Rosentreter, Ryan E.

Abstract Background & Aims Stricturing Crohn’s disease (CD) is a significant problem, and no selective anti-fibrotic therapies are available. Anti-inflammatory approaches are the mainstay of medical treatment. However, data on the efficacy of ustekinumab (USTE) in ileal stricturing CD are lacking. Our aim was to assess its efficacy in this setting. Methods We performed an international multicenter observational cohort study evaluating adult CD patients who received USTE within 6 months of imaging-confirmed symptomatic stricturing small bowel disease. Outcomes were rates of endoscopic balloon dilation (EBD), surgery, intervention (defined as the composite need for EBD or surgery), recurrent obstructive symptoms, and USTE persistence. Results Fifty-seven patients were included (51% female, median age 43 years). Median follow-up was 17 months. Intervention rates were 35%, 45%, and 69% of patients, at 12, 24, and 48 months, respectively. USTE persistence was 78%, 76%, and 52% at 12, 24, and 48 months. Estimated obstructive symptoms rates were 31% and 49% at 12 and 24 months, respectively. EBD within 6 months prior to starting USTE was associated with an increased risk of intervention. Increased bowel wall thickness on imaging, prior biologic use, and obstructive symptom duration were associated with USTE discontinuation. Occurrence of obstructive symptoms during treatment was associated with prior biologic use, EBD within 6 months of starting USTE, and a lower BMI. Conclusions USTE appears to be an appropriate medical option in biologic-experienced CD patients with ileal strictures. Further prospective data are needed to better define outcomes and predictors of response in this setting.

Abstract Background Colonic strictures in Crohn’s disease (CD) are an important, but understudied clinical problem. Cross-sectional imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), and intestinal ultrasound (IUS) effectively assess the small bowel in CD allowing for the diagnosis of strictures. However, radiologic definitions of colonic strictures and their diagnostic accuracy have not been developed. Endoscopic definitions of colonic strictures are the most well-described. Aims We aimed to systematically review available data to summarize definitions, diagnosis and differentiation between inflammation and fibrosis of colonic strictures on endoscopy, CT, MR, and IUS Methods We conducted a systematic review following PRISMA guidelines using MEDLINE, Scopus, CINAHL, and CENTRAL databases from inception to Oct 6, 2024 to identify literature with diagnostic imaging that included patients with colonic CD strictures. To distinguish fibrosis from inflammation, only studies comparing endoscopy or imaging to a full thickness histologic gold standard were included. Two stage screening was completed in duplicate, and risk of bias was assessed using QUADAS-2 Results 46 studies were eligible for inclusion. Definitions for colonic strictures on CT, MR, and IUS are heterogeneous with combinations of bowel wall thickness, luminal narrowing, and pre-stenotic dilation with no clear cut offs. Endoscopic definitions commonly included lack of colonoscope passage through a narrowed lumen. The diagnostic accuracy of colonic strictures on imaging to detect inflammation and fibrosis against a gold standard of endoscopy or surgical resection is unclear as direct comparisons are few. Meta-analyses were not conducted due to methodological heterogeneity of grading fibrosis and statistical heterogeneity of sensitivity, specificity, and accuracy of colonic stricture diagnoses limited by pooling with small bowel strictures in the studies Conclusions This systematic review describes a lack of definitions for the diagnosis of CD colonic strictures particularly on diagnostic imaging, and the limitations with the current available data to differentiate inflammation from fibrosis. Although bowel wall thickening, luminal narrowing, and pre-stenotic dilation are recognized as hallmark features of small bowel strictures, their adaptation to the colon requires further assessment. Definitions for colonic strictures should likely include imaging combined with endoscopy. Future endeavors are required to develop a consensus to define and diagnose colonic strictures on these modalities Funding Agencies None

Abstract Background Colonic strictures in Crohn’s disease (CD) present a complex and relatively underexplored clinical issue. Imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), and intestinal ultrasound (IUS), have established criteria for evaluating small bowel CD strictures. However, radiologic definitions of benign colonic strictures and their diagnostic accuracy are not well-developed. Endoscopic definitions of colonic strictures are the most well-described. We conducted a systematic review to summarize definitions, diagnosis, and identification of inflammation and fibrosis of colonic strictures on endoscopy, CT, MR, and IUS. Methods A systematic review following PRISMA guidelines, from inception to October 6, 2024, was conducted using MEDLINE, Scopus, CINAHL, and CENTRAL databases to identify literature on diagnostic imaging of patients with colonic CD strictures. Only studies with comparison to endoscopy or imaging to a full-thickness histologic gold standard to differentiate fibrosis from inflammation were included. Two stage screening was completed in duplicate, and risk of bias was assessed using QUADAS-2. Results 46 studies were eligible for inclusion of 4623 abstracts screened. Definitions of colonic strictures on CT, MR, and IUS were highly variable with combinations of bowel wall thickness, luminal narrowing, and pre-stenotic dilation. Endoscopic definitions of colonic strictures were the most consistently reported as lack of passage of a colonoscope through a narrowed lumen. Diagnostic imaging definitions used various combinations of increased bowel wall thickness, luminal narrowing, and pre-stenotic dilation with no clear cutoffs. Few studies directly compared imaging features with histologic or endoscopic gold standards, limiting evaluation of diagnostic accuracy. Meta-analyses were not conducted due to methodological heterogeneity of grading fibrosis across studies. In addition, statistical heterogeneity of sensitivity, specificity, and accuracy of colonic stricture diagnoses was limited by pooling with small bowel strictures in the studies. Conclusion This systematic review highlighted the absence of standardized definitions for diagnosing colonic Crohn’s disease strictures, particularly on diagnostic imaging, and the limited data distinguishing inflammatory from fibrotic components. Bowel wall thickening, luminal narrowing, and pre-stenotic dilation are key features of small bowel strictures, but their relevance to the colon requires further assessment. Establishing standardized definitions for colonic strictures that incorporate both endoscopic and imaging modalities is essential to advancing the field. Conflict of interest: Dr. Lu, Cathy: Advisory board - Abbvie, Johnson and Johnson, Takeda, Ferring, Merck, Celltrion, Lilly, Pfizer, Pendopharm, Agomab. Research Funding - Abbvie, Helmsley Charitable Trust, Alberta Innovates Dhaliwal, Ravdip: No conflict of interest Kellar, Amelia: No conflict of interest Rowan, Catherine: No conflict of interest St-Pierre, Joelle: Consultant for Pfizer, Abbvie, Eli Lilly and Pendopharm, and speaker for Takeda. Ernest-Suárez, Kenneth: Consulting/Advisory Board fees: Abbvie, AstraZeneca, Johnson & Johnson, Pfizer, Ferring, Sandoz, SatisfAI, Takeda O’Brien, Maureen: No conflict of interest Rosentreter, Ryan: No conflict of interest Gulhati, Vishrut: No conflict of interest Baker, Mark: No conflict of interest Bettenworth, Dominik: DB is on the advisory board or consultant for AbbVie, Amgen, Arena, Atheneum, BNG Service GmbH, Bristol Myers Squibb, CED-Service GmbH, Celltrion, Doctorflix, DGVS, Diaplan, Else Kröner-Fresenius Foundation, Falk Foundation, Galapagos, Guidepoint, Impulze, Ferring, Janssen Cilag, Lilly, Medical Tribune, MedTriX, MSD, Mylan, Onkowissen, Pharmacosmos, Pfizer, Roche, Sandoz, Takeda, Tetrameros, Thieme, Tillotts Pharma, UCB Biopiharma, Viatris and Vifor Pharma. Bruining, David: Advisory board fees from Janssen Bari, Dane: Grant from Helmsley Charitable Trust speaker honorarium from Siemens Healthineers support for attending meetings or travel from Siemens Healthineers member of the Olympus advisory board co-chair Society of Abdominal Radiology (SAR) Inflammatory Bowel Disease Disease Focused Panel (IBD DFP) and SAR Photon-Counting Detector CT Emerging Technology Commission and chair of the Society for Advanced Body Imaging Scientific Committee. Dillman, Jonathan: Grants from Philips Healthcare, GE HealthCare, Motilent, Perspectum, Guerbet, and Bracco. El Ouali, Sara: Speaker and/or consulting fees from Takeda, Eli Lilly, Janssen, Abbvie. Fletcher, John: Grant supports from Siemens Healthineers Gordon, Ilyssa: Grants to institution from Morphic Therapeutics, Alimentiv, Pliant Therapeutics, and UCB patent pending with Case Western Reserve University on radiomics signatures Jairath, Vipul: Consulting Fees: Abbvie, Alimentiv, Amgen, Anaptys Bio, Asahi Kasei, Asieris, Astra Zeneca, Attovia, Blackbird Labs, BMS, Boehringer Ingleheim, Biomebank, Caldera, Calluna, Catalytic Health, Celltrion, Ensho, Enthera, Exeliome Biosciences, Ferring, Fresenius Kabi, Gilead, Granite Bio, GSK, Janssen, Lilly, Merck, Mountainfield, MRM Health, Nxera, Organon, OSE Immunotherapeutics, Pendopharm, Pioneering Medicine, Pfizer, Prometheus, Roche/Genentech, Sanofi, SCOPE, Shattuck Labs, Sorriso, Spyre, Synedgen, Takeda, Teva, Tillotts, Union Therapeutics, Ventus, Ventyx, Vividion, Xencor, Zealand Pharma. Feagan, Brian Gordon: Consulting Fees: AbbVie, Abivax, Adaxion, Adiso, AgomAB Therapeutics, Akros, Alira Health, Ally Bridge Group, Apini Therapeutics, Argenx, Attovia Tx, Avoro Capital Advisors, Belmore Law, Biora Therapeutics, Blackbird Laboratories, Boehringer-Ingelheim, BMS, Boxer Capital, Celgene/BMS, Clarivate, Connect Biopharm, EcoR1, Eli Lilly, Ensho Therapeutics, Equillium, Evida, Enveda, Evommune Inc. Faes Farma, First Wave, Forbion, Galapagos, Genentech/Roche, General Atlantic, Genesis Therapeutics, Gerson Lehrman Group, Gilead, Guidepoint, Imhotex, ImiDomics, Immunic Therapeutics, Janssen, Japan Tobacco Inc., LifeMine Therapeutics, Mage Biologics, Merck, Mirador Therapeutics, Mobius Care, Monte Rosa Tx, Morphic Therapeutics, Nimbus Therapeutics, Novartis, Nxera, OncoC3, Palisade Bio, Pendopharm, Pfizer,Q32 Bio, REDX, Roche, Sanofi, Sobi, Sorriso, Spyre Therapeutics, Sun Pharma, Surrozen Inc., Synedgen, Takeda, Tegus Inc., Teva, Tillotts, Trex Bio, TR1X Inc. TVM Lifesciences, Ventyx Biosciences, Versant Ventures, Vida Ventures, Ysios Capital, Zagbio Stock Shareholder: Connect Biopharm, EnGene, Evida, SRT, Imidomics, Enveda Rieder, Florian: Personal Fees: Adiso, Adnovate, Agomab, Allergan, AbbVie, Arena, Astra Zeneca, Boehringer-Ingelheim, Celgene/BMS, Celltrion, CDISC, Celsius, Cowen, Ferring, Galapagos, Galmed, Genentech, Gilead, Gossamer, Granite, Guidepoint, Helmsley, Horizon Therapeutics, Image Analysis Limited, Index Pharma, Landos, Jannsen, Koutif, Mestag, Metacrine, Mopac, Morphic, Organovo, Origo, Palisade, Pfizer, Pliant, Prometheus Biosciences, Receptos, RedX, Roche, Samsung, Sanofi, Surmodics, Surrozen, Takeda, Techlab, Teva, Theravance, Thetis, UCB, Ysios, 89Bio

Summary Background Stricturing Crohn's disease (CD) occurs most commonly in the terminal ileum and poses a clinical problem. Cross‐sectional imaging modalities such as intestinal ultrasound (IUS), computed tomography enterography (CTE), and magnetic resonance enterography (MRE) allow for assessment of the entire bowel wall and associated peri‐enteric findings. Radiologic definitions of strictures have been developed for CTE and MRE; their reliability and responsiveness are being evaluated in index development programs. A comprehensive assessment strategy for strictures using IUS is needed. Aims To provide a detailed summary of definitions, diagnosis and monitoring of strictures on IUS as well as technical aspects of image acquisition. Methods We searched four databases up to 6 January 2024. Two‐stage screening was done in duplicate. We assessed risk of bias using QUADAS‐2. Results There were 56 studies eligible for inclusion. Definitions for strictures on IUS are heterogeneous, but the overall accuracy for diagnosis of strictures is high. The capability of IUS for characterising inflammation versus fibrosis in strictures is not accurate enough to be used in clinical practice or trials. We summarise definitions for improvement of strictures on IUS, and discuss parameters for image acquisition and standardisation. Conclusions This systematic review is the first step for a structured program to develop a stricture IUS index for CD.