Systematic review: Defining, diagnosing and monitoring small bowel strictures in Crohn's disease on intestinal ultrasound.

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.

Submucosal Injection of the RNA Oligonucleotide GUT-1 in Active Ulcerative Colitis Patients: A Randomized, Double-Blind, Placebo-Controlled Phase 2a Induction Trial.

BACKGROUND AND AIMS: Carbohydrate sulfotransferase 15 [CHST15] biosynthesizes sulphated matrix glycosaminoglycans and is implicated in intestinal inflammation and fibrosis. Here, we evaluate the efficacy and safety of the double-stranded RNA oligonucleotide GUT-1, a specific blocker of CHST15, as induction therapy in patients with ulcerative colitis [UC]. METHODS: In this randomized, double-blind, placebo-controlled, phase 2a study, we enrolled endoscopically active UC patients, refractory to conventional therapy, in five hospital centres across Germany. Patients were randomized 1:1:1 using a block randomized technique to receive a single dosing of 25 nM GUT-1, 250 nM GUT-1, or placebo by endoscopic submucosal injections. The primary outcome measure was improvement of endoscopic lesions at weeks 2 or 4. The secondary outcome measures included clinical and histological responses. Safety was assessed in all patients who received treatment. RESULTS: Twenty-eight patients were screened, 24 were randomized, and 21 were evaluated. Endoscopic improvement at weeks 2 or 4 was achieved by 71.4% in the GUT-1 250 nM, 0% in the GUT-1 25 nM, and 28.6% in the placebo group. Clinical remission was shown by 57.1% in the GUT-1 250 nM, 0% in the GUT-1 25 nM, and 14.3% in the placebo groups. Histological improvement was shown by 42.9% in the GUT-1 250 nM, 0% in the GUT-1 25 nM, and 0% in the placebo groups. GUT-1 250 nM reduced CHST15 expression significantly and suppressed mucosal inflammation and fibrosis. GUT-1 application was well tolerated. CONCLUSION: Single dosing by submucosal injection of GUT-1 repressed CHST15 mucosal expression and may represent a novel induction therapy by modulating tissue remodelling in UC.

Intestinal MRI in Inflammatory Bowel Disease - Literature and Survey-Based Recommendations regarding Reporting by the German Radiological Society (DRG) and the German Competence Network for Inflammatory Bowel Diseases. / Intestinale MRT bei chronisch-entzündlichen Darmerkrankungen ­ Literatur- und umfragebasierte Empfehlungen zur Befundung durch die AG Gastrointestinal-/Abdominaldiagnostik der DRG und der AG Bildgebung des Kompetenznetz Darmerkrankungen.

BACKGROUND: MR-enterography/enteroclysis (MRE) is increasingly used for primary diagnosis, detection of complications, and monitoring of patients with inflammatory bowel disease (IBD). Standardization of reporting is relevant to ensure quality of the methodology and to improve communication between different faculties. The current manuscript describes the features that are required for optimized reporting of MRE in IBD. METHODS: An expert consensus panel of radiologists and gastroenterologists conducted a systematic search of the literature. In a Delphi process, members of the German Radiological Society (DRG) and members of the Competence Network for Inflammatory Bowel Diseases voted on relevant criteria for the reporting of findings in MRE. Based on the voting results, statements were developed by the expert consensus panel. RESULTS: Clinically relevant aspects of MRE findings have been defined to optimize reporting and to standardize terminology. Minimal requirements for standardized reporting are suggested. The statements focus on the description of disease activity as well as on complications of IBD. Attributes of intestinal inflammation are described and illustrated by exemplary images. CONCLUSION: The current manuscript provides standardized parameters and gives practical recommendations on how to report and how to characterize MRE findings in patients with IBD. KEY POINTS: · Systematic overview provides practice-oriented recommendations and names and evaluates the decisive criteria for reporting and interpretation of MRI in inflammatory bowel disease.. · Standardized terminology and reporting criteria for MRI in IBD improves interdisciplinary communication.. · Standardized collection and documentation of MRI findings in IBD helps to further establish the method and to improve care for IBD patients.. CITATION FORMAT: · Wessling J, Kucharzik T, Bettenworth D et al. Intestinal MRI in Inflammatory Bowel Disease - Literature and Survey-Based Recommendations regarding Reporting by the German Radiological Society (DRG) and the German Competence Network for Inflammatory Bowel Diseases. Fortschr Röntgenstr 2023; 195: 675 - 690.

Early Ultrasound Response and Progressive Transmural Remission After Treatment With Ustekinumab in Crohn's Disease.

BACKGROUND & AIMS: In this STARDUST substudy, the effect of ustekinumab on transmural bowel inflammation was assessed in adults with moderate-to-severe Crohn's disease (CD) by using intestinal ultrasound (IUS), a noninvasive imaging procedure. METHODS: STARDUST was an international, multicenter, phase 3b, interventional, randomized controlled trial specifically designed to compare treat-to-target and standard-of-care treatment strategies in ustekinumab-treated CD patients. In this substudy, the most affected bowel segment at baseline by IUS was used for all analyses. Key IUS endpoints (centrally read, parameter-blinded) were IUS response, transmural remission, bowel wall thickness (BWT), blood flow, bowel wall stratification, and inflammatory fat. RESULTS: Seventy-seven patients were evaluated. IUS response could be determined 4 weeks after treatment initiation, with progressive improvement through week 48. IUS response and transmural remission rates at week 48 were 46.3% and 24.1%, respectively. IUS response, transmural remission, BWT, and blood flow normalization rates were more pronounced in the colon and biologic-naive patients. Fair/moderate reliability (κ = 0.21-0.51) was observed between week 4 IUS response and week 48 overall endoscopic response and fecal calprotectin/complete biomarker outcomes. Endoscopy and IUS baseline agreement was >90% in determining the terminal ileum as the most affected bowel segment. IUS response absence at week 4 was associated with no endoscopic response (based on the simplified endoscopic score for Crohn's disease terminal ileum subscore) at week 48 (negative predictive value = 73%). CONCLUSIONS: In this first international, multicenter, interventional study, IUS showed that ustekinumab-treated CD patients achieved progressive IUS response (46.3%) and transmural remission (24.1%) through week 48, with a more robust response in the colon and biologic-naive patients. CLINICALTRIALS: gov number: NCT03107793.

Recent advances in clinical practice: advances in cross-sectional imaging in inflammatory bowel disease.

Endoscopy remains the reference standard for the diagnosis and assessment of patients with inflammatory bowel disease (IBD), but it has several important limitations. Cross-sectional imaging techniques such as magnetic resonance enterography (MRE) and intestinal ultrasound (IUS) are better tolerated and safer. Moreover, they can examine the entire bowel, even in patients with stenoses and/or severe inflammation. A variety of cross-sectional imaging activity scores strongly correlate with endoscopic measures of mucosal inflammation in the colon and terminal ileum. Unlike endoscopy, cross-sectional techniques allow complete visualisation of the small-bowel and assess for extraintestinal disease, which occurs in nearly half of patients with IBD. Extramural findings may predict outcomes better than endoscopic mucosal assessment, so cross-sectional techniques might help identify more relevant therapeutic targets. Coupled with their high sensitivity, these advantages have made MRE and IUS the primary non-invasive options for diagnosing and monitoring Crohn's disease; they are appropriate first-line investigations, and have become viable alternatives to colonoscopy. This review discusses cross-sectional imaging in IBD in current clinical practice as well as research lines that will define the future role of these techniques.

CORE-IBD: A Multidisciplinary International Consensus Initiative to Develop a Core Outcome Set for Randomized Controlled Trials in Inflammatory Bowel Disease.

BACKGROUND & AIMS: End points to determine the efficacy and safety of medical therapies for Crohn's disease (CD) and ulcerative colitis (UC) are evolving. Given the heterogeneity in current outcome measures, harmonizing end points in a core outcome set for randomized controlled trials is a priority for drug development in inflammatory bowel disease. METHODS: Candidate outcome domains and outcome measures were generated from systematic literature reviews and patient engagement surveys and interviews. An iterative Delphi process was conducted to establish consensus: panelists anonymously voted on items using a 9-point Likert scale, and feedback was incorporated between rounds to refine statements. Consensus meetings were held to ratify the outcome domains and core outcome measures. Stakeholders were recruited internationally, and included gastroenterologists, colorectal surgeons, methodologists, and clinical trialists. RESULTS: A total of 235 patients and 53 experts participated. Patient-reported outcomes, quality of life, endoscopy, biomarkers, and safety were considered core domains; histopathology was an additional domain for UC. In CD, there was consensus to use the 2-item patient-reported outcome (ie, abdominal pain and stool frequency), Crohn's Disease Activity Index, Simple Endoscopic Score for Crohn's Disease, C-reactive protein, fecal calprotectin, and co-primary end points of symptomatic remission and endoscopic response. In UC, there was consensus to use the 9-point Mayo Clinic Score, fecal urgency, Robarts Histopathology Index or Geboes Score, fecal calprotectin, and a composite primary end point including both symptomatic and endoscopic remission. Safety outcomes should be reported using the Medical Dictionary for Regulatory Activities. CONCLUSIONS: This multidisciplinary collaboration involving patients and clinical experts has produced the first core outcome set that can be applied to randomized controlled trials of CD and UC.

[Position paper on reporting of intestinal ultrasound findings in patients with inflammatory bowel disease]. / Positionspapier zur Befunderhebung von Darmultraschallbefunden bei chronisch entzündlichen Darmerkrankungen.

BACKGROUND: Intestinal ultrasound is increasingly used for primary diagnosis, detection of complications and monitoring of patients with Crohn's disease and ulcerative colitis. Standardization of reporting is relevant to ensure quality of the methodology and to improve communication between different specialties. The current manuscript describes the features required for optimized reporting of intestinal ultrasound findings in inflammatory bowel disease (IBD). METHODS: An expert consensus panel of gastroenterologists, radiologists, pathologists, paediatric gastroenterologists and surgeons conducted a systematic literature search. In a Delphi- process members of the Kompetenznetz Darmerkrankungen in collaboration with members of the German Society for Radiology (DRG) voted on relevant criteria for reporting of findings in intestinal ultrasound. Based on the voting results statements were agreed by expert consensus. RESULTS: Clinically relevant aspects of intestinal ultrasound (IUS) findings have been defined to optimize reporting and to standardize terminology. Minimal requirements for standardized reporting are suggested. The statements focus on description of disease activity as well as on complications of IBD. Attributes of intestinal inflammation are described and illustrated by exemplary images. CONCLUSION: The current manuscript provides practical recommendations on how to standardize documentation and reporting from intestinal ultrasound findings in patients with IBD.

[Living guideline on ulcerative colitis]. / Living Guideline Colitis ulcerosa.

The treatment spectrum for ulcerative colitis has greatly increased in recent years. Mesalazine is still the standard drug treatment for uncomplicated ulcerative colitis in various forms of administration. Glucocorticoids are highly effective in the acute treatment of ulcerative colitis but should only be used on a short-term basis due to the pronounced side effects. For forms with a complicated course of ulcerative colitis, immunosuppressive and immunomodulating substances, such as azothioprine as well as various biologicals, Janus kinase inhibitors (JAKi), sphingosine-1-phosphate receptor agonists (S1PR agonists) and calcineurin inhibitors are available after failure of conventional treatment. A proctocolectomy should be considered in cases of a treatment-refractive course or with detection of carcinomas and high-grade epithelial dysplasia.

INSPECT: A Retrospective Study to Evaluate Long-term Effectiveness and Safety of Darvadstrocel in Patients With Perianal Fistulizing Crohn's Disease Treated in the ADMIRE-CD Trial.

BACKGROUND: The efficacy of a single administration of darvadstrocel (expanded allogeneic adipose-derived mesenchymal stem cells) for treating complex perianal fistulas in patients with Crohn's disease was demonstrated in a randomized, double-blind trial (ADMIRE-CD [Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulizing Crohn\'s Disease] trial). The current chart review study (INSPECT [A retrospectIve chart review study evaluatINg the longer-term effectiveneSs of darvadstrocel in PatiEnts who CompleTed ADMIRE-CD]) evaluated the longer-term effectiveness and safety of darvadstrocel. METHODS: Eligible patients had completed at least 52 weeks in the ADMIRE-CD trial. Data on clinical remission and fistula relapse outcomes were collected retrospectively at 104 and 156 weeks after treatment. Adverse events of special interest (tumorigenicity and ectopic tissue formation) were collected up to 208 weeks after treatment. RESULTS: Eighty-nine patients were included (43 darvadstrocel patients, 46 control subjects). At 52, 104, and 156 weeks posttreatment, clinical remission was observed in 29 (67.4%) of 43, 23 (53.5%) of 43, and 23 (53.5%) of 43 darvadstrocel-treated patients, compared with 24 (52.2%) of 46, 20 (43.5%) of 46, and 21 (45.7%) of 46 control subjects, respectively. In patients with clinical remission at week 52, this remission was sustained at 104 and 156 weeks after treatment in 19 (65.5%) of 29 and 16 (55.2%) of 29 darvadstrocel-treated patients and in 17 (70.8%) of 24 and 13 (54.2%) of 24 control subjects, respectively. Time to fistula relapse and incidence of fistula relapse or new fistula occurrence were not significantly different between groups. Tumorigenicity was reported for 1 (2.2%) patient in the control group (malignant epidermoid carcinoma). No ectopic tissue formation was reported. CONCLUSIONS: Real-world follow-up of patients from the ADMIRE-CD trial indicates that clinical remission of complex perianal fistulas can be sustained in the long term irrespective of whether it is achieved through darvadstrocel administration or maintenance treatment regimens and confirms a favorable long-term safety profile of darvadstrocel.

This retrospective chart review of patients treated with darvadstrocel indicates sustained remission and confirms a favorable safety profile up to 156 weeks after a single administration of stem cells for treatment of complex perianal fistulas in patients with Crohn's disease.

ECCO-ESGAR Topical Review on Optimizing Reporting for Cross-Sectional Imaging in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: The diagnosis and follow up of patients with inflammatory bowel disease [IBD] requires cross-sectional imaging modalities, such as intestinal ultrasound [IUS], magnetic resonance imaging [MRI] and computed tomography [CT]. The quality and homogeneity of medical reporting are crucial to ensure effective communication between specialists and to improve patient care. The current topical review addresses optimized reporting requirements for cross-sectional imaging in IBD. METHODS: An expert consensus panel consisting of gastroenterologists, radiologists and surgeons convened by the ECCO in collaboration with ESGAR performed a systematic literature review covering the reporting aspects of MRI, CT, IUS, endoanal ultrasonography and transperineal ultrasonography in IBD. Practice position statements were developed utilizing a Delphi methodology incorporating two consecutive rounds. Current practice positions were set when ≥80% of the participants agreed on a recommendation. RESULTS: Twenty-five practice positions were developed, establishing standard terminology for optimal reporting in cross-sectional imaging. Assessment of inflammation, complications and imaging of perianal CD are outlined. The minimum requirements of a standardized report, including a list of essential reporting items, have been defined. CONCLUSIONS: This topical review offers practice recommendations to optimize and homogenize reporting in cross-sectional imaging in IBD.

ECCO Guidelines on Therapeutics in Ulcerative Colitis: Surgical Treatment.

This is the second of a series of two articles reporting the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of adult patients with ulcerative colitis [UC]. The first article is focused on medical management, and the present article addresses medical treatment of acute severe ulcerative colitis [ASUC] and surgical management of medically refractory UC patients, including preoperative optimisation, surgical strategies, and technical issues. The article provides advice for a variety of common clinical and surgical conditions. Together, the articles represent an update of the evidence-based recommendations of the ECCO for UC.