bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0590 Long term outcomes of biologic therapy for the treatment of prepouch ileitis: a multi-centre multi-national retrospective study
Authors: Ghersin I , Calini G , Koifman E , Segal J , Argyriou O , McLaughlin S , Johnson H , Rottoli M , Sahnan K , Warusavitarne J , Hart A 
Published: January 2025

Abstract

Background
Prepouch ileitis (PPI) is inflammation of the ileum proximal to an ileoanal pouch, usually associated with pouchitis. The treatment of PPI as a specific entity is poorly studied, and long-term follow-up data are lacking.
We aimed to describe the long term outcomes of biologic therapy in a large, multi-centre multi-national cohort of PPI patients.

Methods
This was an observational, retrospective, multi-centre, multi-national study.
We included patients with an endoscopic diagnosis of PPI, treated with biologic medications, who had a follow up of at least 1 year.
The primary outcome was first line biologic treatment persistence, defined as continuation of the biologic treatment throughout the study period. Secondary outcome was pouch failure, defined by the need for a defunctioning ileostomy or pouch excision.

Results
There were 55 patients in our cohort. Males comprised 58.2% of our cohort (32/55). Average patient age was 57, and average age at UC diagnosis was 25.1. Average follow up length was 113.2 months (range 20 - 236 months)
Infliximab was first line treatment in 33 patients (60%), while 20 (36.3%) initially received Adalimumab and 2 (3.7%) received Vedolizumab treatment.
Second line advanced medical treatments in our cohort included infliximab (2 patients), adalimumab (12 patients), vedolizumab (10 patients), ustekinumab (6 patients) and upadacitinib (1 patient).
At the end of the study period only 9 out of 55 patients (16.4%) were still on first line biologic treatment. Persistence rates for infliximab (5/33, 15.1%) and adalimumab (3/20, 15%) were similar (p=0.99). Out of the 46 patients failing first line biologic treatment, 22 (40% of the cohort) developed pouch failure, and 24 (43.6% of the cohort) are currently treated with a different medical therapy.

Conclusion
First line biologic treatment for PPI is associated with low long term persistence rates. A significant percentage of PPI patients initially treated with biologics develop pouch failure.
P0594 Efficacy and safety of etrasimod in Japanese UC patients: results of a phase 2 dose-ranging study
Authors: Takeuchi K , Nakase H , Hisamatsu T , Matsuoka K , Arai S , Yuasa H , Oe M , Ono R , Keating M , Gu G , Lazin K , McDonnell A , Fokuta K , Hibi T 
Published: January 2025

Abstract

Background
Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). The efficacy and safety of etrasimod 1 mg and 2 mg have been assessed in a global population,1 but not in a Japanese population. We evaluated the efficacy and safety of etrasimod 1 mg and 2 mg in Japanese patients with moderately to severely active UC over a 12-week period.

Methods
This was a multi-centre, double-blind, placebo-controlled, phase 2 trial among Japanese patients with moderately to severely active UC (NCT05061446). Patients were randomised 1:1:1 to receive either 1 mg or 2 mg of etrasimod once daily or placebo. The primary efficacy endpoint was the proportion of patients achieving clinical remission at Week 12. Secondary efficacy endpoints included the proportion of patients achieving endoscopic improvement, symptomatic remission, endoscopic improvement-histologic remission, clinical response and endoscopic normalisation. Efficacy analyses were based on the full analysis set (FAS) of patients with a modified Mayo score of 5–9.The occurrence and severity of treatment-emergent adverse events (TEAEs) were also assessed.

Results
The FAS comprised 54 patients (placebo: N=18 [33.3%]; etrasimod 1 mg: N=17 [31.5%]; etrasimod 2 mg: N=19 [35.2%]). The mean (standard deviation) age of all patients was 43.3 (12.5) years. At baseline, 11 (20.4%) patients were receiving corticosteroid treatment. At Week 12, clinical remission was achieved by one (6.7%) patient receiving etrasimod 1 mg, five (26.3%) patients receiving etrasimod 2 mg and no patients receiving placebo (Figure). At Week 12, more patients receiving etrasimod vs placebo achieved secondary endpoints, except endoscopic normalisation, which no patients achieved. Etrasimod was generally well tolerated. TEAEs were experienced by nine (52.9%) patients receiving etrasimod 1 mg, 13 (68.4%) patients receiving etrasimod 2 mg and 10 (55.6%) patients receiving placebo (Table). All TEAEs were mild to moderate in severity. Two patients in the placebo group and none in the etrasimod 1 mg or 2 mg groups discontinued the study due to TEAEs.

Conclusion
Etrasimod 2 mg was effective and well tolerated in Japanese patients with moderately to severely active UC. More patients receiving etrasimod 2 mg met primary and most secondary efficacy endpoints than those receiving 1 mg. All TEAEs were mild to moderate in severity with safety consistent with that previously observed.1

References
1. Sandborn WJ et al. Gastroenterology 2020; 158: 550–561.
Pfizer’s generative artificial intelligence tool MAIA was used to assist production of the abstract first draft. Authors reviewed/edited and take responsibility for the content.
P0596 Fecal bile acids predict the therapeutic effect of biological agents in patients with ulcerative colitis
Authors: Guo J , Yuan X , Li C , Zhang X 
Published: January 2025

Abstract

Background
Ulcerative colitis (UC) is a chronic non-specific inflammatory disease of the colon. Infliximab or vedolizumab is recommended for treatment of moderate to severe UC, but has a primary or secondary non-response rate. Receiving early predictions on treatment efficacy can offer substantial support for patients’ therapeutic interventions. We aim to use fecal bile acids to identify predictive biomarkers.

Methods
Fecal samples were collected from 55 UC patients hospitalized in the Second Hospital of Hebei Medical University and 10 healthy volunteers. UC patients were divided into clinical response group and clinical non-response group according to the therapeutic effect of biologics. Quantitative detection of target bile acids was performed on fecal samples. The bile acid levels of the two groups were compared, and the bile acids that predicted the therapeutic effect were screened by orthogonal partial least squares discriminant analysis (OPLS-DA) and the analysis of receiver working characteristic curve.

Results
Compared with healthy adults, patients with UC showed decreased total fecal bile acids, increased primary bile acids, and decreased secondary bile acids. After treatment with biologics, there was a decrease in primary bile acids and an increase in secondary bile acids. In comparison between clinical responders and non-responders, fecal lithocholic acid and deoxycholic acid were significantly increased, and the ratio of primary bile acids to secondary bile acids was significantly decreased. When deoxycholic acid was higher than 29.55 ug/g or lithocholic acid was higher than 0.195 ug/g, it had predictive value for clinical response.

Conclusion
Fecal bile acids, especially deoxycholic acid and lithocholic acid, may serve as novel biomarkers for predicting the therapeutic effect of biological agents in UC patients.

References
[1]Li N, Zhan S, Tian Z, et al. Alterations in bile acid metabolism associated with inflammatory bowel disease. Inflamm Bowel Dis, 2021, 27(9): 1525-1540.
[2]Ding NS, McDonald J, Perdones-Montero A, et al. Metabonomics and the gut microbiome associated with primary response to anti-TNF therapy in Crohn’s disease. J Crohns Colitis, 2020, 14(8): 1090-1102.
[3]Lee J, Plichta D, Hogstrom L, et al. Multi-omics reveal microbial determinants impacting responses to biologic therapies in inflammatory bowel disease. Cell Host Microbe, 2021, 29(8): 1294-1304.e4.2.
P0598 Feasibility and limitations in adopting treat-to-target approach in inflammatory bowel diseases (IBD): real-life scenario
Authors: Harindranath S , Desai D C , Mehta N , Abraham P , Gupta T , Dhoble P , Mehendale S 
Published: January 2025

Abstract

Background
Physician and patient acceptance of the T2T approach is not universal.1,2 We prospectively studied the (a) proportion of patients with IBD achieving T2T response (STRIDE II consensus); (b) patient-, disease- and physician-related factors affecting feasibility of T2T approach.

Methods
Patients with IBD were followed up for clinical, biomarker, endoscopic, radiologic and histologic response, as defined in the revised T2T guidelines.3 In whom it was not achieved, possible responsible factors were studied.

Results
160 patients were enrolled – Crohn’s disease [CD] 73 (39 males, age mean (IQR) 38.6 (±14.3) years; L1-27, L2-20, L3-26; B1-31, B2-33, B3-7; perianal disease 12); ulcerative colitis [UC] 87 (39 males; age mean (IQR) 41.38 (±15.6) years ; E1- 4, E2-27, E3-56). Median disease duration was 48 (IQR 24-120) months and median follow-up 4 (IQR 3-5.5) months.Table shows various targets achieved
Limiting factors to achieving T2T (103 patients): physician related factors occurred in 39 (37%) (failure to confirm endoscopic remission in 20 and failure to step up therapy in 19 patients); patient related factors in 36 (34.9%) (nonadherence in 16 and no follow up endoscopy /imaging in 20 patients); disease related factor (treatment non response) in 28 patients (27.8%).

Conclusion
Clinical remission occurred in 47% in UC and 27% in CD. A complete treat-to-target (T2T) response according to the STRIDE-II consensus could be achieved in only 16.8% of patients. Patient, physician and disease related factors contributed equally for non-achievement of T2T

References
1.Bryant RV, Costello SP, Schoeman S, et al. Limited uptake of ulcerative colitis “treat-to-target” recommendations in real-world practice. J Gastroenterol Hepatol. 2018;33:599-6072.
2.Selinger C, Carbonell J, Kane J, Omer M, Ford AC. Acceptability of a ‘treat to target’ approach in inflammatory bowel disease to patients in clinical remission. Frontline Gastroenterol. 2020;12: 30-38
3.Turner D, Ricciuto A, Lewis A, et al. STRIDE-II: an update on the Selecting Therapeutic Targets In Inflammatory Bowel Disease (STRIDE) initiative of the International Organization for the Study of IBD (IOIBD): determining therapeutic goals for treat-to-target strategies in IBD. Gastroenterology. 2021; 160: 1570–8.
P0606 The efficacy of upadacitinib in Intestinal Behçet’s Disease refractory to anti-TNF-α therapy in a retrospective study
Authors: Lu J , Fang Y , Du J , Chen C 
Published: January 2025

Abstract

Background
Behçet’s syndrome is a chronic, systemic vasculitis that affects multiple organs, with intestinal involvement referred to as intestinal Behçet’s disease. The understanding of effective treatments for this condition remains limited. Anti-tumor necrosis factor-α (TNF-α) therapy is recommended for moderate to severe or refractory cases. However, managing patients unresponsive to anti-TNF-α therapy presents a significant clinical challenge. Upadacitinib, a Janus kinase (JAK) inhibitor, has not previously been studied in this context. This study aims to evaluate the efficacy of upadacitinib in patients with anti-TNF-refractory intestinal Behçet’s disease.

Methods
We retrospectively included patients with refractory intestinal Behçet’s disease treated with upadacitinib at the First Affiliated Hospital of Zhejiang University School of Medicine. Data collected included clinical manifestations, medication history, physical examination findings, laboratory results, and endoscopic evaluations before and after treatment.

Results
Six patients with intestinal Behçet’s disease were included, five of whom were female, with an average age of 35.5±11.0 years. All patients presented with recurrent oral ulcers and abdominal symptoms, accompanied by endoscopic evidence of ileocecal ulcers. They had previously failed treatment with corticosteroids, immunosuppressants, and at least one anti-TNF-α biologic agent. Following 6.1±2.1 months of upadacitinib treatment, all patients showed clinical symptom improvement or relief. Compared to baseline, hemoglobin levels increased (107.2±11.3 vs. 127.5±7.9, P=0.030), serum albumin levels improved (39.2±4.0 vs. 47.2±1.4, P=0.009), C-reactive protein levels decreased (39.9±37.4 vs. 3.0±3.4, P=0.048), and Endoscopic performance improved (P=0.026). No serious adverse events were reported in either of the 6 patients during follow-up.

Conclusion
Upadacitinib appears to be a promising therapeutic option for patients with intestinal Behçet’s disease refractory to anti-TNF-α therapy.
P0613 Obesity is associated with inferior treatment outcomes in inflammatory bowel disease: a nationwide Dutch registry study
Authors: Oomkens D , Mujagic Z , de Vries A , van der Meulen-de Jong A , Straatmijer T , Löwenberg M , van der Marel S , West R , Bodelier A , van Schaik F , Visschedijk M , Duijvestein M ,   Initiative on Crohn and Colitis
Published: January 2025

Abstract

Background
The impact of overweight and obesity on treatment outcomes in inflammatory bowel disease (IBD) remains unclear, as current literature is inconclusive and often restricted to selected patient populations. We examined the effect of Body Mass Index (BMI) on response to treatment in patients with IBD starting various treatments.

Methods
Patients ≥ 16 years old with IBD, a documented baseline BMI, and starting thiopurines and allopurinol, intravenous (iv) vedolizumab, subcutaneous (sc) vedolizumab, ustekinumab, ozanimod, filgotinib, or tofacitinib were selected from the Dutch Initiative on Crohn and Colitis (ICC) registry. Underweight patients (BMI &lt; 18.5 mg/kg2) were excluded. The primary outcome was steroid-free clinical remission (i.e. Simple Clinical Colitis Activity Index (SCCAI) ≤ 2 for ulcerative colitis (UC) and IBD-unclassified (IBD-U), and Harvey Bradshaw Index (HBI) &lt; 5 for Crohn’s disease (CD)) at week 12 and 24. Outcomes were compared between normal weight (BMI 18.5-25 kg/m2), overweight (BMI 25-30 kg/m2) and obese (BMI ≥ 30 kg/m2) patients using binary logistic regression analyses.

Results
A total of 1066 IBD patients (616 CD, 432 UC, and 18 IBD-U) were included: 619 had normal weight, 303 were overweight, and 144 were obese. At week 12, overweight patients were more frequently in steroid-free clinical remission (49.8%, OR = 1.452, 95% CI: 1.082-1.947, p = 0.013) compared to normal weight patients. Multivariable regression adjusting for age, smoking, prior vedolizumab use, and baseline corticosteroids confirmed higher odds of steroid-free clinical remission in overweight patients (OR = 1.369, 95% CI: 1.010-1.856, p = 0.043). At week 24, obese patients were less frequently in steroid-free remission (35.3%, OR = 0.578, 95% CI: 0.380-0.879, p = 0.010), with multivariable analysis also indicating lower odds of steroid-free clinical remission in obese patients (OR = 0.537, 95% CI: 0.346-0.832, p = 0.005). A logistic mixed-effects model demonstrated a different course of steroid-free clinical remission rates over time from baseline to week 24 between the BMI groups, which is shown in Figure 1, with a near-significant overall interaction effect (p = 0.061).

Conclusion
Obesity was associated with lower steroid-free clinical remission at week 24. Surprisingly, at week 12, overweight was associated with a higher rate of steroid-free clinical remission. However, despite this apparent faster treatment response, this advantage disappeared at 24 weeks.
P0619 Comparative efficacy of all available pharmaceutical therapies for moderate to severe Crohn’s disease: a systematic review and network meta-analysis
Authors: Versteegh M , Idema D , Huygens S , Jenniskens K , Pierik M , Römkens T , van Schaik F , Wahab P , Huis in ‘t veld L , Kusters M , van der Braak K , Hooft L , Damen J 
Published: January 2025

Abstract

Background
The therapeutic landscape for Crohn’s disease (CD) has expanded, offering patients increased treatment possibilities, but with limited comparative evidence.This study provides compare efficacy and discontinuation rates of all pharmaceutical therapies - old and new - in moderate-to-severe CD.

Methods
We conducted a systematic review (until October 2023) and network meta-analyses (NMA) of phase-III randomized controlled trials (RCTs) on the efficacy of pharmaceutical therapies for induction of clinical response, clinical remission and maintenance of clinical remission. Furthermore, drug discontinuation rates were assessed. Frequentist NMA results and SUCRA rankings were reported for biological-naive and -exposed patients.

Results
The search resulted in 3017 references, of which 77 RCTs were included. Networks were sparse and therapies had overlapping confidence intervals. In biological-naive patients, adalimumab (high induction regimen) had the highest SUCRA ranking for induction of clinical remission, and infliximab/azathioprine combination therapy had the highest SUCRA ranking for maintenance of remission. Among immunomodulators, methotrexate had the highest ranking for induction and azathioprine for maintenance of remission. In biological-exposed patients, upadacitinib had the highest SUCRA ranking for induction and maintenance of clinical remission. Adverse event related discontinuation was numerically highest for methotrexate, azathioprine and upadacitinib.

Conclusion
This NMA including immunomodulators, biologicals and small molecules, suggests that anti-TNF (combination)therapy is most efficacious in biologic-naive patients and upadacitinib in biologic-exposed patients. Differences in relative risks were small and confidence intervals overlapping suggesting that no claims to superiority can be made. Conventional therapies remain important in the treatment algorithm for CD patients despite the advent of advanced therapies.
P0623 Vedolizumab clearance as a predictor of remission in inflammatory bowel disease: a real-world pharmacokinetic study
Authors: Markovic S , Kralj D , Knezevic Ivanovski T , Kalaba A , Odanovic O , Homsek A , Svorcan P , Vucicevic K ,   OPTYMAB studygroup
Published: January 2025

Abstract

Background
Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), requires sustained control of gastrointestinal inflammation to improve patient outcomes. Vedolizumab (VDZ), a monoclonal antibody, has been approved for the induction and maintenance of remission in moderate to severe UC and CD. However, interpatient variability in VDZ pharmacokinetics (PK) complicates therapeutic drug monitoring (TDM). This study aimed to assess whether VDZ clearance (CL) could serve as a surrogate marker for remission, outperforming trough concentrations as a predictor.

Methods
This retrospective cohort study analysed 106 patients (61 UC and 45 CD) receiving 300 mg VDZ therapy at variable intervals (4, 6, or 8 weeks) after standard induction. Blood samples were collected at trough times, and VDZ concentrations were measured using ELISA. A population PK model was developed using NONMEM (version 7.5) to estimate VDZ CL. Statistical analyses included Fisher’s exact, t-test, and logistic regression to evaluate clinical predictors, while ROC curve analysis identified optimal cut-offs for clinical and endoscopic outcomes.

Results
A two-compartment model best described the PK of VDZ. The estimated CL was 0.159 L/day, increasing by 26.4% in patients previously treated with anti-TNF agents. Higher CL values correlated with thrombocytosis (Plt &gt; 350·10^3/µL, AUROC = 76.9, 95% CI 62.8–91.1) and were significantly associated with reduced likelihood of remission. VDZ trough levels did not predict remission outcomes as effectively as CL, suggesting that AUC-based exposure metrics may better indicate clinical response.

Conclusion
This study demonstrates that VDZ CL, influenced by prior anti-TNF exposure and inflammatory markers, is a more reliable predictor of clinical and endoscopic remission than trough concentration. These findings support the integration of CL-based TDM for VDZ to optimize therapeutic outcomes in IBD management. Further research on AUC-based metrics may provide enhanced TDM guidance.

References
1.Feagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369:699–710.
2.Sandborn WJ, Feagan BG, Rutgeerts P, et al. Vedolizumab for Crohn’s disease. N Engl J Med. 2013;369:711–21.
3.Dreesen E, Verstockt B, Bian S, et al. Evidence to support monitoring of vedolizumab trough concentrations in IBD. Clin Gastroenterol Hepatol. 2018;16:1937-1946.
P0625 Impact of TMPT genotype on Azathioprine side effects and durability in a cohort of pediatric patients with Inflammatory Bowel Diasease: a real life study
Authors: Di Sario F , Galeazzi T , Castaldo P , Magi S , Franceschini E , Gatti S 
Published: January 2025

Abstract

Background
Genetic variations in the thiopurine S-methyltransferase (TPMT) gene have been associated with adverse events (ADRs) to Azathioprine (AZA). This study aims to investigate the prevalence of TPMT polymorphisms and their correlation with AZA toxicity and treatment durability in a cohort of pediatric patients with inflammatory bowel disease (IBD).

Methods
A total of 104 IBD patients (47% males, 53% females), of which one had indeterminate colitis, 56 had Crohn ‘s disease and 47 had ulcerative colitis, with a mean age at diagnosis of 11±3.7 years, were genotyped for TPMT*2, TPMT*3A, TPMT*3B, and TPMT*3C. Data on AZA related side effects, dosage, and treatment durability were recorded.

Results
Of the 104 patients, six (5.7%) had TPMT mutations: three carried the TPMT *3A variant, one the TPMT *3B variant, and two the TPMT *3C variant (Figure 1).
Among the 104 patients, 94 (90%) started on AZA treatment. Among the 86 patients who started AZA with at least 6 months of follow-up, 18 (20.9%) developed ADRs, primarily pancreatitis (9.3%) and myelotoxicity (8%) (Figure 2).
Of the 6 patients with mutations, only one developed ADRs, showing no significant difference from the total population. AZA withdrawal due to ADRs occurred in 18.7% of the population, with no significant differences between the two groups. At the start of therapy and after 12 months, the mean AZA dosage (mg/kg/day) was lower in mutated patients compared to wild-type patients, though this difference did not reach statistical significance (1.35±0.51 vs 1.67±0.4, p=0.12; 12 1.74±0.35 vs 2.1±0.45, p=0.09 respectively).

Conclusion
In this cohort of IBD subjects, no significant association was observed between TPMT polymorphisms, the occurrence of thiopurine-related ADRs, and the durability of AZA treatment. This suggests that screening for TPMT variants does not impact the likelihood of patients developing ADRs.