BACKGROUND Low drug concentrations have been linked to antidrug antibody (ADA) formation. High clearance is a major reason for low drug levels leading to treatment failure in patients with inflammatory bowel disease (IBD) receiving infliximab (IFX).AIM To explore the predictive value of initial IFX clearance on outcomes and assess the impact of Bayesian model (iDose)-guided IFX dosing on clearance and outcomes during induction and early maintenance treatment.METHODS Data from a Phase 3 study of 220 CT-P13/originator IFX-treated patients with Crohn's disease were used to develop probability models for outcomes including mucosal healing (MHEAL), biomarker response [C-reactive protein (CRP)], ADA development, a composite endpoint and time to first ADA formation, based on initial clearance. Subsequently, patients with characteristics suggesting rapid initial clearance were enrolled in a <= 120-day (October 2018 to December 2019) compassionate use program of iDose-guided IFX treatment as a proof of concept to determine if the probabilities from initial clearance could be improved with individualized therapy. Serial serum IFX concentrations, clearance, outcome probabilities, and treatment outcomes were analyzed.RESULTS In the CT-P13 study, population pharmacokinetic was consistent with previously published models. Initial clearance was a significant predictor of several outcomes including MHEAL, CRP normalization, a composite endpoint ((1) CDAI at week 54 was at least 150 points less than baseline; (2) MHEAL at week 54; (3) CRP was in normal range at week 54; and (4) FCP was less than 250 at week 54) and ADA formation. In the proof-of-concept study, 10 patients received iDose-guided IFX treatment. Initial clearance ranged from 0.017 L/day to 1.11 L/day, prompting up to three IFX infusions within the first 2 weeks. Two patients were discontinued due to ADA. Generally, clearance slowed over time and inflammatory biomarker levels improved. There were no adverse effects.CONCLUSION Initial IFX clearance correlates with efficacy metrics and ADA formation. These probability curves may be useful to identify patients at risk of treatment failure or ADA who may benefit from individualized therapy. iDose-guided treatment successfully achieved targeted serum IFX concentrations, reducing risk of ADA formation. Proactive therapeutic drug monitoring and targeted dosing based on early IFX clearance may improve treatment outcomes for patients with IBD.

Background:Eosinophilic esophagitis (EoE) is a chronic, type-2 inflammation-driven disease causing dysphagia. Although patients with other type-2 inflammatory diseases (type-2 ID) or inflammatory bowel disease (IBD) may have an increased risk of EoE, there is limited information about the prevalence of EoE in these specific populations. Objectives:This study aims to assess the prevalence of clinically relevant dysphagia as well as underlying EoE in patients with type-2 ID or IBD. Design:This is a cross-sectional, multicenter study of patients with type-2 ID (asthma, rhinosinusitis with polyposis nasi, allergic rhinitis, atopic dermatitis, Immunoglobulin E (IgE)-mediated food allergies) or IBD from the Medical University of Vienna and Floridsdorf Allergy Center. Methods:Patients were screened for esophageal dysphagia using the Brief Esophageal Dysphagia Questionnaire (BEDQ). Relevant dysphagia was defined as a BEDQ score ⩾4, or having a history of bolus impaction or emergency department visit due to dysphagia within the past year. Endoscopy with esophageal biopsies was offered to all patients with relevant dysphagia to screen for EoE. Results:A total of 687 patients (45.9% female, median age 45 years, 53.9% with IBD, 48.5% with a type 2 ID) were screened. Overall, 8.9% (n = 61) reported relevant dysphagia. Endoscopy with biopsies was performed in 22 patients, and 18 patients had undergone endoscopy the year prior to the study. In total, 6 newly diagnosed cases of EoE were observed, while 7 patients had a known history of EoE, resulting in an overall prevalence of 13 patients (1.9%). Patients with any type-2 ID had numerically more EoE (2.7%) than patients with IBD (1.9%). Conclusion:While the prevalence of dysphagia among patients with type-2 ID and IBD may not exceed that of the general population, the prevalence of EoE in these populations may be higher than previously recognized.

BACKGROUND:Despite an increasing number of biological therapies, publications report conflicting surgery rates in Crohn's disease (CD). AIMS:To examine trends in the rates of surgeries for intestinal and perianal fistulizing CD in the era of biologics in Austria. METHODS:In this nationwide population-based study patients with a diagnosis of CD and CD-related intestinal or perianal surgeries between 2011 and 2019 were included. Data were retrospectively retrieved from the Austrian Health Insurance Funds. Absolute numbers of CD-related surgeries per year and per 100,000 Austrians were calculated and changes during the observation period compared with estimates of the CD prevalence. RESULTS:A cohort of 6,593 patients with CD underwent a total of 4,758 intestinal and 4,794 perianal surgeries from 2011 through 2019. Intestinal surgery rates remained stable with 5.9 vs. 6.0/100,000 Austrians and perianal surgeries rose from 5.0 to 7.5/100,000, equalling an annual increase of 0.2% and 5.2%, respectively, whereas the prevalence of CD rose by 3.2% annually (95% confidence interval 1.9 - 4.6). CONCLUSION:In Austrian CD patients intestinal resection rates remained stable, whereas perianal fistula surgeries increased. Adjustment for rising CD prevalence revealed fewer intestinal resections per CD patient years, while perianal fistula surgery rates continued to increase.

Background:The cumulative probability of patients with Crohn's disease (CD) requiring a stoma at a tertiary center is unknown. We sought to evaluate the time to stoma formation after diagnosis as well as risk factors for stoma formation in CD patients. Methods:This is a retrospective, longitudinal cohort study on consecutive patients with CD at an Austrian tertiary referral university center. In brief, patients with CD were identified and disease-specific data were captured prior to June 2023. The probability of stoma-free survival by subgroups of various potential risk factors was assessed by means of Kaplan-Meier estimates (Log-rank test). Results:Of 1267 CD patients, 142 (11.2%) underwent a stoma formation (80 ileostomies, 62 colostomies), of which 51 (35.9%) were permanent stomas. The probability of stoma-free survival at 10 and 20 years after diagnosis was 92% and 86%, respectively. Ileocolonic and colonic location, penetrating behavior, and perianal disease were associated with a higher risk for stoma formation (each P < .001). If these risk factors coincided, the probability of stoma-free survival at 10 and 20 years after diagnosis was only 76.4% and 67.2%, respectively. Patients diagnosed from 2000 onward had a trend for a lower stoma risk than patients diagnosed earlier (P = .084). Conclusions:The coincidence of colonic or ileocolonic involvement, penetrating behavior, and perianal fistulas significantly reduced the probability of stoma-free survival to 68% 20 years after diagnosis. Identification of these risk factors for stoma formation may help identify patients at risk and thus raise awareness for this group.

Abstract Microbial dysbiosis is a hallmark of inflammatory bowel diseases (IBD); however, its drivers and impact on disease pathophysiology are poorly understood. Applying neural network-based feature attribution to metabolomics and metagenomics datasets from >5000 individuals, we identified epimerized host derived bile acids (BAs) produced by microbial hydroxysteroid dehydrogenases (HSDHs) as a novel hallmark of IBD-associated dysbiosis. Epimerized BAs reduce FXR activity in intestinal epithelial cells and dampen their production of FGF19, a negative feedback regulator of host-derived bile acid (HBA) production in the liver. Increased HBA levels drive colonic epithelial remodeling by impacting goblet cell maturation and select for HSDH-carrying bacteria that transform bactericidal HBA into less toxic, epimerized forms. Confirming the translational relevance of these findings, we demonstrated that high HBA levels limit fecal microbiota transplant engraftment and show that BA sequestering drugs support microbiome recovery in patients with high HBA levels. Together, we discover that elevated HBAs deplete BA-sensitive commensals and favor the growth of HSDH-encoding pathobionts that disrupt host BA feedback signaling, establishing a causal link between changes in microbial ecology and IBD pathophysiology.

BACKGROUND:Low drug concentrations have been linked to antidrug antibody (ADA) formation. High clearance is a major reason for low drug levels leading to treatment failure in patients with inflammatory bowel disease (IBD) receiving infliximab (IFX). AIM:To explore the predictive value of initial IFX clearance on outcomes and assess the impact of Bayesian model (iDose)-guided IFX dosing on clearance and outcomes during induction and early maintenance treatment. METHODS:Data from a Phase 3 study of 220 CT-P13/originator IFX-treated patients with Crohn's disease were used to develop probability models for outcomes including mucosal healing (MHEAL), biomarker response [C-reactive protein (CRP)], ADA development, a composite endpoint and time to first ADA formation, based on initial clearance. Subsequently, patients with characteristics suggesting rapid initial clearance were enrolled in a ≤ 120-day (October 2018 to December 2019) compassionate use program of iDose-guided IFX treatment as a proof of concept to determine if the probabilities from initial clearance could be improved with individualized therapy. Serial serum IFX concentrations, clearance, outcome probabilities, and treatment outcomes were analyzed. RESULTS:In the CT-P13 study, population pharmacokinetic was consistent with previously published models. Initial clearance was a significant predictor of several outcomes including MHEAL, CRP normalization, a composite endpoint ((1) CDAI at week 54 was at least 150 points less than baseline; (2) MHEAL at week 54; (3) CRP was in normal range at week 54; and (4) FCP was less than 250 at week 54) and ADA formation. In the proof-of-concept study, 10 patients received iDose-guided IFX treatment. Initial clearance ranged from 0.017 L/day to 1.11 L/day, prompting up to three IFX infusions within the first 2 weeks. Two patients were discontinued due to ADA. Generally, clearance slowed over time and inflammatory biomarker levels improved. There were no adverse effects. CONCLUSION:Initial IFX clearance correlates with efficacy metrics and ADA formation. These probability curves may be useful to identify patients at risk of treatment failure or ADA who may benefit from individualized therapy. iDose-guided treatment successfully achieved targeted serum IFX concentrations, reducing risk of ADA formation. Proactive therapeutic drug monitoring and targeted dosing based on early IFX clearance may improve treatment outcomes for patients with IBD.

Results on exposure-efficacy relationships for vedolizumab in patients with Crohn's disease are contentious. Our study aimed at exploring the relationship between vedolizumab serum concentrations measured during induction and maintenance and treatment outcomes in Crohn's disease patients in a real-world setting.Crohn's disease patients treated with vedolizumab between January 2014 and July 2022 at our tertiary care centre were included. Serum vedolizumab concentrations were measured on at least one of the following time points: week 2, 6, 12, 26, and/or 52. Treatment efficacy was evaluated at weeks 12, 26 and 52 as clinical remission based on patients reported outcomes, faecal calprotectin and C-reactive protein remission.In total, 58 patients (55.2% females) were included. At baseline, active disease, defined either by increased faecal calprotectin, C-reactive protein or patients reported outcomes, was observed in 53 patients (91.4%). Week 12 vedolizumab serum levels were higher in clinical remitters versus non-remitters at weeks 12 and 52 (p <0.05). However, in adjusted multivariate analyses no association between vedolizumab levels and therapy outcomes was observed.In our retrospective study, vedolizumab serum concentrations measured during induction treatment were not associated with clinical and feacal calprotecin remission at weeks 12, 26 and 52.

Abstract Background Bowel urgency is one of the most bothersome symptoms in patients with Ulcerative colitis (UC) and Crohn´s disease (CD). However, only recently attention has been focused on this symptom and data on associated factors, especially in patients with CD, is scarce. The Health Outcome Observatory (H2O) project aims to standardize and facilitate the collection of patients reported outcomes (PROs) and clinical outcomes by developing multi-stakeholder agreed Core Outcome Sets (COS) including one for patients with inflammatory bowel disease (IBD). The present study describes preliminary data on bowel urgency. Methods We analyzed prospectively collected data from the Health Outcome Observatory (H2O) project at the Medical University of Vienna, Austria. Bowel urgency was one of the collected variables and was defined by the validated Urgency Numeric Rating Scale (NRS) ≥ 3 (on a 0-10 scale). We used linear regression with bowel urgency as the outcome and age, gender, diagnosis (CD/IBDU/UC) and quality of life (PROMIS_Global_10_02; scale from 1-5) as predictors. Results Out of a total of 480 included patients who took part in the H2O project, we analyzed 388 patients who answered the question regarding bowel urgency. The mean urgency NRS in CD patients was 2.71 (SD +/- 2.92) and 2.24 in UC (SD +/- 2.68). Numerically more patients with CD (40.9%) than with UC (33.8%) complained about bowel urgency. Quality of life (coef 1.30, coef (95% CI) 1.01-1.59, p<0.01) was associated with bowel urgency. Age, gender, diagnosis (CD vs UC vs IBDU) was not associated with bowel urgency (see Table 1). Conclusion Bowel urgency is a common symptom in patients with inflammatory bowel disease and is associated with a lower quality of life. Caregivers should acknowledge the importance of this debilitating symptom. References Fierens L, Carney N, Novacek G, van der Woude CJ, Siegmund B, CasellasF, Borruel N, Huberts AS, Sonnenberg E, Gerold N, Primas C, Hedin CRH,Stamm T, Julsgaard M, Fiorino G, Radice S, Zini MLL, Gross E, Sander C,Arijs I, Vakouftsi VR, Koltai T, Health Outcomes Observatory H O PatientAdvisory Board For Inflammatory Bowel Diseases, Health OutcomesObservatory H2O Steering Committee, Charlafti I, Ferrante M. A CoreOutcome Set for Inflammatory Bowel Diseases: Development andRecommendations for Implementation in Clinical Practice Through anInternational Multi-stakeholder Consensus Process. J Crohns Colitis.2024 Oct 15;18(10):1583-1595. doi: 10.1093/ecco-jcc/jjad195. PMID:38019894.

Eosinophilic esophagitis (EoE) is one of the main causes of esophageal food impaction (EFI). Since only few endoscopists take biopsies during the emergency endoscopy at EFI presentation, as is recommended by current guidelines, a high number of patients will not have a proper diagnosis after EFI. Hence, we investigated the change of biopsy rates and the etiology of EFI over 11 years. All patients presenting at the emergency department (ED) of a tertiary center with an EFI who underwent esophagogastroduodenoscopy (EGD) between 2013 and 2023 were included. Clinical and endoscopic variables were analyzed retrospectively. We performed a binary logistic regression model to predict biopsy performance. A total of 180 EFI cases (67

Abstract Background The Health Outcome Observatory (H2O) project aims to standardize and facilitate the collection of patient reported outcomes (PROs) and clinical outcomes by Core Outcome Sets (COS) in patients with inflammatory bowel disease (IBD).1 The present study describes preliminary data on clinical and biomarker remission as well as quality of life. Methods This is a real-world interim analysis of IBD patients included in the H2O project at the Medical University of Vienna, Austria, and the Hospital Universitari Vall d’Hebron, Barcelona, Spain. The variables analyzed were part of the COS. Clinical remission was defined by PRO-2 (for Crohn’s disease (CD): number of liquid or very soft stools ≤3, abdominal pain score ≤1; for ulcerative colitis (UC): rectal bleeding score=0, stool frequency score ≤1), biomarker remission by faecal calprotectin (<150g/g) and C-reactive protein (<0.5mg/dl), and quality of life by PROMIS_10_Q02 (quality of life answered as very good or excellent). Co-primary endpoints were clinical and biomarker remission and a very good or excellent quality of life. A descriptive analysis was performed. Results 532 patients were included in Austria (221 female [42%]; 298 CD, 178 UC, 6 IBDU, 50 with missing diagnosis) and 30 in Spain (14 female [47%]; 18 CD, 12 UC). 138 of 532 patients in Austria (26%) did not provide PRO data. The majority of patients were on advanced therapies (CD: 221/298; 77%; UC: 118/178; 66%). Among CD patients 175 were in PRO-2 remission in Austria (80%) and 13 in Spain (72%), the corresponding numbers of patients in UC PRO-2 remission were 86 in Austria (62%) and 11 in Spain (92%). Biomarker remission was observed in 128/240 CD patients (53%) and 84/135 UC patients (62%). Detailed results of the PRO-2 and of the biomarker values of the Austrian IBD patients are given in Table 1. Very good or excellent quality of life was reported by 97/224 (43.3%) CD patients and 69/140 (49.2%) UC patients. 77/240 CD patients (32%) and 58/135 UC patients (43%) were in clinical PRO-2 as well as biomarker remission and had a very good or excellent quality or life. Conclusion While a large number of IBD patients in tertiary university centers were in clinical PRO-2 remission a lower number of patients had a very good or excellent quality of life. Biomarker remission was achieved almost equally often as clinical PRO-2 remission in UC patients but less often in CD patients. About one third of the patients were in clinical PRO-2 and biomarker remission and had a very good or excellent quality of life. Despite the frequent use of advanced therapies there is a need for treatment optimizing to reach all treatment goals. References 1.Fierens L, Carney N, Novacek G, van der Woude CJ, Siegmund B, Casellas F, Borruel N, Huberts AS, Sonnenberg E, Gerold N, Primas C, Hedin CRH, Stamm T, Julsgaard M, Fiorino G, Radice S, Zini MLL, Gross E, Sander C, Arijs I, Vakouftsi VR, Koltai T, Health Outcomes Observatory H O Patient Advisory Board For Inflammatory Bowel Diseases, Health Outcomes Observatory H2O Steering Committee, Charlafti I, Ferrante M. A Core Outcome Set for Inflammatory Bowel Diseases: Development and Recommendations for Implementation in Clinical Practice Through an International Multi-stakeholder Consensus Process. J Crohns Colitis. 2024 Oct 15;18(10):1583-1595. doi: 10.1093/ecco-jcc/jjad195. PMID: 38019894.

Abstract Background Smoking is the best-known environmental risk factor for poor outcome of Crohn’s disease (CD). Since smoking cessation improves the prognosis of CD, patients are encouraged to quit smoking. This study aimed to assess the smoking behaviour among CD patients and explore changes after diagnosis of CD. Methods This is a retrospective single tertiary center cohort study of 1267 patients with CD with a median follow-up of 16.8 years (IQR - 18.3) whose characteristics are recorded via a validated data software (IBDIS, Inflammatory Bowel Disease Information System). Smoking behaviour was categorized into never smokers, current smokers, and ex-smokers (those who quit smoking at any point). The primary objective was smoking cessation during follow-up. The probability of smoking was calculated for those CD patients who smoked at the time of diagnosis of CD by means of Kaplan-Meier estimates. Statistical analyses were conducted using R software, employing log-rank tests for estimating differences with a significance level of alpha = 0.05. Results In total 1,128 CD patients with a complete data set were analysed (Table 1). 161 (14.2%) patients started and stopped smoking prior to diagnosis of CD. At the time of diagnosis, 541 patients (47.9%) were smokers, and 239 (44.2%) of them quit smoking during follow up. The median time from CD diagnosis to cessation for the 239 patients who were smokers at the time of diagnosis and subsequently quit was 8.6 years (IQR - 10.6 years). 80 patients (7%) started smoking after diagnosis, with 50 of these patients quitting thereafter. The probability of smoking in those CD patients who smoked at the time of diagnosis decreased over time to 0.96 (95% CI 0.95-0.98) at 1yr, 0.85 (95% CI 0.83-0.89) at 5 yrs, 0.71 (95% CI 0.67-0.76) at 10 yrs, and 0.52 (95% CI 0.47-0.57) at 20 yrs after diagnosis for the entire cohort with no significant difference between genders (p=0.76) (Figure 1a). Patients who were diagnosed 2010 and later (n=182) were more likely to stop smoking than patients diagnosed before 2010 (n=359) (p<0.001) (Figure 1b). However, the probability to smoke 10 years after the diagnosis was still high in both groups (0.62 (95% CI 0.52-0.74) and 0.75 (95% CI 0.71-0.79), respectively). Conclusion A substantial proportion of CD patients smoked at the time of diagnosis. 20 years after diagnosis around half of the patients still continued to smoke. Improved smoking cessation programs are needed to reduce the impact of smoking on the course of the disease.

Background Corticosteroids are used for induction of remission in patients with moderately to severely active ulcerative colitis. However, up to one-third of patients fail to this therapy. We investigated if fecal microbial composition or its metabolic capacity are associated with response to systemic corticosteroids. Methods In this prospective, multicenter study, patients with active ulcerative colitis (Lichtiger score ≥4) receiving systemic corticosteroids were eligible. Data were assessed and fecal samples collected before and after 4 weeks of treatment. Patients were divided into responders (decrease of Lichtiger Score ≥50%) and nonresponders. The fecal microbiome was assessed by the 16S rRNA gene marker and analyzed with QIIME 2. Microbial metabolic pathways were predicted using parsimonious flux balance analysis. Results Among 93 included patients, 69 (74%) patients responded to corticosteroids after 4 weeks. At baseline, responders could not be distinguished from nonresponders by microbial diversity and composition, except for a subgroup of biologic-naïve patients. Within 4 weeks of treatment, responders experienced changes in beta diversity with enrichment of ascribed beneficial taxa, including Blautia, Anaerostipes, and Bifidobacterium, as well as an increase in predicted butyrate synthesis. Nonresponders had only minor longitudinal taxonomic changes with a significant increase of Streptococcus salivarius and a microbial composition shifting away from responders. Conclusion Baseline microbial diversity and composition seem to be of limited use to predict response to systemic corticosteroids in active ulcerative colitis. Response is longitudinally associated with restoration of microbial composition and its metabolic capacity.

Abstract Background Patients suffering from ulcerative colitis (UC) have reduced life qualities and an increased risk of developing cancer. Current treatment options are limited and have a ceiling effect with remission rates of ~35%. A possible reason is the multi-factorial aetiology, which are associated with an overactivation of the immune system and a dysbiosis of the gut microbiome. An important step towards a better understanding is the characterization of epithelial lesions. Their severity is classified by the Mayo score system based on their macroscopic appearance. While previous studies analysed cellular changes within the colon in UC patients, a detailed characterization of different UC-associated lesions are still missing, which is the aim of our study in collaboration with Sanofi Pharmaceuticals. Methods We recruit patients with active disease at our endoscopy unit and collect different biopsies from multiple regions within these patients to compare the reproducibility of single cell RNA sequencing (scRNAseq) results of similar appearing lesions within and between patients. For the sample preparation, we include a cellular enrichment step for immune, epithelial and stromal cells before performing 10x scRNAseq to obtain equal numbers for each cell fraction from every sampled area. Results Our cellular isolation strategy allows successful recovery of fibroblast, epithelial and immune cell fractions from each lesion. All expected epithelial cell types as previously described are detected in our dataset as well. Moreover, our experimental setup to obtain comparable numbers of fibroblasts, epithelial and immune cells enables us now to investigate cell-cell communication differences within different Mayo score lesions. For example, CXCL signal increased with the severity of macroscopic lesions and involves multiple cell types. Conclusion Our preliminary results promise exciting insights into cell-cell communications at an unprecedented depth, which identifies aberrant signalling pathway that may contribute to treatment failure in the clinics.

Abstract Background Background: Vedolizumab (VDZ), an α47-integrin inhibitor, is approved for the treatment of moderate to severe Crohn’s disease (CD). Exposure-response relationship for VDZ is less evident in CD. Here, we are exploring associations between serum VDZ serum concentrations and clinical/biomarker-defined endpoints from a single center, real-world cohort. Methods Methods: Electronic health data records of CD patients during their first year of treatment with VDZ from January 2014 – July 2022 at our tertiary care center were obtained. Serum drug levels (TDL) and their correlation with outcomes were assessed at specified timepoints – weeks 12 (± 2), 26 (± 4) and 52 (± 6). Clinical remission was assessed by patient reported outcomes as suggested in STRIDE II guidelines (stool frequency ≤ 3 and abdominal pain ≤ 1). Fecal calprotectin (fCP) values ≤ 150 µg/g marked biomarker remission. Vedolizumab drug levels were measured with IDKmonitor Vedolizumab drug level ELISA kit (Immundiagnostik AG, Germany), In case of missing data patients were categorized as non-responders. For association modelling, multivariable fractional polynomials and generalised additive models were used (R statistical software, v4.1.2; R Core Team). Results Results: In total, 58 patients (females = 55.2%) with at least two available data points were included (Table 1). Sixteen individuals (16/58, 27.6%) were naive for biologics therapies. 98.3% (57/58) reached week 12 (± 2). Both at weeks 26 and 52 91.4% (53/58) subjects still were on drug. Clinical remission was achieved in 51.7% (30/58), 49.1% (26/53) and 45.2% (24/53) cases at weeks 12, 26 and 52, respectively, with biomarker remission rates of 24.1% (14/58), 35.8% (19/53) and 27.6% (16/53) patients reached biomarker remission. TDLs differed only between clinical remitters and non-remitters at week 26 (Mann-Whitney-U-test, p = 0.04). Also, there was no significant association between clinical and biomarker remission at defined timepoints and corresponding TDLs (for all p > 0.05). TDLs at week 2 and 6 were correlated with fCP values at the same time (rho: -0.327, p = 0.03 at week 2 and rho: -0.356, p = 0.02 at week 6). When TDLs at week 2 and week 6 were taken into consideration and associated separately with therapy outcomes in a univariate regression, only association between serum levels at week 6 and biomarker remission at weeks 26 and 52 was found (p = 0.02 and p = 0.03, respectively). Conclusion Conclusion: The only association between serum drug levels and remission was found between TDLs at week 6 and biomarker remission at weeks 26 and 52 suggesting a complex exposure-response relation for vedolizumab in CD patients.

ObjectiveIntravenous iron—a common treatment for anaemia and iron deficiency due to inflammatory bowel disease (IBD)—can cause hypophosphataemia. This trial compared the incidence of hypophosphataemia after treatment with ferric carboxymaltose (FCM) or ferric derisomaltose (FDI).DesignThis randomised, double-blind, clinical trial was conducted at 20 outpatient hospital clinics in Europe (Austria, Denmark, Germany, Sweden, UK). Adults with IBD and iron deficiency anaemia (IDA) were randomised 1:1 to receive FCM or FDI at baseline and at Day 35 using identical haemoglobin- and weight-based dosing regimens. The primary outcome was the incidence of hypophosphataemia (serum phosphate <2.0 mg/dL) at any time from baseline to Day 35 in the safety analysis set (all patients who received ≥1 dose of study drug). Markers of mineral and bone homeostasis, and patient-reported fatigue scores, were measured.ResultsA total of 156 patients were screened; 97 (49 FDI, 48 FCM) were included and treated. Incident hypophosphataemia occurred in 8.3% (4/48) FDI-treated patients and in 51.0% (25/49) FCM-treated patients (adjusted risk difference: −42.8% (95% CI –57.1% to –24.6%) p<0.0001). Both iron formulations corrected IDA. Patient-reported fatigue scores improved in both groups, but more slowly and to a lesser extent with FCM than FDI; slower improvement in fatigue was associated with greater decrease in phosphate concentration.ConclusionDespite comparably effective treatment of IDA, FCM caused a significantly higher rate of hypophosphataemia than FDI. Further studies are needed to address the longer-term clinical consequences of hypophosphataemia and to investigate mechanisms underpinning the differential effects of FCM and FDI on patient-reported fatigue.

Background: Among patients with ulcerative colitis, 30–50% receive corticosteroids within the first five years after diagnosis. We aimed to reconsider their effectiveness in the context of the biologic era. Methods: In this prospective, multicenter study, patients with active ulcerative colitis (Lichtiger score ≥ 4) were eligible if initiating systemic corticosteroids. The primary endpoint was clinical response (decrease in the Lichtiger score of ≥50%) at week 4. Secondary endpoints included combined response defined as clinical response and any reduction in elevated biomarkers (CRP and/or calprotectin). Steroid dependence was assessed after three months. Results: A total of 103 patients were included. Clinical response was achieved by 73% of patients, and combined response by 68%. A total of 15% of patients were steroid-dependent. Activity of colitis did not influence short-term response to treatment but increased the risk for steroid dependence. Biologic-naïve patients responded better than biologic-experienced patients. Past smoking history (OR 5.38 [1.71, 20.1], p = 0.003), hemoglobin levels (OR 0.76 [0.57, 0.99] for higher levels, p = 0.045), and biologic experience (OR 3.30 [1.08, 10.6], p = 0.036) were independently associated with nonresponse. Conclusion: Disease activity was not associated with short-term response to systemic corticosteroids but was associated with steroid dependence in patients with active ulcerative colitis. Exposure to biologics negatively affects response rates.

Background and Aims Standardising health outcome measurements supports delivery of care and enables data-driven learning systems and secondary data use for research. As part of the Health Outcomes Observatory [H2O] initiative, and building on existing knowledge, a core outcome set [COS] for inflammatory bowel diseases [IBD] was defined through an international modified Delphi method.Methods Stakeholders rated 90 variables on a 9-point importance scale twice, allowing score modification based on feedback displayed per stakeholder group. Two consecutive consensus meetings were held to discuss results and formulate recommendations for measurement in clinical practice. Variables scoring 7 or higher by >= 80% of the participants, or based on consensus meeting agreement, were included in the final set.Results In total, 136 stakeholders (45 IBD patients [advocates], 74 health care professionals/researchers, 13 industry representatives, and four regulators) from 20 different countries participated. The final set includes 18 case-mix variables, three biomarkers [haemoglobin to detect anaemia, C-reactive protein and faecal calprotectin to detect inflammation] for completeness, and 28 outcomes (including 16 patient-reported outcomes [PROs] and one patient-reported experience). The PRO-2 and IBD-Control questionnaires were recommended to collect disease-specific PROs at every contact with an IBD practitioner, and the Subjective Health Experience model questionnaire, PROMIS Global Health and Self-Efficacy short form, to collect generic PROs annually.Conclusions A COS for IBD, including a recommendation for use in clinical practice, was defined. Implementation of this set will start in Vienna, Berlin, Barcelona, Leuven, and Rotterdam, empowering patients to better manage their care. Additional centres will follow worldwide.