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Background: Obesity in patients with IBD is increasing, accompanied by an increase in metabolic comorbidities. Although GLP-1 agonists have shown promise in weight reduction, their efficacy and safety in patients with IBD are underexplored. This study evaluated the impact of GLP-1-based therapies on weight loss and metabolic parameters in non-diabetic patients with IBD., Methods: We conducted a single-center observational cohort study that included adult patients with IBD who were started on GLP-1-based therapy (semaglutide or tirzepatide) for weight loss from January 2021 to April 2024. The primary outcomes were changes in BMI and total body weight. Secondary outcomes included tolerability, safety, and changes in metabolic risk factors., Results: The study included 36 patients with IBD, predominantly female (64%), with a median age of 45.5 years (IQR 41-51.5 years). The majority (67%) had Crohn's disease (CD) and on advanced therapy (86%). BMI significantly decreased from 34.0 (IQR 31.0-38.2) to 31.0 (IQR 29.0-36.1) with GLP-1-based therapy (p < 0.0001). Total body weight (TBW) significantly decreased by a median of 8.15 kg (IQR 15.9-2.2 kg; p < 0.0001). Although a decrease in total cholesterol and glycated hemoglobin was seen, this was not statistically significant (p = 0.0634 for total cholesterol, p = 0.0536 for glycated hemoglobin). No significant changes were observed in ALT or CRP levels. The most common side effects were nausea (31%) and constipation (25%)., Conclusions: Semaglutide and tirzepatide can effectively reduce BMI in non-diabetic patients with IBD with manageable side effects. However, further studies are required to explore the long-term safety of GLP-1 agonists in the IBD population., Competing Interests: Declarations. Conflicts of interest: SP: SP has served as a consultant for Noro Nordisk and Lilly, she receives research support from Amgen and Novo Nordisk, she is in the Speaker’s Bureau for Novo Nordisk and Lilly. JSP, JK, NKC, EF: No conflicts of interest to disclose. Ethical approval: This study was reviewed and approved by the Institutional Review Board (IRB, Ethics Board) at the University of Chicago. Each subject provided informed consent (IRB protocol 15573A)., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The Endoscopic Healing Index (EHI) analyzes biomarkers in a patient's peripheral blood to assess mucosal healing. We aimed to characterize the effectiveness of the EHI as a predictor of disease activity in a real world clinical setting., Methods: This retrospective study looked at patients treated and followed up at the University of Chicago Medicine IBD center who had EHI tests done as part of routine clinical care. The results of the EHI were compared with radiological imaging or endoscopy performed within 3 months of the EHI in order to determine accuracy at diagnosing active inflammation., Results: Fifty-five patients with CD and with an available EHI were included in this study. Four (50%) patients with an EHI of < 20 (n = 8) had evidence of objective inflammation. A cutoff of ≤ 20 had a sensitivity of 89% and specificity of 23.5% for predicting no evidence of any objective inflammation with an AUROC of 0.69. This score had a negative predictive value (NPV) of 50% and positive predictive value (PPV) of 72.3%. A cutoff EHI of 30 tended to classify patients as either having objective evidence of inflammation or not more often than FCAL (Correctly classifying inflammation: 89% vs 64%, respectively; p = 0.32)., Conclusion: In this real world analysis, the EHI showed poor predictive value for the absence of active inflammation as assessed by imaging or endoscopy, has limited utility in confirming deep remission and should be used with another objective modality., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Ongoing efforts to break the therapeutic ceiling in inflammatory bowel disease include combination therapy approaches. Dual-targeted therapy (DTT) has been reported in case reports and small case series. This report describes our experience with ustekinumab (UST) and upadacitinib (UPA) as DTT in patients with Crohn's disease (CD)., Methods: In this retrospective, observational study, we reviewed medical records of patients with CD treated with combined UST and UPA between April 2021 and July 2022. Clinical remission was defined as Harvey-Bradshaw Index (HBI) ≤ 4, and clinical response was defined as decrease in HBI ≥ 3 or physician's assessment of clinical response., Results: We identified 10 CD patients treated with UST/UPA, with median follow-up period of 10 months (interquartile range (IQR) 7.3-12). Median age was 35.5 years (IQR 28.3-43.8) and median number of prior biologic treatment exposures was 4 (IQR 4-5). Indications for UST/UPA were active CD (n = 6), extraintestinal manifestations (EIM) (n = 2), and both active CD and EIM (n = 2). Five of six patients with active CD achieved clinical remission with UST/UPA. Two patients with active EIM (joint pain) achieved resolution of their symptoms. One patient exhibited improvement in both conditions. Three patients developed mild respiratory symptoms and one experienced bowel obstruction. Two patients developed nausea resulting in de-escalation of treatment interval or discontinuation altogether., Conclusion: Based on our case series, combination therapy with UST and UPA may be effective and appears safe in refractory Crohn's disease and for patients with co-existing extraintestinal manifestations., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Ozanimod is a first-in-class Sphingosine-1-phosphate (S1P) receptor modulator approved for the treatment of moderately to severely active ulcerative colitis (UC). Real world data describing use of ozanimod are limited., Aim: To provide 1-year follow-up results of our UC patient cohort treated with ozanimod., Methods: This prospective, observational cohort study includes consecutive patients who initiated ozanimod at the University of Chicago IBD Center between 5/2021 and 12/2022. We collected demographic, clinical, and laboratory data. Clinical disease activity was prospectively assessed using the Simple Clinical Colitis Activity Index., Results: Forty-five patients with UC initiated ozanimod therapy and were included in the effectiveness analysis. The median age was 35 years (interquartile range (IQR) 28-52), median disease duration of 6 years (IQR 3-13), 26 (58%) were male, 23 (51%) had extensive colitis, 34 (76%) had previous advanced therapy exposure. Thirty-four patients had clinically active UC at the time of ozanimod initiation; week 10 clinical response and remission rates were 58% and 53%, respectively. By week 52, the rates were 25% for both clinical response and remission. In the 12 (39%) patients with a > 75% reduction in absolute lymphocyte count, numerically greater induction clinical response and remission rates were observed (80% vs 54%, p = 0.4 and 75% vs 53%, p = 0.4, respectively). There were no episodes of symptomatic bradycardia and no other new safety signals., Conclusion: Ozanimod effectively induced clinical response and remission patients with largely treatment refractory UC, however, had modest long-term effectiveness. The safety profile was favorable with no new signals., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)