bluuebunny/crossref_metadata_2025 huggingface dataset:
P0986 Sequencing of biological therapies and impact on persistence: Report from a tertiary referral center
Authors: Amato L M , Antoci C , Melatti P , Di Giorgio F , Salerno I A , Ajovalasit R , Di Prima L , Bracciamà E , Scalia S , Celsa C , Cappello M ,   University of Palermo
Published: January 2025

Background

Biologics and small molecules are increasingly used in inflammatory bowel diseases (IBD). However, real-world data on sequence choices are still limited as well as the impact of treatment sequence on outcomes. The aim of this study was to evaluate the treatment persistence for different lines of biological drugs in two samples of patients, one suffering from Crohn’s disease (CD) and the other from ulcerative colitis (UC), refractory to conventional therapy.

Methods

This retrospective-prospective real world study included consecutive IBD patients followed in our IBD tertiary referral center. Sankey diagrams were used to describe sequencies. Treatment persistence was assessed using Kaplan-Meier curves and Hazard Ratios (HR) were calculated to compare persistence across treatment lines. Patients discontinued for non-efficacy/safety reasons or treated with non-IBD doses or indications were excluded.

Results

228 IBD patients; 122 CD (Mean age 51,5, range 21-84) and 106 UC (Mean age 54,9, range 18-86) were enrolled. In CD (Picture 1) the third and fourth lines of treatment compared to the first line have the highest level of persistence, 96 (HR 2,6759; IC 95% 1,7803-4,0221) and 64 (HR 4,0229;IC 95% 2,0228-8,0006) months respectively. Vedolizumab had the highest persistence in the first and third line, 40 (IC 95% 15,750-61,000) and 39 (IC 95% 14,000-90,750) months respectively. In UC (Picture 2) the lines with a higher median of persistence are the second and third lines. The medians of persistence are greater for vedolizumab in all lines. Data on ustekinumab and tofacitinib need further observation.

Conclusion

Our study suggests that second-line biologics may offer benefits in terms of therapeutic continuity, likely due to improved efficacy and tolerability. These results encourage the use of second-line drugs earlier, to ensure sustained remission and potentially change the disease course.
P0990 Real-world effectiveness of upadacitinib induction therapy in Crohn’s disease, with a focus on patients with concomitant IMIDs
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 demonstrated efficacy across immune-mediated inflammatory diseases (IMIDs) and is approved or in development for conditions beyond Crohn’s disease (CD). Effective therapies are essential for managing CD, especially in complex cases involving multiple IMIDs. This study evaluates UPA as induction therapy in CD patients, focusing on outcomes for both CD and associated IMIDs.

Methods

This retrospective study at a Spanish tertiary care centre included adults with moderate-to-severe CD who initiated UPA in routine practice. Data on baseline characteristics, prior therapies, disease duration, and IMIDs were collected. The primary outcome was CD remission at week 12, assessed by Physician Global Assessment (PGA). Secondary outcomes included IMID remission by PGA, adverse events, and discontinuation.

Results

Thirty-four patients were included (mean age 45.5 years, 55.8% female, median CD duration 6 years). All had prior advanced therapy exposure, with 26.5% treated with at least three therapy lines. Ileal involvement was seen in 62%, with 30% showing upper GI involvement,24% stricturing disease and 56% had non-stricturing, non-penetrating disease. IMIDs were present in 35%, including psoriasis, juvenile idiopathic arthritis, uveitis, atopic dermatitis, spondyloarthritis, rheumatoid arthritis, and giant cell arteritis.

At week 12, 30.4% of CD patients achieved clinical remission, and 84.8% had at least a partial response. Among those with IMIDs, 33.3% achieved remission, with at least a partial response in 83.3%. In patients with both CD and IMIDs, 41.7% achieved remission in both conditions, and 75% showed at least a partial response in both.

Most patients (88%) began with a 45 mg/d dose, with 9% requiring extended induction (>12 weeks) at the same dose. Maintenance dosing was 30 mg in most cases, except for 6% who received a lower dose (15 mg). Discontinuation occurred in 32% of patients, primarily due to lack of response (54%) and adverse events (13%).

Conclusion

Upadacitinib (UPA) shows potential in improving both CD and associated IMIDs, with a notable proportion achieving remission or partial response in both conditions at 12 weeks. These findings suggest UPA may be a valuable option for managing complex cases with multiple IMIDs, though further research is needed to confirm efficacy and optimise treatment.
P0991 Laparoscopic ileocecal resection in pediatric Crohn’s disease: effect of anastomotic configuration on postoperative outcomes in the era of biologic therapy
Authors: Dotlacil V , Lerchova T , Kucerova B , Schwarz J , Hradsky O , Skaba R , Rygl M
Published: January 2025

Background

Postoperative complications and recurrence (POR) frequently follow Ileocecal resection (ICR) in pediatric Crohn’s disease (pCD) patients. Evidence addressing the effect of anastomosis type on complications and POR in children remains limited. We aimed to compare laparoscopic-assisted end-to-end (ETE), side-to-side (STS), and Kono-S anastomoses and evaluate their outcomes based on the followed parameters.

Methods

From April 2018 to December 2023, we prospectively collected data on anastomosis configuration, colonoscopy at 6 months post-surgery, perioperative and demographic parameters from all pediatric patients referred to ICR for pCD. Complications were classified according to the Clavien–Dindo classification (CDc). Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for endoscopic recurrence (ER), defined as Rutgeerts score >1. The ETE was set as the reference. Artificial Intelligence (AI) were not used in the production of this abstract.

Results

Thirty-eight patients (18 females, 47.4%) were included, 14 in ETE, 10 in STS, 14 in Kono-S. No preoperative differences were observed. Median surgery durations were 151 minutes for ETE, 142 for STS (p=0.78), and 169 for Kono-S (p=0.09). Complication rate did not significantly differ. Median hospitalisations were 6.5 days for ETE, 6 for STS (p=0.85), and 6 for Kono-S (p=0.70). Neither Kono-S nor STS showed a higher risk of ER compared to ETE, with OR=1.13 (95%CI=0.21-6.16) for STS and OR=0.41 (95%CI=0.09-1.87) for Kono-S.

Conclusion

Kono-S and STS anastomoses demonstrated comparable complication rates to ETE, without significantly prolonging hospitalization or operation duration. Neither type of anastomosis was associated with an increased risk of ER.
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

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 <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 >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<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

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 >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 >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

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 > 70 points) and clinical remission (CDAI < 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

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<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

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>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<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

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<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

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 <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

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

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<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<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<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.
P1038 Establishing a Tertiary-Level Inflammatory Bowel Disease Service in the UAE: A Response to Rising Incidence and Service Gaps
Authors: Omar N M , Alahmed M A , Ahmed E F , Kumar K K C , Quraishi M N
Published: January 2025

Background

Inflammatory bowel disease (IBD) is a growing public health concern in the Middle East, with the UAE experiencing a rapid rise in its incidence. Due to the predominance of private healthcare facilities, dedicated IBD services are exceedingly rare, and care is often fragmented. We outline the key initiatives undertaken to establish one of the few structured and comprehensive IBD services in the region.

Methods

Post-2023, our hospital initiated targeted changes to establish a tertiary care IBD service in the UAE. Through an analysis of service modifications and organizational strategies, we detail efforts to improve care delivery towards providing excellence in IBD care.

Results

The introduction of a structured care model has significantly improved IBD outcomes through a dedicated team of IBD-trained physicians, IBD clinical nurse specialist (CNS), and an administrator. Multidisciplinary meetings have standardized care, enabling early diagnosis, initiation and optimisation of advanced therapies (AT). The service has notably reduced corticosteroid use, indicating effective disease control. A growing comprehensive IBD registry now prospectively tracks over 320 patients on AT, providing valuable data for clinical and research needs. High-risk patient lists and virtual flare clinics have decreased hospital admissions by nearly 90%, facilitating proactive management. The service has early adoption of novel ATs and is supported by an active clinical trials program. Early initiation of AT, particularly for moderate to severe Crohn’s disease, has reduced the median time to treatment from diagnosis to 1.54 months (IQR 2.23) in 2024. Holistic IBD clinics, with access to a specialist dietitian and psychologist, have improved patient satisfaction and outcomes. CNS-led initiatives, including educational sessions on medication use, disease management, preconception and pregnancy care have significantly boosted patient engagement and health outcomes. Patient support and advocacy groups have been established, providing a platform for education and shared experiences. Additionally, Arabic versions of disease and AT patient information leaflets have been developed to enhance accessibility and understanding. Advanced IBD endoscopy, including chromoendoscopy, is now offered as standard care.

Conclusion

The establishment of a structured, multidisciplinary IBD service has transformed care delivery, addressing critical gaps in the regional healthcare landscape. Key initiatives have led to improved clinical outcomes, reduced hospital admissions, and enhanced patient satisfaction. This model serves as a benchmark for comprehensive IBD care in the region, demonstrating the impact of specialized, patient-centred services.
P1039 An Evaluation of Anti-IL23 Therapy in Primary Sclerosing Cholangitis Associated Inflammatory Bowel Disease
Authors: Al-Shakhshir S , Morris S , Kaur S , Culver E , Elzubeir A , Rushbrook S , Nayagam J S , Joshi D , Hernandez-Evole H , Schregel I , Schramm C , Rodriguez S , Leibovitzh H , Shibolet O , Cristoferi L , Vigano C , Carbone M , Invernizzi P , Trivedi P
Published: January 2025

Background

The majority of patients with primary sclerosing cholangitis (PSC) have inflammatory bowel disease (IBD). This association has fostered several pathogenic hypotheses linking mucosal immunity to hepatobiliary inflammation. A putative therapeutic target along this axis centres on gut-derived IL-17 secretor cell subtypes, which are activated by interleukin (IL)23. Notably, emergent forms of IBD treatment host several anti-IL23 agents, however safety and efficacy data in PSC patients is limited.

Methods

We conducted a multi-centre study, evaluating treatment experiences with Ustekinumab (a dual anti-IL12/23 agent), Risankizumab, and Mirikizumab (anti-IL23 alone). Data was analysed to determine treatment impact on liver biochemistry; IBD response defined by serial Mayo colitis scores or faecal calprotectin (FCP) values; and treatment-emergent adverse events.

Results

Data was accrued across eight centres from 66 pts (Ustekinumab, 62; Risankizumab, 4 [n=1 escalated from Ustekinumab] and Mirikizumab, 1) with median treatment time of 9 months (IQR 5-24). The majority of patients were men (63%; n=42) with a median age at PSC diagnosis of 24y (IQR 17-36). The predominant PSC phenotype was large duct (73%; n=49), with two patients having cirrhosis, 13% (n=7) being transplant recipients, and 66% (n=44) having an IBD phenotype consistent with ulcerative colitis. At baseline, the median FCP and Mayo colitis scores were 810ug/L (IQR 369-1727; n=33/66) and 5 (IQR3-8; n=31/66), respectively. 60 patients were commenced on these agents as 2nd-4th line, after failure of prior biologic therapy. In all, IBD response was observed in 15% (n=8/52) at 6 months, 20% (n=7/35) at 12 months and 21% (n=4/19) at 24 months. Remission was achieved in 3 pts (4.5%) at 18 months. Among non-transplant patients, the median change in ALP from baseline to 6 months was not significant (ALP x upper limit of normal [ULN] 1.4 vs. 1.2; p=0.67), nor from baseline to 12 (ULN 1.1 vs. 1.1; p=0.161) or 24 months (ULN 1.6 vs. 1.0; p=0.074) (Figure 1). No significant differences in serum ALT or bilirubin were observed from baseline to 6, 12 or 24 months. Treatment was discontinued in 37% (n=25/67) due to lack of efficacy and in one patient due to an adverse event.

Conclusion

Anti-IL23 agents are safe and well-tolerated in PSC-IBD. However, IBD response and remission rates appear to dwarf those seen in IBD alone, with no significant effects on liver biochemistry.
P1041 Efficacy and Safety of Adalimumab Biosimilar Dose Escalation Treatment in biologic naïve Patients With fistulas Crohn’s Disease: A Prospective, Single-Arm Clinical Practice
Authors: Cheng Y , Wang H , Yu Q , Zhu L
Published: January 2025

Background

The introduction of tumor necrosis factor (TNF) inhibitors, including adalimumab, has dramatically changed the treatment landscape for moderate-to-severe Crohn’s disease (CD). The availability of biosimilars has minimized the economic burden on patients and reduced global health inequalities while ensuring efficacy. However, the efficacy of adalimumab biosimilars for fistula CD is unclear.

Methods

Sixty patients with fistulas CD from July 2021 to July 2023 were included, and all of them were treated with adalimumab biosimilar treatment for 12 weeks (subcutaneous injection of 160 mg in the 0th week, 80 mg in the 2nd week, and 40 mg from the 4th to the 12th week), and the decision of whether to receive adalimumab conventional therapy (40 mg q2w) or incremental therapy (80 mg q2w) was made based on the patients’ traumatic response at the end of the 12-week period. The decision to follow up with regular (40 mg q2w) or incremental (80 mg q2w) treatment of adalimumab was made based on wound response after 12 weeks, and the dosage was again adjusted according to efficacy after 24 weeks, and the patients were followed up to 52 weeks. The primary outcome of this study was the fistula healing rate at 52 week. Secondary outcomes were fistula response rate, endoscopic response rate and endoscopic remission rate.

Results

A total of 60 patients with active fistula-type Crohn’s disease were enrolled in the study. Most of the enrolled patients were in the middle-aged and young age group, with a mean age of (26.8±9.5) years, 75.5% males, CDAI score (180.9±97.62), SES-CD score (15.69±7.79), and PDAI score (4.58±2.12). In the conventional treatment group, the fistula response rate was 57.89%, 65.22% and 73.91% at 12, 24 and 52 weeks, respectively; the fistula healing rate was 55.26%, 69.57% and 65.22%, respectively; the endoscopic response rate was 60.53%, 82.61% and 100%, respectively; and the endoscopic relief rate was 36.84%, 73.91% and 86.96%, respectively. In the incremental treatment group, the fistula response rate was 12.5%, 66.67% and 66.67% at 12, 24 and 52 weeks, respectively; the fistula healing rate was 12.5%, 66.67% and 0, respectively; the endoscopic response rate was 50%, 66.67% and 66.67%, respectively; and the endoscopic remission rate was 0, 0 and 16.67%, respectively. All patients had no adverse drug reactions or serious infections during treatment.

Conclusion

In the real world, adalimumab biosimilar dose escalation treatment may somewhat improve fistula response rates and endoscopic response rates in fistulous CD patients initially treated with biologics, but has a limited effect on fistula healing rates and endoscopic remission rates.
P1042 Effectiveness and safety of vedolizumab in real-world studies in Chinese patients with inflammatory bowel disease: a systematic review and meta-analysis
Authors: Gu Y , Zhang X , Gu L , Zou D
Published: January 2025

Background

Inflammatory bowel diseases (IBD), consisting of Crohn’s disease (CD) and ulcerative colitis (UC), are chronic gastrointestinal conditions with increasing prevalence in China. Vedolizumab (VDZ), a humanized monoclonal antibody that targets α4β7 integrin, has been approved for use in China since 2020. This systematic review and meta-analysis aimed to evaluate the real-world effectiveness and safety of VDZ in Chinese patients with IBD.

Methods

A systematic literature search was conducted on 20th Dec 2023 to identify real-world studies evaluating intravenous VDZ in Chinese patients with IBD. Meta-analyses were performed separately for CD and UC patients using a random-effects model in R software to pool clinical remission and response rates, and endoscopic remission rates across induction (6-14 weeks), medium term (22-30 weeks), and long term (over 48 or 52 weeks). Subgroup analysis was conducted based on the history of biologics. Incidence of adverse events (AE), serious AE (SAE), and serious infection was assessed for safety.

Results

A total of 20 studies (12 CD, and 15 UC), involving 1472 patients (610 CD, and 862 UC), were included in the analysis (Figure 1). During the induction phase, a clinical response and clinical remission were achieved by 71.31% and 75.58% of CD patients, and 67.89% and 46.46% of UC patients, respectively. In the medium term, 64.32% of CD patients and 65.72% of UC patients achieved a clinical response, while 60.72% of CD patients and 60.95% of UC patients achieved clinical remission. In the long term, clinical response rates were 57.14% in CD patients and 73.50% in UC patients, while clinical remission rates were 51.28% and 60.84% for CD and UC patients, respectively.

For the endoscopic remission, there were 11.11%, 18.41%, and 36.42% of that in CD patients, and 44.58%, 53.32%, and 62.40% of that in UC patients were achieved in the induction, medium term, and long term. Subgroup analyses indicated that both bio-naïve and bio-exposed patients, in both UC and CD groups, showed relatively favourable outcomes across the available time points (Table 1).

Adverse events (AEs) were reported in 6.67% to 61.54% of CD patients, and 29.69% to 75.38% of UC patients. Serious adverse events (SAEs) and serious infection rates ranged from 0.00% to 1.56%, and 0.00% to 2.70%, respectively, in UC patients, while neither SAE nor serious infections were reported in the CD studies.

Conclusion

VDZ demonstrated favourable effectiveness in Chinese patients with IBD across induction, medium- and long-term treatment periods, with a good safety profile.
P1045 Treat-smart study: Leveraging individual inflammatory markers for personalized therapy in patients with IBD
Authors: Medhat M , Ramadan Y N , Hashem M , Doaa A , Nariman Z , Hetta H F ,   “Assiut Tropical IBD Study Group” (ATISG)
Published: January 2025

Background

Diverse patient responses to treatment challenge the management of inflammatory bowel disease (IBD). This study aims to evaluate if there are differences in the inflammatory mediators among IBD patients and the treatment outcome concerning these variations.

Methods

This study was conducted in the IBD clinic at AL-Rajhi Hospital, Assiut University. The concentrations of TNF-α and IL-12/23 (p40) were measured in IBD patients and healthy controls using enzyme-linked immunosorbent assay (ELISA) technique. In IBD patients, marker levels were assessed before and after induction of biological therapy to evaluate changes in their levels. Biological therapies were prescribed according to the treatment protocols of the funding entities (such as health insurance). The investigators did not know the levels of inflammatory markers at the time of treatment prescription.

Results

From May 23, 2023, to July 16, 2024,18 IBD patients were enrolled in this study. Half of the study population were males with a median age of 27 years. The cohort included 16 patients with Ulcerative Colitis and 2 with Crohn’s disease, as shown in table 1. Before enrollment, 9 patients had failed to achieve remission on conventional therapy, and 9 had also failed on both conventional and first-line biological therapies. The analysis of the inflammatory markers at baseline showed significant variation among patients. Third of the patients (6 out of 18) showed only elevation in the TNF- α, one patient had only elevated IL 12/23, and the rest had combined elevation of both markers. Among patients with TNF-α as the predominant pathway, remission was achieved in all patients given anti-TNF-α therapy (5 out of 6 patients). In contrast, one patient with IL12/23–dominant group failed to achieve remission after receiving Ustekinumab. In the same context, another patient with elevated IL-12/23 alone failed to respond after receiving anti-TNF-α treatment. Patients with elevated levels of both TNF-α and IL 12/23 (11 patients) exhibited mixed responses. Among those treated with anti-TNF-α, only 1 achieved remission, while 7 experienced treatment failure. Using Ustekinumab in this subgroup led to remission in only 1 out of 3 cases, as shown in figure 1.

Conclusion

These results showed that treatment response is significantly influenced by the predominant inflammatory pathway expressed in patients with IBD. Specifically, patients with TNF-α dominant pathway showed a high remission rate with anti-TNF-α therapy. Conversely, non-specific treatments were less effective, emphasizing the importance of targeted therapy. Patients with dual-marker elevation may have better responses by combo therapy or JAK inhibitors. These results may pave the way for tailored treatment for IBD patients.
P1051 Establishment and Validation of Prediction Models for Short-term and Long-term Effectiveness of Ustekinumab in Patients with Crohn’s Disease
Authors: Su T , Wu H , Zhi M , Yao J
Published: January 2025

Background

Ustekinumab (UST), a novel biological agent for Crohn’s disease (CD), has shown efficacy in CD patients. Our objective was to establish clinical prediction models to accurately forecast the short- and long-term effectiveness of UST in individuals diagnosed with CD.

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 from May 2020 to July 2023. The patients were assigned in a 7:3 ratio at random to the training cohort and the validation cohort. Predictors were compressed through the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. Logistic regression analysis was used to create the final prediction models.

Results

A total of 464 patients with CD were included in the statistical analysis, 171 of whom had complete endoscopic data. Four models were constructed: two to predict the probability of clinical or endoscopic remission at week 16 or 20 based on baseline data, and two to predict the probability of clinical or endoscopic remission at week 52 based on data obtained at week 16 or 20. The C-index was 0.714, 0.866, 0.814 and 0.841, respectively. Because of poor calibration, we constructed another model to predict the probability of endoscopic remission at week 52 based on baseline data (C-index:0.748). In the internal validation, the above models showed good performance.

Conclusion

We have constructed several models to predict the short- and long-term effectiveness of UST in patients with CD, promising to be a simple and practical clinical tool.