bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0994 Effectiveness of Risankizumab in an Emirati Crohn’s Disease Cohort: Real-World Insights on Induction, Maintenance, and Dose Intensification Outcomes
Authors: Alzaabi M N , Swaid T K , Ahmed H A , Alahmed M A , Omar N M , Kumar K K C , Ahmed E F , Malik T A , Quraishi M N 
Published: January 2025

Abstract

Background
Risankizumab, an IL-23 inhibitor, has shown efficacy in RCTs and real-world studies for inducing and maintaining clinical remission in Crohn’s disease (CD) patients. We report the largest real-world evidence from the Middle East evaluating risankizumab’s effectiveness and safety in advanced therapy (AT) naive and exposed patients along with outcomes following dose intensification.

Methods
A prospective observational study in an Emirati cohort at tertiary IBD center in UAE evaluated clinical outcomes at induction (3-5 months) and maintenance (12-14 months), assessing clinical remission (CDAI &lt;150), clinical response (CDAI improvement by 100 points) and endoscopic response (≥50% SES-CD improvement). Long-term outcomes following dose intensification were recorded for patients with inadequate or loss of response after 12 months. Continuous variables were reported using descriptive statistics, and predictors of clinical remission were identified using logistic regression.

Results
A total of 37 patients treated with risankizumab were included in the analysis of which 35.1% were AT naive, and 64.9% had prior AT exposure. The median age was 33 years (IQR 26-42) and the median follow-up was 7.5 months (IQR 4.5-16.5). AT-naive patients initiated risankizumab at a median of 31 days from diagnosis (IQR 31-61). Post-induction clinical remission was achieved in 43.2% (16/37), with higher remission observed in AT-naive patients (53.8%) compared to AT-exposed patients (37.5%). Clinical response during induction was observed in 89.2% of the total cohort, with 92.3% response in the AT-naive group and 87.5% in the AT-exposed group. Of the patients with a follow up period of &gt;12 months, clinical remission and response was achieved in 60% (9/15) and 93.3% (14/15) of the total cohort respectively. Endoscopic response was achieved in 81.8% (9/11) of patients undergoing colonoscopy between 8 and 12 months. Prior AT exposure significantly reduced the odds of achieving clinical remission (p&lt;0.05). Age, perianal disease, baseline Hb, albumin, CRP, CDAI, SES-CD, and prior ustekinumab exposure did not affect odds of remission. Response was re-captured in 4/6 patients with secondary loss of response following 4-weekly dose intensification. No adverse events were observed during the follow-up period.

Conclusion
Risankizumab was highly effective for Crohn’s disease in an Emirati cohort, especially in AT-naive patients with a short time from diagnosis to treatment. High endoscopic response was noted, and dose intensification frequently restored response in patients with a secondary loss. Prior advanced therapy exposure correlated with lower remission rates, highlighting the importance of early targeted intervention.
P0995 Use of biologics before ileal pouch-anal anastomosis is not associated with inflammatory pouch disease
Authors: Yan Y , Wang F , We J , Gong J 
Published: January 2025

Abstract

Background
Inflammatory pouch disease (IPD) is a common complication after ileal pouch-anal anastomosis (IPAA) surgery. The risk factors contributing to the onset of IPD, particularly the role of preoperative biological treatment, remain unclear. The purpose of this study was to investigate the effects of biologic use on the occurrence of post-IPAA complications and the risk factors for IPD.

Methods
These was a retrospective cohort analysis of patients who underwent IPAA at Jinling hospital between November 2003 and September 2023. The patients were divided into two groups according to the presence or absence of exposure to biologics. The primary outcome was the occurrence of postoperative IPD. The postoperative complications were compared between groups, and logistic regression was used to identify IPD risk factors.

Results
Among the 175 patients, 47.43% had received biologics before surgery, and 38.9% developed IPD. No significant difference was observed in the incidence of postoperative IPD between groups (p = 0.484). Logistic regression revealed that biologic use was not a risk factor for IPD (OR = 0.8, 95% CI: 0.44–1.48, p = 0.485), whereas ulcerative colitis diagnosis at &gt;35 years of age was a protective factor against IPD (OR = 0.47, 95% CI: 0.24–0.93, p = 0.029), and C-reactive protein &gt;45 mg/L was a risk factor for IPD (OR = 2.37, 95% CI: 1.12–5.02, p = 0.025).

Conclusion
The use of biologics before IPAA was not associated with IPD, but might be associated with a high preoperative CRP level and younger age at UC diagnosis.
P0998 Mucosal Healing and Long-Term Medication Survival in Crohn’s Disease Patients Treated with Anti-TNF Therapy
Authors: Lopes M , de Queiroz Prado Bittencourt N , Furieri Rigo F , Souza de Oliveira E C , Soares Prates Herrerias G , Pinheiro Baima J , Yukie Sassaki L 
Published: January 2025

Abstract

Background
Mucosal healing (MH) has emerged as a pivotal therapeutic goal in the management of Crohn’s disease (CD), serving as a key prognostic marker associated with sustained clinical remission, reduced hospitalization rates, and fewer surgical interventions. Anti-TNF therapy, encompassing infliximab (IFX) and adalimumab (ADA), has significantly advanced the treatment landscape by promoting endoscopic healing. This study aimed to evaluate the long-term survival of anti-TNF therapy and to compare clinical and endoscopic remission rates between IFX and ADA in CD patients.

Methods
CD patients treated with anti-TNF therapy were included. The Crohn’s Disease Activity Index (CDAI) was used to assess the clinical activity of the disease. Endoscopic activity was assessed using the Simplified Endoscopic Score for Crohn’s Disease (SES-CD). The variables were clinical response (drop in CDAI &gt; 70 points) and clinical remission (CDAI &lt; 150 points), and endoscopic response (drop in SES-CD of at least 50% in relation to the initial score), and endoscopic remission (SES-CD ≤ 2 points).

Results
92 patients were included, mean age 40.49±13.67 years, 48 (52.2%) using ADA and 44 (47.8%) using IFX. Clinical/endoscopic remission rates were 77.08%/59.09% in 1 year, 74.29%/68.57% at 2 years, 81.25%/77.42% at 3 years, and 88%/72% in 5 years. Medication survival rates for clinical remission were 82.95% at 1 year, 74.67% at 3 years, 56.89% at 5 years, and 23.01% at 10 years. The average survival was 7.46 years, with no difference between ADA and IFX (Log Rank=0.36). Survival rates for endoscopic remission were 67.72% at 1 year, 59.74% at 3 years, 45.46% at 5 years, and 12.90% at 10 years. The average medication survival was 5.61 years, with higher rates in the IFX group (Log-Rank=0.0043). Clinical and endoscopic response rates were 81.25%/73.86% at 1 year, 74.29%/80% at 2 years, 84.38%/80.65% at 3 years, and 92%/80 % in 5 years.

Conclusion
Anti-TNF therapy demonstrated a 50% survival rate at 5 years, with IFX showing superior long-term medication survival in achieving endoscopic remission. These findings reinforce the importance of mucosal healing as a critical therapeutic endpoint in CD management and highlight the durability of anti-TNF agents in clinical practice

Figure 1: Survival curves for clinical (A; Log-Rank = 0.3653) and endoscopic (B; Log-Rank = 0.0043) remission comparing adalimumab (ADA) versus infliximab (IFX).
P0999 Efficacy and safety of different biologics in first line therapy in Crohn’s disease: a multicentric retrospective comparative analysis
Authors: Preda C M , Podgoreanu B , Trifan A , Tantau A , Negreanu L , Tieranu C , Bucurica S , Minea H , Buzuleac M , Popescu R , Bota A , Istratescu D , Stroie T , Tugui L , Diculescu M 
Published: January 2025

Abstract

Background
Biological therapy is the most important pathogenic treatment in moderate to severe Crohn’s disease (CD), but there are few studies in the literature that compare the effectiveness and safety of several biological drugs. The aim of this study is to compare efficacy and safety of different biologics as first line therapy in CD.

Methods
326 patients from 6 Gastroenterology departments from Bucharest, Iasi and Cluj treated between 2006 and 2024 were included in the study. 47 were excluded because they received only Mesalazine. 279 were included in the final analysis. The main outcomes were: clinical response at 12 weeks of treatment (complete response = clinical remission, partial response= decrease of CDAI ≥ 25% of the initial value without remission or primary non-response) and serious adverse events leading to therapy discontinuation.

Results
The main characteristics of the studied patients are shown in the table 1. Median therapy duration was 48 months (3÷330). 47% of patients received Adalimumab, 42% were treated with Infliximab, and in 9% Ustekinumab was given. The flowchart of the study is presented in the Figure 1. The complete response rate was similar for the 3 biologics studied: 70%, the non-response rate was also similar: 8%, but persistence on therapy at 2 years was better for Ustekinumab (62%) and Adalimumab (40% ), compared to Infliximab (34%) (p=0.03). Serious adverse events leading to therapy discontinuation were more frequent in those treated with Infliximab (10%) compared to Adalimumab (3%) and Ustekinumab (6%) (p=NS). Because only 25 individuals received Ustekinumab in first line, predictive factors for complete clinical response were searched only for Infliximab and Adalimumab. Good predictive factors of response to Infliximab were: absence of perianal disease (p=0.003), low value of CDAI at initiation (p&lt;0.001), increased hemoglobin level (p=0.01), lack of stricturing behavior (p=0.02), short interval from diagnosis to start of therapy (p=0.04). Several prognostic factors for a good response to Adalimumab were identified: absence of perianal disease (p=0.03), low CRP at initiation (p=0.006), non-stricturing behavior (p=0.02), short interval between symptom onset and therapy initiation (p=0.001).

Conclusion
All three biological agents used in real life for Crohns’ disease therapy show similar efficacy, with a complete response rate of aprox.70% and a nonresponse rate of 8%, but persistence on therapy at 2 years was significantly better for Ustekinumab (62%) and Adalimumab (40% ), compared to Infliximab (34%). Serious adverse events leading to therapy discontinuation were more frequent in patients treated with Infliximab (10%) compared to those who received Ustekinumab (6%) or Adalimumab (3%).
P1001 Efficacy and safety of an oral tyrosine kinase 2 inhibitor VTX958 in moderately to severely active Crohn’s disease: a randomised, double-blind, placebo-controlled, phase 2 trial
Authors: Danese S , Jairath V , Sands B E , Schreiber S , Panaccione R , D’Haens G , Lindstrom B , Liu K , Sandborn W , Rubin D T , Peyrin-Biroulet L , Vermeire S , Naik S 
Published: January 2025

Abstract

Background
Tyrosine kinase 2 inhibitors (TYK2i) are a novel class of therapies for immune-mediated inflammatory disorders, including Crohn’s disease (CD). A phase 2, multicentre, randomised, double-blind, placebo-controlled trial assessed the efficacy and safety of the oral selective TYK2i VTX958 in CD.

Methods
Adults (N=109) with moderately-to-severely active CD (CD Activity Index [CDAI] 220-450; Simple Endoscopic Score for CD [SES-CD] ≥6 [≥4 for isolated ileal CD]) and inadequate/loss of response or intolerance to conventional or biologic therapies were randomised 1:1:1 to 12-weeks twice daily treatment with placebo or VTX958 (225mg or 300mg). The primary endpoint was CDAI change from baseline at week 12. Additional secondary endpoints are described in the Table. Changes from baseline in C-reactive protein (CRP) and faecal calprotectin (FCP) concentrations at week 12 were exploratory endpoints.

Results
Mean CDAI change from baseline at week 12 was -113.6, -134.1, and -104.3 for VTX958 300mg, 225mg, and placebo, respectively (p&gt;0.05; see Table). Conversely, significantly greater SES-CD reductions from baseline at week 12 were observed for VTX958 300mg (-2.7) and 225mg (-3.5) compared to placebo (2.1; p=0.0005 and p&lt;0.0001, respectively), and significantly greater proportions of patients achieved endoscopic response with VTX958 300mg (32.4%) and 225mg (24.3%) treatment compared to placebo (5.7%; p=0.007 and p=0.026, respectively). Although secondary clinical endpoints alone were not significantly different between VTX958 and placebo (Table), combined endoscopic response and clinical remission and clinical-biomarker response rates were significantly higher for VTX958 300mg compared to placebo (18.9% vs 2.9%, p=0.041, and 43.2% vs 14.3%, p=0.011, respectively). Greater reductions in CRP and FCP concentrations compared to placebo were observed with both VTX958 doses. Most adverse events (AE) were mild-to-moderate and comparable across treatment groups. No serious infections, thromboembolic, major adverse cardiovascular events, or deaths occurred in the VTX958 groups. Overall rates of skin reactions were also similar between treatment groups. Rash and acne occurred at a higher rate in the VTX958 groups compared to placebo, most of which were mild, except for one moderate AE of acne in the VTX958 225mg group.

Conclusion
Twelve weeks treatment with VTX958 was well-tolerated in patients with CD. Although the primary endpoint of CDAI change from baseline was not met, higher rates for most objective outcomes were observed with VTX958 300mg, including endoscopic response and combined clinical remission and endoscopic response. Additional data are needed to determine the long-term safety and efficacy of VTX958 in CD.
P1013 Adverse Events of Methotrexate in Paediatric Inflammatory Bowel Disease: A Retrospective Cohort Study
Authors: Vermeer E , Soetens E L , Struys E A , de Boer N K H , de Jonge R , de Meij T G J 
Published: January 2025

Abstract

Background
Methotrexate (MTX) is frequently prescribed in paediatric inflammatory bowel disease (IBD), with laboratory monitoring routinely performed to detect adverse events (AEs) such as hepatotoxicity and myelotoxicity. However, data on the incidence of these AEs in paediatric IBD remain limited. This study aims to assess the incidence of MTX-induced AEs in paediatric IBD, and to identify factors associated with AEs.

Methods
We conducted a retrospective monocentre cohort study, including all paediatric IBD patients initiating MTX at the Amsterdam UMC between 2010 and 2023. We collected demographic data, disease characteristics, and laboratory results. We specifically evaluated the occurrence of hepatotoxicity, myelotoxicity, and gastrointestinal (GI) side effects (nausea and vomiting). The severity of AEs was assessed according to the Common Terminology Criteria for Adverse Events. Shortly, grade 1 hepatotoxicity was defined as upper limit of normal (ULN)-2.5 times ULN, grade 2 as 2.5-5 times ULN, and grade 3 as 5-20 times ULN. Myelotoxicity was defined as leukopenia, neutropenia and/or thrombocytopenia. Incidence rates were calculated, and regression analyses were performed to assess potential predictors of MTX-induced AEs.

Results
A total of 208 paediatric IBD patients (179 CD, 18 UC, 10 IBD-U) starting MTX therapy were identified, 111 of whom used MTX as immunomodulator alongside a biological. Mean dose at initiation was 13 mg/week (±3.21SD), and 66.5% received MTX orally, versus 33.5% subcutaneous administration. All used folic acid. Hepatotoxicity was observed in 85 patients (40.1%), of which the majority (n=52, 63.4%) classified as grade 1, while 10 patients (12.2%) showed grade 3 toxicity. Myelotoxicity occurred in 43 cases (20.7%), most of which presented as mild toxicity (n=35, 83.3%), with no cases of severe toxicity. GI side effects were reported in 95 patients (45.7%). MTX was permanently discontinued in 24 patients (11.5%) due to hepatotoxicity, in 2 patients (1.0%) due to myelotoxicity, and in 35 patients (16.8%) due to GI side effects. The incidence density of AEs was 0.25 per person-year, with a total of 480 events across 1908 person-years. Female sex (RR 1.4, 95% CI [1.12–1.78], p=0.004) and MTX dose (RR 0.9, 95% CI [0.89– 0.97], p=0.002) were significant predictors of hepato- and/or myelotoxicity. Female sex (RR 1.5, 95% CI [1.17–1.97], p=0.002) and subcutaneous administration of MTX (RR 0.5, 95% CI [0.41–0.73], p&lt;0.01) were significant predictors of GI AEs.

Conclusion
Our findings indicate that severe MTX-induced AEs in paediatric IBD are uncommon, and that MTX-related AEs rarely necessitate therapy cessation. Female sex, MTX dosage, and subcutaneous administration were significant predictors of MTX-induced AEs.
P1023 Clinical study of composite sophora colon-soluble capsules combined with vedolizumab in the treatment of Ulcerative Colitis
Authors: Li X , Xie Y , Tian F 
Published: January 2025

Abstract

Background
There are limited data on the treatment of ulcerative colitis(UC) with in combination with Chinese herbs.The aim of our study was to determine the effectivenes and safety of Vedolizumab combined with Composite Sophora Colon-soluble Capsules(CSCC) use in ulcerative colitis.

Methods
We identified patients with ulcerative colitis who received CSCC and(or) Vedolizumab between 2021 and 2024 and divided them into the Vedolizumab + CSCC and the Vedolizumab group.The primary end-point was efficacy, based on improvements in inflammatory markers, clinical and endoscopic response.The secondary end-point was safety.

Results
Of the 31 patients receiving combination therapy there were significantly more patients had a 14-week clinical response and clinical remission compared with patients receiving Vedolizumab alone (74% vs 43%,P=0.036;21% vs 0, P=0.045) ;Significantly more patients responded clinically and endoscopically at 54 weeks (95% vs 68%, P=0.026;76% vs 42%, P=0.028).The difference of C-reactive protein decreased significantly at week 0 compared with week 2, 6, 14 and 54 after treatment (all P &lt;0.05).There were no serious adverse events or deaths.

Conclusion
Vedolizumab combined with CSCC appears to be an effective option for the patients with UC that is inadequately controlled by Vedolizumab alone.Large prospective studies are needed to confirm these findings.
P1028 Personalised co-culture model of intestinal organoids and immune cells for evaluating biological therapy response in ulcerative colitis patients
Authors: Tilinde D , Inciuraite R , Kulokiene U , Kiudelis V , Jonaitis L V , Kupcinskas J , Skieceviciene J 
Published: January 2025

Abstract

Background
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) affecting approximately 5 million people worldwide and is characterised by mucosal inflammation that may spread throughout the colon1. Existing therapies often have limited effectiveness or cause severe side effects2. Due to the absence of standardised criteria for selecting the most effective treatment for IBD, innovative preclinical drug testing systems are urgently needed.

Methods
The effect of upadacitinib (UPA) was tested in personalized co-cultures of colonic epithelial cells and macrophages derived from UC patients (n=12) and control (Con) individuals (n=11). Inflammation was induced with inflammatory cytokines TNF-α (10 ng/mL) and IFN-γ (10 ng/mL). Barrier integrity was measured by transepithelial electrical resistance (TEER). Expression of TNF-α, CCL5, and CXCL9 genes was evaluated using qRT-PCR. Data comparison was conducted using the Wilcoxon rank-sum test. A difference between the values was considered significant when p ≤ 0.05 or padj. ≤ 0.05.

Results
In cell cultures stimulated with inflammatory cytokines, barrier permeability increased (TEER decreased – Con: by 452.03 Ω·cm2, UC: 39.3 Ω·cm2), which partially recovered after removal of inflammatory factors (TEER increased – Con: by 65.91 Ω·cm2, UC – only 47.31 Ω·cm2). Epithelial integrity was restored after incubation with UPA (TEER increased – Con: by 116.82 Ω·cm2; UC: by 226.64 Ω·cm2). At the molecular level, overnight stimulation with TNF-α and IFN-γ increased expression of CXCL9 gene in epithelial cells (UC: fold change (FC) = 3064.49 padj. = 2.07 x 10-5; Con: FC = 664.44, padj. = 2.00 x 10-2) and macrophages (UC: FC = 140.47 padj. = 0.01; Con: FC = 314.43, padj. = 0.01) in both groups. Co-culture treatment with UPA showed an important trend of patient-specific response to therapeutic agent, which probably was the most important factor of non-significant values for observed changes in CCL5, CXCL9, TNF-α expression analysing summarized data.

Conclusion
To conclude, treatment with TNF-α and IFN-γ reduced epithelial barrier integrity and increased the expression of the inflammatory gene CXCL9 in both epithelial cells and macrophages. UPA tended to restore this disrupted barrier integrity. However, the effects of UPA on gene expression in both cell types showed variable impacts and effectiveness, revealing an individualized response to this biological agent.

References
1.Le Berre, C., et al. (2023). Ulcerative colitis. The Lancet. 402(10401):571-584. doi:10.1016/S0140-6736(23)00966-2
2.Singh, S., et al. (2020). AGA technical review on the management of moderate to severe ulcerative colitis. Gastroenterology. 158(5):1465-1496.e17. doi:10.1053/j.gastro.2020.01.007.
P1036 The PODIUM Study: A three-arm comparison of target therapies after anti-TNFα in ulcerative colitis – an interim analysis
Authors: Privitera G , Bezzio C , Savarino E , Pugliese D , Noviello D , Rodriguez-Lago I , Barreiro de Acosta M , Onali S , Fantini M , Kopylov U , Karmiris K , Yanai H , Gutierrez-Casbas A , Pastorelli L , Chaparro M , Zabana Y , Armuzzi A 
Published: January 2025

Abstract

Background
Anti-tumor necrosis factor(TNF)α are the first target therapies approved to treat ulcerative colitis(UC). Drugs with different mechanisms of action(MoA) have then entered the market, but data on the optimal management of UC after failure of 1-line anti-TNFα are lacking.

Methods
The PODIUM study is a retrospective, observational study comparing the real-life effectiveness and safety of 2-line vedolizumab(VDZ), ustekinumab (UST) and JAK inhibitors(JAKi). Consecutive UC patients(pts) failure to 1+ anti-TNFα and never exposed to other MoA were enrolled from 13 European centres. Sociodemographic data, data on clinical activity and adverse events of interest(AEIs) were collected, from the initiation of 2-line therapy until 1 year of observation/drug discontinuation/last follow-up. The primary outcome was steroid-free clinical remission(SFCR); inverse probability of treatment weighting(IPTW) was applied to all outcomes. This interim analysis includes data collected up to August 2024; data collection is still ongoing.

Results
Data on 352 patients (187VDZ, 76UST, 89JAKi) were included. Baseline characteristics are presented in Table1. After IPTW, the cumulative probability of achieving SFCR during the first year was 52%, 68% and 71% for VDZ, UST and JAKi, respectively; both UST and JAKi were superior to VDZ at Log-rank test(p&lt;0.05), with no differences between the two (Figure1). Stool frequency scores were significantly lower at 12 months in the UST- and JAKi-groups, compared to the VDZ-group(0.5 and 0.5 vs 1.2, p&lt;0.05 for both); rectal bleeding scores were nearly significantly lower at 12 months in the UST- and JAKi-groups, compared to the VDZ-group(0.2 and 0.2 vs 0.6, p&lt;0.05 for both). Recorded AEIs were 10(5.3% of VDZ pts, 4 infections) in the VDZ group, 7(9.2% of UST pts, 1 infection) in the UST group, 17(19.1% of JAKi pts, 10 infections including 1 Zoster reactivation) in the JAKi group.

Conclusion
This preliminary analysis suggests that both UST and JAKi might have superior effectiveness, compared to VDZ, as second-line agents in patients with UC, after anti-TNF-α. A significantly higher rate of AEIs was observed in the TOF group. Confirmatory analysis with a larger sample size will be performed.