Irina Blumenstein

^* Die Autoren haben in gleicher Weise zur Erstellung des Manuskripts beigetragen. Received: 25 November 2025 Accepted: 08 December 2025 Article published online: 22 June 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

INTRODUCTION: Normalized quality of life represents a crucial long-term treatment goal in Crohn's disease (CD). We evaluated the effect of risankizumab (RZB) vs ustekinumab (UST) on achieving clinically meaningful improvements in patient-reported outcomes in the phase 3b head-to-head SEQUENCE study. METHODS: Adults with moderate-to-severe CD whose previous anti-tumor necrosis factor therapy failed were randomized 1:1 to recommended induction and maintenance doses of RZB or UST. The proportion of patients who achieved Inflammatory Bowel Disease Questionnaire (IBDQ) response, IBDQ remission, and improvements in 36-item short-form health survey physical and mental component summary (physical component summary and mental component summary, respectively) scores was evaluated at weeks 24 and 48. The proportion of patients experiencing improvement in select symptoms of the IBDQ was reported. RESULTS: Analysis included 520 patients (RZB: N = 255; UST: N = 265). At week 24, greater proportions(all P ≤ .01) of RZB- vs UST-treated patients achieved IBDQ response (75.3% vs 64.2%), IBDQ remission (52.5% vs 30.9%), and improvements in 36-item short-form health survey physical component summary (65.9% vs 53.2%). At 24 weeks, lower proportions (all P ≤ .05) of RZB- vs UST-treated patients experienced fatigue (51.4% vs 69.1%), difficulty sleeping (37.7% vs 54.3%), depression (34.1% vs 42.6%), anxiety (34.1% vs 49.8%), and bowel urgency (27.1% vs 40.0%) all of the time to some of the time. Improvements were sustained through week 48. DISCUSSION: RZB was more effective than UST in achieving sustained clinically meaningful patient-reported outcome improvements including IBDQ response and remission, and in reducing frequency of select symptoms of the IBDQ through week 48 among patients with moderate-to-severe CD.

Background/Objectives: Predicting treatment persistence in inflammatory bowel disease (IBD) remains challenging despite a broadened therapeutic arsenal. This study used longitudinal data to assess drug persistence across four biologics for IBD prior to Interleukin (IL)-23 blocker approval. Methods: We retrospectively analyzed IBD outpatients at Goethe University Hospital. Laboratory data and treatment adherence were collected to determine how many patients continued each biological therapy after induction and at 1 year. Results: Of 587 patients, those on azathioprine or mercaptopurine were excluded (focusing on biologics). Four biologicals were analyzed: 280 patients received one of them; 312 (53.2%) had Crohn’s disease and 275 (46.8%) had Ulcerative Colitis. Infliximab (IFX) was given to 93 patients (median 912 days; range 20–5273); at endpoint, 39 (42.4%) remained on IFX. Adalimumab (ADA) was used by 165 patients (median 1051 days; range 48–4458); 87 (52.4%) remained at endpoint. Vedolizumab (VDZ) included 116 patients (median 717 days; range 0–2204); 75 (64.4%) remained at endpoint. Ustekinumab (UST) was given to 62 patients (median 660 days; range 50–1399); 51 (83.6%) remained at endpoint. Some patients were exposed to multiple biologicals, contributing to smaller numbers for newer drugs. When evaluated as a first-line biological, UST (median 787 days) and VDZ (median 756.5 days) had the shortest durations, while TNF-α blockers (ADA, IFX) showed the greatest resistance as first-line therapy. Conclusions: Most patients stayed on their initial therapy after induction and at 1 year. These findings support the sustained use of established biological therapies as cost-effective, steroid-sparing options even after IL-23 approval and may inform patient counseling and long-term pharmacoeconomic considerations.

Background: Optimized drug sequencing is an emerging area of interest in the treatment of ulcerative colitis (UC). Comparative real-world data on treatment response to mirikizumab in a cohort with exposure to multiple biologic agents, particularly tumor necrosis factor (TNF)-naïve versus TNF-treated patients, remain limited. This study evaluated the therapeutic response to mirikizumab treatment in a cohort of patients with UC who were refractory to biologic therapy. Methods: Consecutive patients with UC treated with mirikizumab between July 01, 2023, and May 31, 2025, at a tertiary university referral center were retrospectively analyzed. The primary endpoint was 12-week clinical remission. The secondary endpoints included clinical remission and biochemical remission between weeks 24 and 50 and between weeks 60 and 80. Results: This study included 52 patients. Among them, 17 (32.7%) had previous exposure to ≥3 biologic agents/small molecules. The 12-week clinical remission rate was 35 of 52 patients (67.3%). There was a significant association between the treatment duration and clinical and biochemical remission. The likelihood of achieving clinical remission was 5.583 times higher after 12 weeks of intravenous mirikizumab treatment (odds ratio [OR] = 5.583, p = 0.002). Anti-TNF pretreatment had a positive effect on biochemical remission (OR = 3.489, p = 0.021). Janus kinase inhibitor pretreatment had a negative effect on clinical remission (OR = 0.19, p = 0.019). Conclusion: Mirikizumab treatment had good short- and long-term efficacy in patients with UC who previously received biologic therapy. In particular, patients with prior anti-TNF therapies had favorable biochemical remission outcomes.

Background: Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation affecting the gastrointestinal tract and extraintestinal organs. The etiology of IBD is multifactorial, involving genetic, immunological, and environmental factors. Over 200 genetic loci have been associated with the disease, indicating a significant genetic predisposition. Despite advances in understanding its genetic basis, clinical management remains challenging due to heterogeneity in disease presentation and variable treatment responses. Current therapies, such as 5-aminosalicylates and biologics, are not universally effective, underscoring the need for reliable biomarkers to predict therapeutic responses. Objective: This study investigates the potential role of interferon regulatory factor 5 (IRF5) in the pathogenesis of IBD, with a particular focus on UC. Methods: We conducted a systematic analysis of colon biopsies from 30 adult patients diagnosed with UC and from 8 non-IBD controls. Immunostaining was performed to assess IRF5 expression in colonic tissues using the primary IRF5 antibody (1:300, Abcam, ab181553). Statistical analyses evaluated the correlation between IRF5-positive cell counts, disease activity, and inflammatory markers such as calprotectin. Results: Our analysis revealed a significant increase in IRF5-positive macrophage-like cells in the inflamed mucosa of IBD patients compared to healthy controls. The number of IRF5-positive cells showed a positive correlation with disease activity and calprotectin levels, indicating that higher IRF5 expression is associated with increased inflammation. Conclusions: This study demonstrates a significant correlation between IRF5 expression and disease activity in UC, suggesting that IRF5 may play a crucial role in the inflammatory processes of the disease. The findings propose IRF5 as a novel biomarker for therapeutic intervention in IBD. Further research is needed to clarify the mechanisms by which IRF5 contributes to IBD pathogenesis and to explore the therapeutic potential of targeting this pathway in clinical settings.

Background: Patients with inflammatory bowel disease (IBD) often suffer from extra-intestinal manifestations in addition to intestinal symptoms. One of these is fatigue. Fatigue is described as persistent tiredness with episodes of sudden energy loss, which cannot be relieved by rest or sleep and has a huge impact on quality of life. The aim of this study is to identify possible risk and influencing factors for the development of fatigue in IBD. Methods: For this purpose, a questionnaire survey was conducted at two German university outpatient clinics for IBD (n = 164). Based on this, the frequency and impact of fatigue on daily life was assessed and analyzed in relation to various health parameters such as patient gender, age, disease activity, and laboratory parameters. Results: Of the 164 patients, 86 were men (52.4%) and 78 were women (47.6%). A total of 75 (45.7%) patients had ulcerative colitis, 84 (51.2%) suffered from Crohn’s disease, and 5 (3.0%) had IBD-unclassified. A total of 17 out of the 164 (10.4%) patients denied that fatigue had affected their daily activities in the past two weeks. None of the examined health parameters had a significant impact on fatigue. Conclusions: Fatigue is a common syndrome in IBD patients and affects their daily activities and quality of life. The results of the present study emphasize the need for further research for a better scientific understanding of fatigue in IBD.

Background: With the COVID-19 pandemic, a rapid adoption of telemedicine became necessary. Data regarding its implementation in specialized hepatology/IBD care remain limited. This study evaluated telemedicine’s effectiveness and safety during the pandemic at a German tertiary center and explored its integration into future hybrid care models. Methods: In a retrospective study, we analyzed 3147 patient encounters at the outpatient clinic of the Department for Gastroenterology and Hepatology at the University Hospital Frankfurt between March and June 2020. We assessed patient characteristics, appointment adherence, and outcomes across the three specialized clinics: hepatology (n = 1963), liver transplant (n = 594), and IBD (n = 590). Multivariate regression analysis identified predictors of successful telemedicine utilization. Results: Out of all appointments, 1112 (35.3%) were conducted via telemedicine, with significantly different adoption rates across clinics (hepatology, 40.4%; liver transplant, 32.8%; IBD, 21.0%, p < 0.01). Adherence rates were comparable between telemedicine (91.3%) and in-person visits (90.5%). Multivariate analysis identified age (OR 1.009, 95%CI 1.004–1.014, p < 0.001), metabolic-associated steatotic liver disease (OR 1.737, 95%CI 1.400–2.155, p < 0.001), and post-liver transplant status (OR 1.281, 95%CI 1.001–1.641, p = 0.049) as independent predictors of successful telemedicine utilization. HBV/HDV coinfection (OR 0.370, 95%CI 0.192–0.711, p = 0.003) and required endoscopy (OR 0.464, 95%CI 0.342–0.630, p < 0.001) were associated with in-person care. Hospitalization rates were low and comparable across modalities, confirming telemedicine’s safety. Conclusions: This study demonstrates that telemedicine can be successfully implemented in specialized gastroenterology and hepatology care, with high compliance rates comparable to in-person visits. Patient characteristics and disease-specific factors influence the suitability for telemedicine, supporting a stratified approach to hybrid care models, which can optimize resource utilization while maintaining quality of care. Particularly stable MASLD patients, well-controlled post-transplant recipients beyond one year, and IBD patients in sustained remission can be properly managed through telemedicine with annual in-person assessments.

Background: Inflammatory bowel disease (IBD) remains an incurable illness. Patients with IBD show gender-specific differences in various aspects of the disease. There is still uncertainty about the causality of the differences. Methods: The aim of this study was to determine the most relevant psychophysiological gender-specific differences in IBD. For this purpose, a questionnaire survey was conducted on disease activity and psychological concomitant diseases in patients with IBD (n = 300). Among the 218 patients with IBD who provided gender information, both genders were equally distributed. Results: Females with IBD are significantly more affected by IBD-related symptoms than men. Disease activity Scores Harvey-Bradshaw Index (HBI), Partial Mayo Score (pMAYO) showed no significant differences between the sexes in the subgroups with CD (HBI, m: 3 (IQR 1–6), w: 4 (IQR 2–8), p = 0.0677) and UC (pMAYO, m: 1 (IQR 0–4), w: 3 (IQR 0–5), p = 0.2118). IBD Questionnaire (IBDQ)shows significant differences in the gender-specific analysis. The mean value of the IBDQ total score of the female participants was 4.4 (SD 1.1) and that of men was 5.0 (SD 1.0) (p = 0.0002). Conclusions: There is a great need to investigate the causality of gender-specific differences in greater depth.

Background: Vedolizumab (VDZ) for subcutaneous (SC) injection was approved for use in Europe in 2020 and the US in 2023. Promising efficacy and tolerability have been proven in pivotal trials. However, real-world data on the SC use of VDZ, especially in patients with active disease, are still lacking. We aimed to determine treatment persistence and the drug’s efficacy in inflammatory bowel disease (IBD) patients with active disease in comparison to patients in clinical remission. Methods: Patients treated for IBD in a tertiary care center from July 2020 to December 2021 were included in this study. Clinical and biochemical parameters and data on treatment adherence were collected. VDZ trough levels and disease activity before and after the switch from intravenous (IV) to SC injections were monitored during routine checkups and were retrospectively analyzed. The patients were followed up until week 20. Results: Eighty-two patients were included in the study. Of them, 35 patients had active disease (35/82 = 43%) at the time of the switch and 47 patients (47/82 = 57%) were in remission. In total, 10 patients experienced switch failure, 5 were switched back to IV VDZ, and 5 were swapped to a different biologic agent. We observed an increase in VDZ trough levels from the switch to week 8 and from the switch to week 20 in the remission group. Vedolizumab trough levels of 7.4, 51.4, and 33.45 ug/mL at the switch, week 8, and week 20 were identified to discriminate between remission and disease activity in our cohort. There was no new safety signal detected during the study period. Conclusions: The switch from IV to SC VDZ proved to be efficient, safe, and even capable of reducing residual disease activity.