BACKGROUND:Real-world evidence is needed to understand the comparative effectiveness of biologics in Crohn's disease (CD) under routine-care conditions. We conducted a pooled analysis of individual patient data from prospective German CD registries (BioCrohn, RUN-CD, VEDO-IBD) in the UMBRELLA-IBD data warehouse. METHODS:We included 1567 adults with CD who initiated anti-TNF therapy (adalimumab or infliximab), ustekinumab or vedolizumab. The main outcome was clinical remission (CR) at 24 months (HBI ≤ 4). Additional outcomes included HBI, EQ-VAS and treatment persistence over time. Between-group comparisons used propensity-score-based inverse probability of treatment weighting. RESULTS:After weighting, CR following induction was observed in a slightly higher proportion of patients initiating anti-TNF therapy (74.5%) than ustekinumab (69.4%) or vedolizumab (65.3%) (p = 0.035). Clinical response was 77.9%, 73.5% and 67.8%, respectively (p = 0.015). At 24 months, CR rates were similar in magnitude (anti-TNF, 53.4%; ustekinumab, 63.5%; vedolizumab, 58.7%) but were higher with ustekinumab than anti-TNF (p = 0.004). Over 24 months, treatment persistence differed (log-rank p < 0.001) and was highest for adalimumab (81.4%), lowest for infliximab (66.6%), and intermediate for ustekinumab (78.6%) and vedolizumab (76.9%). HBI decreased and remained low, and EQ-VAS improved, with no relevant between-group differences. CONCLUSION:Overall effectiveness in CD was high, with only small differences between biologic therapies. At the end of induction, CR was slightly higher with anti-TNF therapy than with vedolizumab, whereas at 24 months it was slightly higher with ustekinumab than with anti-TNF. Marked differences in treatment persistence among the evaluated biologics suggest that persistence as an endpoint is not fully explained by CR alone.

INTRODUCTION:European and National Celiac Disease (CeD) guidelines offer an easy pathway to diagnose CeD. The German CeD Registry aimed to assess symptoms and clinical findings before diagnosis, diagnostic delay, care during the diagnostic process, and factors associated with persistence of symptoms. METHODS:Individuals with CeD provided demographic, clinical, and healthcare-related information. Participants were divided into four subgroups according to age at diagnosis (>18 or <18 years) and year of diagnosis (before and since 2012). Factors associated with symptoms after at least 1 year on a gluten-free diet (GFD) were assessed using multivariate logistic regression. RESULTS:From 11/2019 to 10/2021, 2,333 participants were enrolled. After exclusion of 169 (7.2%), 2,164 remained for analysis, thereof 796 (36.8%) were diagnosed <18 years, and 1,283 (59.3%) since 2012. Most common symptoms before diagnosis included abdominal pain (83%), bloating (82%), fatigue (78%), and diarrhoea (71%). Diagnostic delay after 2012 was longer in adults than children (median 4.4 years [interquartile range; IQR: 1.2-13.0] versus 1.1 [IQR: 0.5-2.2], respectively) (p < 0.001). Guideline-conform diagnoses increased over time. After diagnosis, only 60% received professional dietary counselling. Factors associated with symptoms despite GFD included female gender (odds ratio [OR]: 1.79 [95% confidence interval: 1.34; 2.40], p < 0.001), same symptom before diagnosis (OR: 3.45 [2.45; 4.96], p < 0.001), insufficient information provided at diagnosis (OR: 1.25 [1.00; 1.57], p = 0.046), and age at diagnosis (per decade) (OR: 1.11 [1.04; 1.18], p < 0.001) but not time since diagnosis. CONCLUSIONS:Our findings revealed deficits in awareness, the diagnostic process, and post-diagnostic care that are linked to decreased clinical improvement over time.

The Competence Network Inflammatory Bowel Diseases (Kompetenznetz Darmerkrankungen) was established in Germany in 1999 through a 10-year funding programme by the German Ministry of Education and Research. It was created to address the growing gap between the rising prevalence and therapeutic complexity of inflammatory bowel disease (IBD) and the fragmented care structures and isolated academic initiatives of the time. The network’s continuing mission is to improve care for patients with Crohn’s disease and ulcerative colitis by more closely integrating clinical practice, translational science and patient involvement. This review summarises the history, governance, registries, biobanking, clinical trials, educational programmes and collaborations of the Competence Network IBD. Over the past 25 years, the Competence Network IBD has established prospective national registries (e.g. RUN-CD, RUN-UC, VEDO-IBD and FilgoColitis), developed pragmatic real-world cohorts (TARGET and GeCer) and contributed to the UMBRELLA-IBD data warehouse of the Competence Network IBD in Germany. The network played a central role in creating the German IBD DNA collection and supported the Kiel University biobank, both of which link biospecimens with longitudinal clinical data to support genetic and microbiome research. It also conducts and coordinates multicentre clinical trials and has supported the development of the German evidence- and consensus-based IBD guidelines. With more than 800 members from university centres, community practices, nursing and patient organisations, it now provides a robust platform for research and knowledge transfer across all levels of IBD care. The Competence Network IBD demonstrates how long-term interdisciplinary and cross-sectoral collaboration can improve the management of chronic inflammatory diseases. By integrating research infrastructures with education and patient involvement, the network serves as a scalable and sustainable model for national and international collaboration in IBD.

Inflammatory bowel disease (IBD) is an incurable immune-mediated inflammatory disease, affecting the gut with a high rate of primary- and secondary- loss-of-response to therapy. By investigating the T cell receptor repertoire of individuals with IBD, novel therapeutic and preventive strategies can be identified, and a better understanding of IBD can be obtained. To identify and validate T cell clonotypes implicated in the pathogenesis of IBD, we profiled the T cell receptor alpha (TRA) repertoire of three cohorts containing treatment-naive, treated individuals, and individuals living with the disease for >20 years, resulting in an exhaustive dataset containing the TRA repertoire of 1,732 individuals. Using the generated datasets, we were able to replicate previous findings describing the expansion of Crohn’s-associated invariant T (CAIT) cells in individuals with Crohn’s disease (CD) in the three cohorts. Using a hypothesis-free statistical testing framework, we identified clonotypes that were associated with the disease at its different stages, e.g., at the time of diagnosis and decades post-diagnosis. By conducting a meta-analysis across the three cohorts, we were able to identify a set of clonotypes that were associated with the disease regardless of its stage. We validated our findings in a previously published independent test dataset from a German cohort, showing the robustness of the identified clonotypes. The identified clonotypes are novel therapeutic targets to treat IBD, for example, through targeted depletion. By identifying antigens recognized by these T cells, a better understanding of the etiopathology of IBD, particularly CD, can be obtained.

Inflammatory bowel disease (IBD) is a chronic immune-mediated disorder of the gastrointestinal tract whose genetic basis is only partly resolved because most risk variants identified by genome-wide association studies (GWAS) lie in non-coding regions, limiting direct gene assignment and biological interpretation1,2. Here we analysed whole-exome and whole-genome sequencing data from 86,213 IBD cases and 478,363 controls of European ancestry. We identified 68 IBD genes directly implicated by conditionally independent protein-coding associations across the allele frequency spectrum. Many newly implicated IBD genes are supported by orthogonal genomic or pleiotropic evidence, pointing to disease-related pathways and nominating targets with therapeutic relevance. We further identified allelic series and non-additive effects at key loci such as NOD2 and TYK2. These results show that large-scale sequencing can resolve disease genes and pathways that remain ambiguous from non-coding association alone, providing a more direct route from human genetics to biological insight and therapeutic hypotheses.

Background: The efficacy and safety of the anti-TNF inhibitor golimumab in ulcerative colitis (UC) have been demonstrated in pivotal randomized controlled trials (RCTs). However, real-world data are needed to assess its effectiveness and safety in routine clinical practice, where patient populations and treatment settings are more heterogeneous. Methods: This pooled, retrospective–prospective cohort analysis draws on primary data from four IBD registries that contribute UC data to the UMBRELLA-IBD data warehouse: BioColitis, RUN-UC, TARGET-IBD, and VEDO-IBD. Data for each registry were collected across multiple centers under routine clinical care conditions in Germany. Eligible patients had a confirmed diagnosis of UC according to DGVS/ECCO criteria, were ≥18 years of age, and had newly initiated treatment with golimumab between 2017 and 2023. In total, 222 patients met these criteria and were included in the analysis. Statistical analyses included descriptive summaries, group comparisons, and Kaplan–Meier analysis of treatment persistence. Adverse events (AEs) and serious adverse events (SAEs) were also assessed and compared to other anti-TNF therapies from UMBRELLA-IBD. Results: Of the 222 patients who newly initiated golimumab, 134 had a documented month 12 visit with a documented pMayo score and were included in the modified intention-to-treat (mITT) analysis. A high proportion of the patients in the study had previously received treatment with at least two biologics (81%). In this mITT population, clinical remission was achieved in 38.1% and steroid-free clinical remission (SFCR) in 36.6% at 12 months. In the full cohort, treatment persistence at 12 months was 67.2%. Safety data on adverse events (AEs) and serious adverse events (SAEs) were reported in 14.8% and 5.8% of cases, respectively, with no significant differences compared with other anti-TNF therapies. Conclusions: In addition to the positive findings from the pivotal RCTs, these real-world data further support the clinical effectiveness and safety of golimumab in routine care for UC.

Background: Coeliac disease (CeD) is a chronic immune-mediated disease triggered by exposure to dietary gluten in genetically predisposed individuals. The burden of CeD on patients and the healthcare system remains poorly evaluated in Germany. Objectives: To assess the healthcare resource utilisation (HCRU) and costs of diagnosed CeD patients in a German claims database. Design: A retrospective CeD case–control study was conducted using German claims data between 2017 and 2021. Methods: CeD diagnosis was defined by at least one inpatient or two outpatient diagnostic codes (International Statistical Classification of Diseases and Related Health Problems, 10th Revision, German Modification (ICD-10-GM) K90.0) within four quarters (irrespective of calendar year) for CeD during the study period. Controls (non-CeD patients) were matched in a ratio of 5:1 by age, Charlson Comorbidity Index, sex and region. HCRU (hospitalisations, outpatient visits, medication use, sick leaves) and healthcare costs (outpatient services, inpatient services, outpatient pharmaceuticals, sick leaves and aids and remedies) were compared between CeD patients and controls. Results: From the 3,352,188 patients with continuous enrolment during the study period (2017–2021), 8258 (0.25%) patients were identified as having a CeD diagnosis. The mean number of hospitalisations and outpatient visits within 5 years was 1.8- and 1.5-fold higher among matched CeD patients ( n = 8243) compared to their controls ( n = 41,215), resulting in an excess healthcare cost of €5251. Inpatient expenses were the main cost driver and accounted for 31.5% of total incremental costs. Conclusion: The current study showed that CeD patients have considerably higher HCRU and related costs compared to matched controls. Our findings suggest the need for improved treatment options for CeD patients in addition to a gluten-free diet.

BACKGROUND:Real-world evidence studies of ustekinumab (UST) in ulcerative colitis (UC) are needed because randomized controlled trials do not represent unselected patient populations in everyday clinical practice. Patients with UC were recruited when starting biologic therapy for the first time or switching to a new biologic therapy. This study assessed the effectiveness of maintenance therapy with UST in comparison to anti-TNF or vedolizumab (VDZ) at 12 months. METHODS:Between 2020 and 2022, 507 UC patients starting biologic therapy for the first time or switching to a new biologic therapy were enrolled at 34 inflammatory bowel disease (IBD)-specialized centers in Germany. After excluding patients receiving other biologics or small molecules, as well as those with stomas or missing outcomes, the final sample consisted of 476 patients. The outcomes were clinical response, clinical remission (CR), and steroid-free remission. Propensity score (PS) adjustment with inverse probability of treatment weighting was used to reduce the effect of confounding due to physician selection of therapy. RESULTS:A total of 476 patients with UC were included in the analysis (UST: 147, anti-TNF: 168, VDZ: 161). Treatment persistence over 12 months differed significantly (P < .001) between UST (93.9%), VDZ (87.0%), and anti-TNF (75.0%). The PS-weighted effectiveness of UST in the mITT analysis at month 12 was not significantly different from anti-TNF or VDZ (CR: UST 26.9%, anti-TNF 34.7%, VDZ 40.9%; P = .063). CONCLUSIONS:In the prospective RUN-UC study with PS-weighted groups, UST showed higher treatment persistence but no significant difference in maintenance effectiveness compared to anti-TNF or VDZ in UC.

Abstract Background Observational real-world evidence (RWE) studies on the effectiveness of ustekinumab (UST) in ulcerative colitis (UC) are needed in addition to RCTs, which may not represent everyday clinical practice. For this reason, the prospective, controlled, propensity score (PS)-adjusted RUN-UC study was conducted on UC patients starting a new biologic therapy with a follow-up period of up to 3 years. The aim of the present analysis was to evaluate the effectiveness of 2-year maintenance therapy with UST vs. anti-TNF or vedolizumab (VDZ). Methods Between 2020-2022, 507 UC patients starting a new therapy with UST or other biologics were enrolled in 34 IBD-experienced centres in Germany. After the exclusion of patients with a stoma, small molecules and missing outcomes, the final sample consisted of 483 patients. Clinical remission (CR) (pMayo ≤ 1 plus a bleeding subscore=0) and steroid-free remission (CR and no systemic use of steroids or oral budesonide) were considered as outcomes. PS adjustment with inverse probability of treatment weighting (IPTW) was implemented to reduce confounders' effect. Results A total of 483 UC-patients [153 UST (bio-naïve: 13), 165 anti-TNF (ADA: 30.3%, IFX: 61.8%, GOL: 7.9%) (bio-naïve: 114) and 165 VDZ (bio-naïve: 106)] were included in the analysis. The PS-adjustment reduced systemic differences in the baseline parameters (UST/anti-TNF/VDZ: 43.1/46.1/50.9% males, 23.5/24.2/20.6% EIMs), in particular, the "bio-experienced" characteristic was also equalised, between the groups. Treatment persistence over 24 months showed differences between UST (68.6%), VDZ (73.3%) and anti-TNF (58.8%) (p=0.012), but this was only statistically significant for VDZ vs anti-TNF (p=0.005) but not for UST vs VDZ (p> 0.05) and UST vs anti-TNF (p>0.05) (Figure 1). The PS-weighted 24-month effectiveness (n=367) of UST (mITT analysis) in terms of clinical remission and steroid-free remission (Table 1) differed between the following groups (CR: UST 33.3%, anti-TNF 30.2%, VDZ 48.0%) compared to VDZ (p=0.031), but not compared to anti-TNF (UST vs anti-TNF p>0.05 and anti-TNF vs VDZ p=0.005). A sub-analysis evaluating steroid-free remission in bio-experienced patients after one prior anti-TNF treatment showed no statistical difference. was (UST 41.5%, anti-TNF 20.0% and VDZ 43.8%; p=0.130). Conclusion In this prospective RUN-UC study with PS-weighted groups, UST, anti-TNF and VDZ showed a more variable 24-month effectiveness, favouring VDZ over UST and anti-TNF. However, in a subgroup of bio-experienced patients with only one anti-TNF before baseline, steroid-free remission was numerically but not statistically higher with UST and VDZ than with anti-TNF.

BACKGROUND:The prospective RUN-CD registry investigates the effectiveness of ustekinumab (UST) and other biologics in Crohn's disease (CD) across Germany. Based on data from the registry, this study presents the maintenance phase results of a 12-month real-world-evidence (RWE) comparison of CD patients initiating new biologic therapies with UST or anti-TNF. METHODS:After excluding patients using biologics other than UST and anti-TNF and those with missing outcomes, the final sample consisted of 618 CD patients. Clinical remission (CR), defined as a Harvey-Bradshaw Index (HBI) ≤4, was the prespecified endpoint at 12 months. Switching to another biologic therapy was considered an outcome failure. Propensity score adjustment was used to reduce the effect of confounders. RESULTS:The study included 343 CD patients treated with UST and 264 treated with anti-TNF. Over 12 months, the frequency of therapy switches was significantly higher for infliximab (28%) compared with UST (17%) and adalimumab (17%) (P =.045). There was no significant difference in CR rates at 12 months between the UST and anti-TNF groups (65.8% vs 60.0%, P =.262). However, in week-16 responders, CR rates at 12 months were significantly higher with UST (77.6%) versus anti-TNF (65.4%) (P =.041). The change in EQ-VAS (QoL) scores between UST and anti-TNF showed a 5.1-point difference favoring UST (P =.002). CONCLUSIONS:In this 12-month RWE comparison, overall CR rates were similar between UST and anti-TNF. However, among week-16 responders, CR rates were significantly higher with UST. Additionally, UST was associated with a significantly greater improvement in QoL compared with anti-TNF.

Introduction IBD is an incurable immune-mediated inflammatory disease (IMID), affecting the gut with a high rate of primary- and secondary-loss-of-response to therapy. By investigating the T cell receptor repertoire of individuals with IBD, novel therapeutic and preventive strategies can be identified, and a better understanding of IBD can be obtained. Methods Whereas most studies have so far focused on the more diverse T cell receptor beta (TRB) repertoire, we here profiled the alpha (TRA) repertoire of three cohorts containing treatment-naïve and treated individuals in addition to individuals living with the disease for >20 years, resulting in an exhaustive dataset containing the TRA repertoire of 2,151 individuals. Results Using the generated datasets, we were able to replicate previous findings describing the expansion of Crohn’s-associated invariant T (CAIT) cells in individuals with Crohn’s disease (CD) in the three cohorts. Using a hypothesis-free statistical testing framework, we identified clonotypes that were associated with the disease at its different stages, e.g., at the time of diagnosis and decades post-diagnosis. By conducting a meta-analysis across the three cohorts, we were able to identify a set of clonotypes that were associated with the disease regardless of its stage. We validated our findings in a previously published independent test dataset from a German cohort, showing the robustness of the identified sets of clonotypes. Conclusion The identified clonotypes are potential novel therapeutic targets to treat IBD, e.g., through targeted depletion. These clonotypes are also of major interest as they can be investigated in a targeted fashion to identify culprit antigen(s) in IBD. ### Competing Interest Statement MP, DM, BH, and HR acknowledge employment by, and equity ownership in, Adaptive Biotechnologies Corp. H.E. did an internship at Adaptive Biotechnologies from July 2023 to September 2023. JH has received consulting and/or advisory board fees from: AbbVie, Alfasigma, Aqilion, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead, Hospira, Index Pharma, Janssen, Johnson & Johnson, MEDA, Medivir, Medtronic, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Prometheus Laboratories Inc., Sandoz, Shire, STADA, Takeda, Thermo Fisher Scientific, Tillotts Pharma, Vifor Pharma, UCB; and speaker's fees from: AbbVie, Alfasigma, Bristol Myers Squibb, Celgene, Eli Lilly, Ferring, Galapagos, Gilead, Hospira, Janssen, Johnson & Johnson, Merck Sharp & Dohme, Novartis, Pfizer, Shire, Takeda, Thermo Fisher Scientific, Tillotts Pharma; and research grant support from Janssen, Merck Sharp & Dohme and Takeda. G.P. has served as a speaker and/or advisory board member for AbbVie. She has also received grant support from Ferring, Tillotts Pharma, and Takeda. V.A.K. received speaker honoraria from Thermo Fischer Scientific, is a consultant for Janssen-Cilag AS, and is on the advisory Board of Tillotts Pharma AG and Takeda AS. J.R.H. received a research grant from Biogen and speaker honoraria from Roche, Novartis, Amgen, and has been a consultant for Novartis and Orkla Health, all unrelated to the present work. M.L.H. received investigator-initiated research grants from Takeda, Pfizer, Tilllotts, Ferring, and Janssen. Speaker honoraria from Takeda, Tillotts, Ferring, AbbVie, Galapagos, and Meda. She is also on the advisory board of Takeda, Galapagos, MSD, Lilly, and AbbVie. All other co-authors declare no competing interests. Deutsche Forschungsgemeinschaft, https://ror.org/018mejw64, Research Unit 5042: miTarget, The Microbiome as a Therapeutic Target in Inflammatory Bowel Diseases, Cluster of Excellence 2167 Precision Medicine in Chronic Inflammation (PMI), Collaborative Research Unit 1526 Pathomechanisms of Antibody-mediated Autoimmunity (PANTAU) Insights from Pemphigoid Diseases European Union, miGut-Health: Personalized blueprint of intestinal health (101095470) Innovative Medicines Initiative, https://ror.org/019af4n30, 831434 (3TR)

BACKGROUND AND AIMS:Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC), are known to involve shifts in the T-cell repertoires of affected individuals, including clonal expansion of abundant T-cell populations in CD mucosal tissue. There are also differential human leukocyte antigen (HLA) risk and protective alleles between CD and UC, implying CD- and UC-specific repertoire changes that have not yet been identified. In this study, we aimed to identify specific, antigen-driven T-cell signatures in CD and UC. METHODS:We performed ImmunoSequencing on blood samples from 3853 CD cases, 1803 UC cases, and 5596 healthy controls (HCs). We identified public T cell receptor β (TCRB) sequences significantly enriched in CD or UC cases. RESULTS:We determine that there is more expansion across clonotypes in CD, but not UC, compared with HCs. Strikingly, from blood, we identify public TCRBs specifically expanded in CD or UC. These sequences are more abundant in intestinal mucosal samples, form groups of similar CDR3 sequences, and can be associated with specific HLA alleles. Although the prevalence of these sequences is higher in ileal and ileocolonic CD than colonic CD or UC, the TCRB sequences themselves are shared across CD and not between CD and UC. CONCLUSIONS:There are peptide antigens that commonly evoke immune reactions in IBD cases and rarely in non-IBD controls. These antigens differ between CD and UC. CD, particularly ileal CD, also seems to involve more substantial changes in clonal population structure than UC, compared to HCs.

BACKGROUND:Mesalamine is the recommended first-line treatment for inducing and maintaining remission in mild-to-moderate ulcerative colitis (UC). However, adherence in real-world settings is frequently suboptimal. Encouraging collaborative patient-provider relationships may foster better adherence and patient outcomes. AIM:To quantify the association between patient participation in treatment decision-making and adherence to oral mesalamine in UC. METHODS:We conducted a 12-month, prospective, non-interventional cohort study at 113 gastroenterology practices in Germany. Eligible patients were aged ≥ 18 years, had a confirmed UC diagnosis, had no prior mesalamine treatment, and provided informed consent. At the first visit, we collected data on demographics, clinical characteristics, patient preference for mesalamine formulation (tablets or granules), and disease knowledge. Self-reported adherence and disease activity were assessed at all visits. Correlation analyses and logistic regression were used to examine associations between adherence and various factors. RESULTS:Of the 605 consecutively screened patients, 520 were included in the study. The median age was 41 years (range: 18-91), with a male-to-female ratio of 1.1:1.0. Approximately 75% of patients reported good adherence at each study visit. In correlation analyses, patient participation in treatment decision-making was significantly associated with better adherence across all visits (P = 0.04). In the regression analysis at 12 months, this association was evident among patients who both preferred and received prolonged-release mesalamine granules (odds ratio = 2.73, P = 0.001). Patients reporting good adherence also experienced significant improvements in disease activity over 12 months (P < 0.001). CONCLUSION:Facilitating patient participation in treatment decisions and accommodating medication preferences may improve adherence to mesalamine. This may require additional effort but has the potential to improve long-term management of UC.

Abstract Background Treatment options for patients with ulcerative colitis have increased considerably in recent years. Here, we present the 6-month results on clinical effectiveness and psycho-social outcomes of the ongoing FilgoColitis study in patients with ulcerative colitis (UC) starting new treatment with filgotinib (FIL) in a real-world setting. Methods FilgoColitis is a prospective, multicentre, non-interventional, 24-month observational study in patients with active UC and newly introduced FIL therapy. Disease activity (clinical response: reduction of pMayo by ≥3 points from baseline to month 6 and a reduction of at least 30% or reaching remission at month 6; clinical remission (CR): pMayo ≤ 1 plus a bleeding subscore=0; steroid-free remission: CR and no systemic use of steroids or oral budesonide), quality of life (QoL) (sIBDQ and EQ-5D), and fatigue level (FACIT-F) will be analyzed. In a subgroup, the daily step count was recorded using the SensMotion® thigh accelerometer for at least 3 days after each visit (n=21). Results 202 patients were enrolled in the study. After excluding missing outcomes, 164 patients were available for the 6-month analysis. Of these, 61.0% were male, and the median time since diagnosis was 8.0 years. Before treatment with FIL, 85.4% of patients had received biologic or small molecule therapies, and 57.3% had used immunosuppressants. Treatment persistence at month 6 was 87.2% (Fig. 1). After 6 months of treatment with FIL, the clinical response and remission rate were 59.2% and 41.7%, respectively (mITT (switchers=outcome failures), Table 1). There was no significant difference in clinical remission between biologic-naïve and biologic-experienced patients (41.7% vs 41.4%). Looking at week-10 responders only, the response rate at month 6 was 85.0%, and the remission rate was 58.8%. QoL improved significantly, with median EQ-VAS scores increasing from 64 to 80 at month 6 (p<0.001), and sIBDQ scores improving from 42.0 to 56.0 (p<0.001). Fatigue scores improved significantly from baseline to month 6 of FIL therapy (FACIT-F score part I: 8.0 vs 5.0, p<0.001). In patients who were in remission at month 6, the daily number of steps measured was higher than in patients who were not in remission (9918 (4861-11048) vs 5959 (4747-6323)). The steps measured during the night also differed between these two groups: 196 (142-559) vs 293 (164-479). This was consistent with asking the patients if they had nocturnal stools (0% vs 42.9%). Conclusion In this real-world study, FIL showed a clinical response rate of 59% and a clinical remission rate of 42% at month 6 in patients with active UC, demonstrating a further improvement compared to the induction phase. QoL was also significantly improved.

Primary sclerosing cholangitis (PSC) is an idiopathic, progressive and incurable liver disease. Here, we aimed for systematic analyses of adaptive immune responses in PSC. By profiling the T cell repertoires of 504 individuals with PSC and 904 healthy controls, we identified 1,008 clonotypes associated with PSC. A substantial fraction of these clonotypes was restricted to known PSC human leukocyte antigen susceptibility alleles and known to target Epstein-Barr virus (EBV) epitopes. We further utilized phage-immunoprecipitation sequencing to determine antibody epitope repertoires of 120 individuals with PSC and 202 healthy controls, which showed a higher burden of anti-EBV responses in PSC than controls. EBV-specific monoclonal antibodies isolated from B cells in PSC livers corroborated convergent B and T cell responses against EBV. By analyzing electronic health records of >116 million people, we identified an association between infectious mononucleosis and PSC (odds ratio, 12; 95% confidence interval, 6.3-22.9), suggesting a link between EBV and PSC.

OBJECTIVES:Celiac disease (CeD) is a life-long systemic immune-mediated disorder. Data on burden and cost of CeD in children are scarce. We assessed healthcare resource utilization (HCRU) and cost of healthcare services of newly diagnosed children in Germany. METHODS:This retrospective case-control study covered a period from 2014 to 2021, using German Statutory Health Insurance claims data from the "Institute for Applied Health Research Berlin" (InGef). The HCRU (hospitalizations, outpatient contacts, outpatient drug prescriptions) and cost of CeD patients aged <6 (group 1) and 6-11 years (group 2) between 2017 and 2019 were compared with matched non-CeD individuals (1:5 matching by age, sex, Charlson Comorbidity Index, and region) during the time of diagnosis and 2 years thereafter. Case definition required ≥1 diagnosis of CeD (ICD-10-GM K90.0) as inpatient or ≥2 recorded diagnoses as outpatient plus ≥1 CeD-related serological test, and no recorded CeD diagnoses during the 3-year preobservation period. RESULTS:We identified 410 CeD cases resulting in incidence rates of 32.5 and 34.1 per 100,000 individuals in groups 1 and 2, respectively. During time of diagnosis and 2 years thereafter, CeD patients had increased HCRU (median) compared to their controls (two more hospitalizations, almost three-times more outpatient contacts, and 3-4 more prescriptions), resulting in higher total costs (median difference €1677 and €1343 in group 1 and 2, respectively) (all p < 0.001). CONCLUSIONS:These findings underscore the substantial burden of CeD on patients and healthcare systems, highlighting the need for targeted interventions and effective management strategies to mitigate this impact.