Background and Aims: The IL-12/23 inhibitor ustekinumab (UST) opened up new treatment options for patients with Crohn’s disease (CD). Due to the recent approval, real-world German data on long-term efficacy and safety are lacking. This study aimed to assess the clinical course of CD patients under UST therapy and to identify potential predictive markers. Methods: Patients with CD receiving UST treatment in three hospitals and two outpatient centers were included and retrospectively analyzed. Rates for short- and long-term remission and response were analyzed with the help of clinical (Harvey–Bradshaw Index (HBI)) and biochemical (C-reactive protein (CRP), Fecal calprotectin (fCal)) parameters for disease activity. Results: Data from 180 patients were evaluated. One-hundred-and-six patients had a follow-up of at least eight weeks and were included. 96.2% of the patients were pre-exposed to anti- TNFα agents and 34.4% to both anti-TNFα and anti-integrin antibodies. The median follow-up was 49.1 weeks (95% CI 42.03-56.25). At week 8, 51 patients (54.8%) showed response to UST, and 24 (24.7%) were in remission. At week 48, 48 (51.6%) responded to UST, and 25 patients (26.9%) were in remission. Steroid-free response and remission at week eight was achieved by 30.1% and 19.3% of patients, respectively. At week 48, 37.6% showed steroid-free response to UST, and 20.4% of the initial patient population was in steroid-free remission. Conclusion: Our study confirms short- and long-term UST effectiveness and tolerability in a cohort of multi-treatment-exposed patients.

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.