bluuebunny/crossref_metadata_2025 huggingface dataset:
P0575 Bronchiectasis in patients with inflammatory bowel disease – prevalence, predictors, and clinical characteristics
Authors: Freund O , Bar-Shai A , Alkhazov A , Stav D , Hadad Y , Perluk T M , Sror N , Hirsch A , Ron Y , Thurm T , Herling A , Leibovitzh H , Maharshak N , Cohen N A
Published: January 2025

Background

Inflammatory bowel diseases (IBD) are known to be associated with bronchiectasis (BE). However, data detailing the prevalence of BE among patients with IBD (IBD-BE), its risk factors, and clinical characteristics are limited.

Methods

This was a single center retrospective study including patients who visited an IBD unit at a tertiary center between 2022 and 2023. Data on prior chest CT scans was extracted. Radiologists blinded to clinical data analyzed all chest CT scans for BE. The overall prevalence of IBD-BE was estimated using multiple imputation analysis. Risk factors were analyzed in the whole cohort and after matching.

Results

1637 patients with IBD were included, 254 had prior chest CT scans, of these, 30 (1.8% of the cohort) had BE. The estimated overall prevalence of IBD-BE was 4.7% (95% CI 3.6-5.8%). Demographic and clinical characteristics are detailed in Table 1. In a multivariate logistic regression analysis, older age (adjusted odds ratio (aOR) 1.04, 95% confidence interval (CI) 1.02-1.06 for every additional year, p<0.001), UC diagnosis (aOR 2.31, 95% CI 1.08-4.92, p=0.029), and IBD-related surgery (aOR 2.71, 95% CI 1.23-5.96, p=0.013) remained independent predictors for IBD-BE. The IBD-BE group also had more extraintestinal manifestations (EIMs) in general (57% vs. 31%, p=0.01), and specifically arthritis (33% vs. 14%, p=0.02) and non-arthritis (33% vs. 19%, p=0.1) involvement. Radiological and clinical features of patients with IBD-BE are detailed in Figure 1. Interestingly, of patients with IBD-BE, 63% had evidence of BE in the chest cuts of their prior abdominal CT scans, and 70% had relevant respiratory symptoms. Despite this, most did not see a pulmonologist nor receive BE-related therapy. Clinical characteristics and outcomes of IBD-BE were similar to those of patients with non-IBD-related BE.

Conclusion

This study shows a minimal prevalence of 1.8% and an estimated 4.7% overall prevalence of BE in patients with IBD. Risk factors associated with IBD-BE included older age, a diagnosis of UC, IBD-related surgery and the presence of EIMs. The low rates of BE-directed therapy and pulmonology referral indicate the need for a higher degree of suspicion and timely referral.
P0586 Nationwide population-based cohort study on the use and persistence of infliximab (IV and SC) in France: the Riposte IBD study
Authors: Kirchgesner J , Quiles N , Foulley L , Habauzit C , Benkhalifa S , Prati C
Published: January 2025

Background

Subcutaneous infliximab (IFX-SC) is available in France since 2021. Beyond the pivotal trials, real-life data is needed. The aim of the RIPOSTE study is to evaluate the real-life use of IFX-SC in France at a nationwide level.

Methods

Patients affiliated to the French national health insurance with at least one IFX-SC or intravenous (IV) delivery between February 1, 2021, and December 31, 2022, were included, regardless of therapeutic indication. Three patient groups were defined: patients treated solely with IFX-IV (control group); patients who had received less than 3 infusions of IFX-IV before initiating IFX-SC (initiation group); patients who had received at least 3 infusions of IFX-IV before initiating IFX-SC (switch group). Patients were followed from the first IFX infusion until IFX discontinuation, initiation of another advanced therapy, death, or December 31, 2022. Discontinuation of infliximab was defined by a period of at least 3 months after the last day of estimated exposure without any new treatment delivery. Persistence of IFX-SC was assessed by the Kaplan-Meier method. Concomitant exposure of immunosuppressant (IS) and the occurrence of serious adverse events were also assessed.

Results

A total of 45664 patients received at least one IFX delivery (fig.1), 30842 treated solely with IFX-IV and 12480 patients treated with IFX-SC. Overall, 7467 (59.8%) and 2982 (23.9%) were diagnosed with Crohn’s disease (CD) and ulcerative colitis (UC), including 1449 (19%) and 664 (22%) in the initiation group, respectively. In the initiation group, 129 (8.9%) and 59 patients (9.2%) with CD and UC had not received IFX-IV at induction. The mean age at cohort entry was 40 years (SD, 14.49) in CD and 43 years (SD, 15.73) in UC, with 49% and 53% of men respectively. At 6 months, an IS was associated with IFX-SC in 39% of CD and 34% of UC patients in the initiation group compared to 16% and 17% of CD and UC patients in the switch group. Median patient follow-up for both diseases was 0.92 years, (Q1-Q3; 0.50-1.25). At 6 months, 84% of CD patients (CI [0.82-0.86]) and 80% (CI [0.76-0.83]) of UC patients were still on IFX-SC in the initiation group. Among patients in the switch group, persistence was 90% (CI [0.9-0.91]) for both CD and UC (CI [0.89-0.91]). Switch-back to IFX-IV in patients exposed to IFX-SC during follow-up occurred in 33 CD (2.3%) and 13 UC patients (2.0%) in the initiation group compared to 203 CD (3.4%) and 77 UC patients (3.3%) in the switch group. No new safety signals were identified (Table 1).

Conclusion

Based on a nationwide population-based cohort, over 80% of patients initiating IFX-SC and over 90% in maintenance with IFX-SC remained on treatment at 6 months. These data are consistent with previously published data.
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

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

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

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

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

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

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 < 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) < 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

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

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 > 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

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.
P0628 Patient preferences towards treatment attributes in Inflammatory Bowel Disease: a Brazilian cohort study
Authors: Argollo M , Queiroz N , Kurtz de Mello M , Senra J , Rosa B , Barreto T
Published: January 2025

Background

Inflammatory bowel disease (IBD) is a chronic condition of the gastrointestinal tract characterised by recurring inflammation that usually requires life-long treatment. As the therapeutic landscape is rapidly expanding, there is a growing need to understand patient perceptions of treatment-related attributes. This study explored the preferences for treatment attributes in patients with Crohn’s disease (CD) or ulcerative colitis (UC) in Brazil.

Methods

Adult patients from Argentina, Australia, Brazil, Saudi Arabia and Taiwan who self-reported diagnosis of CD or UC participated in an online survey. In a discrete choice experiment, the relative importance of treatment attributes for CD or UC was estimated using conditional and multinomial logit models.

Results

In Brazil, 200 patients completed survey responses (CD, n = 100; UC, n = 100), with mean patient ages of 34.9±7.9 and 36.1±9.4 years, respectively. Most patients were covered by private insurance, and the majority had been exposed to advanced therapies (74% for CD and 62% for UC). These patients were primarily treated at IBD centers and private hospitals, with a higher percentage reporting general good or fair well-being (82% for CD and 85% for UC). Patients with CD ranked long-term remission on maintenance therapy (34.8%), the rate of 1-year remission (26.2%), and the route of administration (22.3%) as the most important attributes. Patients with UC prioritized corticosteroid-free remission after 1 year (30.3%), the route of administration (30.1%), and the rate of mucosal healing after 1 year (16.2%). Both CD and UC patients considered abdominal pain as the most impactful symptom on their daily lives. General and emotional well-being were rated as the first and second most important aspects for improvement through treatment.

Conclusion

Patient preferences for treatment attributes correlate with CD or UC clinical manifestations and management, highlighting the importance of personalised care and shared decision-making to maximize treatment benefits and provide valuable insights for the stakeholders involved from drug development to treatment access.
P0641 Efficacy of Vedolizumab and Ustekinumab Following Cyclosporine Induction in Acute Severe Ulcerative Colitis: A Retrospective Cohort Study
Authors: Harb M , Bazin T , Solene D , Bresteau C , El Khatib M , Bourdillel J , Colas C , Corcos O , Billiauws L , Joly F , Nuzzo A
Published: January 2025

Background

In corticosteroid-resistant acute severe ulcerative colitis (ASUC), second-line treatment involves infliximab or cyclosporine (CYCLO). With increasing antiTNFα exposed patients, CYCLO is often chosen to prevent emergency colectomy but is limited to the induction phase due to tolerability, serving as a bridge until effective maintenance therapy. In this setting, limited data on vedolizumab (VDZ) and ustekinumab (UST) as maintenance make the choice of an optimal bridge strategy challenging. This study aimed to compare the efficacy of VDZ and UST after CYCLO induction in corticosteroid-resistant ASUC.

Methods

This single-center retrospective cohort included all patients hospitalized for ASUC, responding to CYCLO induction, and starting VDZ or UST maintenance. ASUC was defined by modified Truelove and Witts criteria, with response to CYCLO defined by a Lichtiger score reduction to <10 points for 2 consecutive days, with a minimum 3-point decrease by day 7. The primary outcome was colectomy-free survival; secondary outcomes were treatment persistence and safety.

Results

From 2014-2024, 72 ASUC patients received CYCLO. Fourteen were excluded (non-response, tofacitinib [n=6], infliximab [n=3], and/or emergency colectomy [n=11]), leaving 58 CYCLO-responsive ASUC patients (median age 39, IQR 30-58, 60% female), with 46 on VDZ (79%) and 12 on UST (21%). ASUC was related to ulcerative colitis in 81% (68% pancolitis) and Crohn’s in 19%. Disease duration was 7 years (IQR 2-15), with 91% prior biologic exposure, primarily antiTNF. Presentation included Lichtiger score 10 (IQR 10-12), CRP 40 mg/L (22-79), albumin 29 g/L (27-30), fecal calprotectin 874 µg/g (450-1800), UCEIS 7 (5-8), and Mayo endoscopic score 3 (3-3). Colectomy-free survival was 75% at M12 and 69% at M24 with VDZ and 57% at M12 and M24 with UST (p=0.38, figure 1). Treatment persistence was 48% at M12 and 37% at M24 with VDZ, and 42% at M12 and M24 with UST (p=0.51, figure 2). After adjusting for maintenance therapy, disease type, and severity, colectomy risk factors included albumin <27 g/L (HR=3.4; 95%CI:1.2-9.8) and prior tofacitinib exposure (HR=4.3; 95%CI:1.2-15.8). Over a median 37-month follow-up (95%CI:35-40), 34% of patients experienced adverse events, with 19% severe (mainly CYCLO-related), including 2 deep vein thromboses in the VDZ group and 1 infection in the UST group. No deaths occurred.

Conclusion

In this large cohort of biologic-exposed, corticosteroid-resistant ASUC patients, a CYCLO bridge strategy with VDZ or UST avoided colectomy in two-thirds of patients, with almost 50% treatment persistence at 12 months. There was no significant difference in efficacy, persistence, or safety between strategies.
P0658 Comparison of the Efficacy and Safety of Immunomodulator Use in Geriatric and Non-Geriatric Patients with Inflammatory Bowel Disease
Authors: Arı D , Kenarlı K , Bacaksız F , Arı S , Gökbulut V , Öztürk Ö , Özderin Özin Y , Kalkan İ H
Published: January 2025

Background

The patterns of medication use among elderly inflammatory bowel disease patients vary due to several factors. This study aims to present the outcomes of immunomodulator therapy in both geriatric and non-geriatric patient groups, highlighting differences in treatment effectiveness, reasons for discontinuation, and the incidence of side effects between the two groups.

Methods

A retrospective database was established by reviewing the records of inflammatory bowel disease patients aged 18 and older who received immunomodulator therapy at our clinic over a seven-year period. Patients aged 65 years and above were designated as the geriatric cohort. In addition to demographic and clinical variables, disease activity in ulcerative colitis patients was assessed using the Mayo Disease Activity Index and the Rachmilewitz Endoscopic Activity Index, while the Harvey-Bradshaw Index was employed for Crohn’s disease patients.

Results

The study included 102 patients, comprising 44 with ulcerative colitis and 58 with Crohn’s disease. The median age was 66.5 years (range: 23–87), with 54 patients (52.94%) classified as geriatric (≥65 years). Immunomodulator therapy was discontinued due to side effects in 31 patients (30.39%) and due to remission in 11 patients (10.78%). Additionally, 23 patients (24.21%) showed no response to the treatment. No significant differences were observed between the geriatric and non-geriatric groups regarding the type of inflammatory bowel disease, duration of therapy, concomitant treatments, reasons for discontinuation, side effects, malignancy occurrence, malignancy type, or mortality.

Conclusion

With careful patient selection and close monitoring, immunomodulator therapy in elderly inflammatory bowel diseasepatients can achieve similar effectiveness and risk of side effects as observed in younger patient groups.
P0665 Long-term efficacy and dose intensification of ustekinumab in achieving clinical, laboratory, and endoscopic remission in Crohn’s disease
Authors: Dussias N , Melotti L , Vanigli N , Gionchetti P , Rizzello F
Published: January 2025

Background

Although ustekinumab has been evaluated for Crohn’s disease, long-term effectiveness and the benefits of dose intensification for maintaining clinical and endoscopic remission remain underexplored. Dose intensification strategies may be critical for optimizing outcomes in patients not responding to standard regimens. This study addresses these gaps by analyzing the long-term outcomes of ustekinumab treatment and the impact of dose intensification in a real-world setting.

Methods

This retrospective, observational study was conducted at a tertiary referral center, investigating patients with moderate-to-severe Crohn’s disease treated with ustekinumab. We assessed rates of steroid-free clinical remission, endoscopic remission, and normalization of C-reactive protein (CRP) at baseline, 12, 24, 36, and 48 months post-initiation. Outcomes in patients undergoing dose intensification from every 8 weeks to every 6 or 4 weeks due to incomplete response or loss of efficacy were also evaluated. Clinical remission was defined as Harvey-Bradshaw Index (HBI) ≤4, endoscopic remission as SES-CD ≤2, and CRP normalization as ≤0.5 mg/dL.

Results

A total of 251 patients were included in this study. Of these, 228 continued ustekinumab treatment at 12 months, with 43% achieving steroid-free clinical remission. Clinical remission rates at 24, 36, and 48 months were 47%, 50%, and 40%, respectively. Ileocolonoscopy was performed at 12 months in 115 patients, showing that 31.3% achieved endoscopic remission. This trend continued, with endoscopic remission rates of 30.9% at 24 months, 39.1% at 36 months, and 40% at 48 months. Median C-reactive protein levels dropped from 1.75 mg/dL at baseline to 0.42 mg/dL at 12 months and remained below 0.5 mg/dL at 24, 36, and 48 months (0.37, 0.34, and 0.4 mg/dL, respectively). Over the four-year period, 81 patients underwent dose intensification due to loss of efficacy or insufficient response, with 24.7% achieving clinical remission thereafter. An additional 24.7% achieved a reduction of HBI of at least 3 points after dose intensification, while the remaining 50.6% failed treatment. Adverse events led to treatment discontinuation in 2.4% of patients.

Conclusion

Ustekinumab demonstrated significant efficacy in achieving and maintaining clinical, endoscopic, and laboratory remission over four years in patients with moderate-to-severe Crohn’s disease. Dose intensification led to favorable outcomes in approximately half of the patients, demonstrating that it is a viable option in patients with insufficient response or loss of efficacy with the standard dose.
P0672 Comparative Efficacy of Medical Therapies in Reducing the Risk of Post Operative Recurrence in Crohn’s Disease (PORCD): A Systematic Review and Network Meta-analysis
Authors: Shehab M , Alrashed F , Alrashed O , Alyousefi R , Zoughlami A , Lakatos P L , Siddharth S , Allez M , Miguel R , Bessissow T
Published: January 2025

Background

Up to 50% of patients with Crohn’s disease (CD) will require surgery, and 70-90% experience endoscopic recurrence within the first year postoperatively (1). Despite various treatments, there is scant data on the comparative efficacy to prevent recurrence (2). This study aims to compare the efficacy of medical treatments in preventing PORCD.

Methods

A comprehensive literature review was conducted using Medline, Embase, and the Cochrane Library through October 1, 2024. We included RCTs and prospective cohort studies, excluding pediatric studies, single-arm trials, and dose-comparison studies. The primary endpoint was assessing endoscopic recurrence (ER) (RS ≥i2), and secondary outcome was clinical recurrence (CDAI ≥150, Hanauer’s score ≥2, HBI ≥8) at 6, 12, and ≥18 months postoperatively. Frequentist random-effects network meta-analysis was conducted, reporting OR with 95% CI.

Results

A total of 42 studies were included in this meta-analysis, 38 of which were RCTs, with 2,260 patients with CD. At 6 months, ADA showed the lowest ER (SUCRA= 84.5%), followed by VDZ (74.5%). ADA significantly reduced ER compared to thiopurine (OR = 0.33 [95% CI, 0.12–0.91]), probiotics (OR = 0.17 [95% CI, 0.03–0.99]), and vitamin D (OR = 0.07 [95% CI, 0.01–0.37]). VDZ did not significantly differ from thiopurine, ADA or MDZ. At 12 months, IFX (SURCA= 93%) and ADA (SUCRA= 90%) had the lowest ER, with IFX showing significant reductions compared to thiopurine, MDZ, 5-ASA, ornidazole, and herbals (table1). Similar findings were observed at 18 months, with IFX and ADA maintaining the lowest ER rates. For clinical recurrence, no significant differences were observed among therapies at 6 months. However, at 12 months, ADA and IFX were superior to most therapies, including thiopurine, MTX, and budesonide. By 18 months, ADA had significantly less clinical recurrence than IFX (OR = 0.06 [95% CI, 0.01–0.50]).

Conclusion

Anti-TNFs are more effective than other therapies in preventing post-op CD recurrence. VDZ did not outperform thiopurines. Further RCTs are needed to evaluate newer therapies for post-op CD management.

References

1.Spinelli A, Sacchi M, Fiorino G, Danese S, Montorsi M. Risk of postoperative recurrence and postoperative management of Crohn’s disease. World J Gastroenterol. 2011;17(27):3213-3219. doi:10.3748/wjg.v17.i27.3213

2.Fasulo E, D’Amico F, Osorio L, et al. The Management of Postoperative Recurrence in Crohn’s Disease. J Clin Med. 2023;13(1):119. Published 2023 Dec 25. doi:10.3390/jcm13010119
P0674 Development of a screening tool to address dietary habits in persons with IBD in Germany
Authors: Wilke E L , Wiestler M , Middelhoff M , Schult-Hannemann D , Knoedler L L , Ebert M P , Reindl W , Thomann A K
Published: January 2025

Background

Nutrition plays a crucial role in the development and course of disease in patients with inflammatory bowel disease (IBD). However, standardized nutritional assessments are often lengthy and require the expertise of professional nutritionists, leading to a significant gap in the ability to screen for important dietary factors. As a result, these aspects are frequently overlooked in both clinical practice and scientific research. To address this issue, we aim to develop a short screening instrument that can effectively assess dietary and nutritional aspects in patients with IBD. This tool is not intended to replace, but complement standardized assessments, and to enable clinicians and researchers to address dietary and nutritional aspects in situations where these are otherwise disregarded.

Methods

A comprehensive literature review was conducted to identify nutritional factors with regard to their pro- and antiinflammatory characteristics in the context of IBD. Based on this research, a prototype screening tool was developed in collaboration with nutritional experts from 3 German University Hospitals (Mannheim, Munich, and Hannover). The first phase of validation involved an evaluation of the prototype screener by consecutive outpatients at the University Medical Center Mannheim (UMM) to assess its feasibility and acceptance.

Results

Our screening tool contains 28 questions and asks about the frequency of consumption of certain food groups as well as the type of preparation and eating habits with regard to vegetarian or vegan diet, the frequency of meals and the balance and variety of the diet. In the patient evaluation phase, we received feedback from 52 patients (n=37 female, n=36 with Crohn’s Disease, n=51 with remitted or mild disease (1 moderate, none severe). Mean time to complete the screening tool was 9.3 min (SD 7.8). The vast majority of patients stated that they found the screener somewhat or very important (n=47) and somewhat or very easy to understand (n=48), see fig. 1. Seven patients reported that they found at least one question difficult to understand. Ten patients stated that the screener was missing at least one aspect of their dietary habits. No patients reported any unpleasant questions. A global evaluation of the screener according to the German school grading system (from 1 = very good, 6 = very bad) was rated with a mean grade of 1.6.

Conclusion

This newly developed screening tool to semi-quantitatively assess dietary habits and relevant nutritional aspects in IBD was well-accepted and positively evaluated by patients. In the next step, we will adapt the questionnaire according to patient feedback and then initiate the next phase of the validation process in a multicentric setting.
P0676 Inborn Errors of Immunity Associated with Inflammatory Bowel Disease at a Tertiary Care Centre
Authors: Albadawi N , Almuhaya H , Alrossais N , Binzuman G , Alhaddab N , Aljefri N , Alsehaim K , Alshaikh A , Alsoqair S , Arnaout R , Alshareef S , Albawardy B , Alsohaibani F
Published: January 2025

Background

Inborn errors of immunity (IEI) are genetic disorders causing immune dysregulation, often increasing susceptibility to infections, autoimmunity, and inflammation. IEI-associated inflammatory bowel disease (IBD) can mimic classic IBD, which includes ulcerative colitis (UC) and Crohn’s disease (CD). Treatment for IEI-associated IBD is not well-established. This study aims to assess the prevalence, clinical and endoscopic presentation, and treatment outcomes of IBD in IEI patients.

Methods

This is a single center, retrospective study. All patients were ≥ 14-years of age with a confirmed diagnosis of IEI and IBD based on clinical, endoscopic, and histologic evaluations. Primary outcomes included the prevalence, clinical and endoscopic characteristics. The secondary outcomes included IBD treatment response and safety.

Results

Among 390 patients with IEI 36 (18.7%) exhibited gastrointestinal symptoms, with diarrhea being the most prevalent symptom (69.3%, n=25). In the 19 patients who underwent colonoscopy, abnormalities were observed in 9 (47.4%) with ulcerations being the most common finding (33.3%). The prevalence of IEI-associated IBD was 2.3%(n=9), with the most prevalent being CD (55.5%, n=5), followed by UC and IBD-unclassified(22.2%, n=2). Family history of IEI was noted in (55.5%, n=5), while only (11.1%, n=1) had family history of IBD. Chronic diarrhea (88.9%) was the most common clinical presentations. Initial fecal calprotectin levels were >250 in all patients. Colonoscopy was performed on 8 patients (89%), of those (66.7%, n=6) had abnormal finding. Radiological abnormalities such as strictures, fistulas, perianal disease, and abscesses were noted in (55.5%, n=5). Medical treatment included corticosteroids33.3% (n=3), immunosuppressants in 22% (n=2) , biologics including (vedolizumab, Infliximab and Adalimumab) in 33.3% (n=3) and 1 patient received no IBD specific treatment. Clinical response was noted in 3 patients (1 on corticosteroids and 2 on immunosuppressants), with no improvement in those who received biologics. Surgery related to IBD was required in 22.2% (n=2). One patient had cytomegalovirus (CMV) colitis and four developed bacterial infections (none were on biologics). The mortality rate among the IEI-IBD cohort was 44.4%, with no significant associations between mortality and factors such as sex, IBD subtype, history of bacterial GI infections, extra-GI autoimmune disease, prior IBD surgery or age at IBD and IEI diagnosis (Table 1).

Conclusion

The prevalence of IEI-IBD was low but it is associated with a high mortality rate. Chronic diarrhea is the most common presentation and medical therapy success was limited, with improvement in only one-third of patient. Further research of larger cohorts is needed.