake coming from unprocessed or minimally processed foods (NOVA 1).

Conclusion

Our results highlight that a substantial proportion of pediatric UC patients have suboptimal dietary patterns, characterized by high intake of UPF and saturated fats, alongside low intake of fiber, calcium, and iron. These findings suggest a need for tailored follow-up with a specialized dietitian within the multidisciplinary care team. Further research is essential to clarify the impact of diet on UC.
P0820 Video-assisted anal fistula treatment (VAAFT) in Crohn´s perianal disease: a Brazilian single-center prospective cohort study
Authors: Gardere Camergo M , Vital Pinheiro Saito L , Natali Moraes P , Minatel Vidal de Negreiros L , Nunes Angelo S , Real Martinez C A , Oliveira Magro D , Saddy Rodrigues Coy C
Published: January 2025

Background

Perianal involvement is identified in one-third of patients with Crohn’s disease, including fistulas, fissures and skin tags. Perianal Crohn´s disease (PCD) is associated with decreased quality of life, due to significant physical and psychologic symptoms. Video-assisted anal fistula treatment [VAAFT] is a minimally invasive surgical technique for anal fistulas, accessing primary and secondary fistula tracks for drainage and fulguration of inflammatory tissue. Our study reports the use of VAAFT for management of PCD fistulas along with medical therapy, aiming to improve symptoms and promote healing.

Methods

A single-center prospective study was conducted in consecutive patients with symptomatic PCD fistulas submitted to VAAFT, from January 2020 to January 2024. The surgical procedure involved an perianal exam under analgesia and VAAFT for fistuloscopy and cauterization of fistula tracks, with setons installation and\or replacement in order to maintain postoperative drainage. The primary endpoint was completion of the ‘Perianal Disease Activity Index (PDAI)’ questionnaire at 8 weeks postoperatively. Secondary outcome measure was ´IBDQol´ questionnaire at 8 weeks postoperatively, postoperative complications and the 30-day re-operation rate.

Results

Thirty-nine patients underwent VAAFT procedure for PCD during the study period. In total, 34/39 patients [87%] provided PDAI data, demonstrating a statistically significant improvement in scores of discharge, pain and sexual activity scores. In total, 34/39 patients [87%] provided IBDQol data, demonstrating a statistically significant improvement. The only complication was sepsis in one female 28-year old patient at the immediate postoperative period, successfully managed with clinical treatment in intensive care unit. There was no re-operation in 30-day period.

Conclusion

Our study demonstrates the feasibility, safety and importantly an improvement in patient-reported outcomes of patients undergoing VAAFT for management of PCD fistulas. VAAFT reduced the symptoms of discharge and paiin patients with complex refractory PCD fistulas.