Bedside Intestinal Ultrasound Performed in an Inflammatory Bowel Disease Urgent Assessment Clinic Improves Clinical Decision-Making and Resource Utilization.

Background: Patients with inflammatory bowel disease (IBD) require accessible, timely, and noninvasive strategies to monitor disease. The aim was to assess the integration of intestinal ultrasound (IUS) on decision-making and endoscopy utilization in a standardized care pathway. Methods: This prospective, multicenter, international, observational cohort study included patients seen within a centralized model for IBD care was conducted during the COVID pandemic. Patients were evaluated with IUS alone or in combination with an in-clinic, unsedated sigmoidoscopy. Demographic, clinical, laboratory, and imaging data, clinical decisions, and need for urgent endoscopy, hospitalization, and surgeries were recorded. Results: Of the 158 patients included, the majority had an established diagnosis of Crohn's disease (n = 123, 78%), and 47% (n = 75) of patients were on biologic therapy. IUS identified active inflammation in 65% (n = 102) of patients, and strictures in 14% (n = 22). Fecal calprotectin levels correlated with inflammation detected on IUS (median of 50 µg/g [Q1-Q3: 26-107 µg/g] without inflammation and 270 µg/g [Q1-Q3: 61-556 µg/g] with inflammation; p = 0.0271). In the majority of patients, clinical assessment with IUS led to an acute change in IBD-specific medications (57%, n = 90) and avoided or delayed the need for urgent endoscopy (85%, n = 134). Four patients were referred for urgent surgical consultation. Conclusions: Point-of-care IUS used in a flare clinic pathway is a useful strategy to improve effective IBD care delivery and to assist in therapeutic management decisions, in many cases avoiding the acute need for endoscopy.

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.

Infliximab Trough Levels Are Associated With Transmural Sonographic Healing in Inflammatory Bowel Disease.

BACKGROUND: Mucosal healing improves clinical outcomes in patients with inflammatory bowel disease (IBD) and is associated with higher infliximab trough levels (ITLs). Transmural healing, assessed by intestinal ultrasound (IUS), is emerging as an objective target in Crohn's disease (CD) and ulcerative colitis (UC). This study explores the correlation between maintenance ITLs and sonographic transmural healing. METHODS: Patients on maintenance infliximab therapy were prospectively enrolled to undergo paired IUS examination and serum ITL. Infliximab trough levels were compared between patients with and without sonographic markers of inflammation using the Mann-Whitney U test. RESULTS: A prospective cohort of 103 patients (51% male; 79 CD; 24 UC; median duration of disease 8 years) underwent IUS and serum ITL testing. Forty-one percent of CD and 66% of UC patients demonstrated sonographic healing (bowel wall thickening ≤3 mm with no increase in color Doppler signal). Crohn's disease patients with sonographic healing had higher median ITL compared with those with sonographic inflammation (4.8 µg/mL vs 3.1 µg/mL; P = .049). Additionally, the presence of hyperemia on Doppler was independently associated with lower ITL compared with those without hyperemia (2.1 µg/mL vs 4.2 µg/mL, respectively; P = .003). There was no significant association between ITL and other sonographic markers of inflammation. In UC, lower ITL was associated with hyperemia on Doppler imaging (P = .04). There was no association between ITL and sonographic healing or any other individual sonographic parameter of inflammation. CONCLUSIONS: Lower maintenance infliximab levels are associated with sonographic parameters of inflammation in UC and CD. Further studies are needed to determine whether targeting higher infliximab levels can increase sonographic healing.

Transmural healing assessed by intestinal ultrasound allows for objective assessment of disease activity. Lower maintenance infliximab levels were associated with sonographic parameters of inflammation in IBD. Further studies are needed to determine whether targeting higher infliximab levels can increase sonographic healing.

Treat to transmural healing: how to incorporate intestinal ultrasound into the treatment of inflammatory bowel disease.

Intestinal ultrasound (IUS) is emerging as a key tool to achieving the therapeutic target of transmural healing in inflammatory bowel disease (IBD). IUS is a non-invasive, radiation-free, imaging modality comparable to MRI, CT and ileocolonoscopy (IC). With the appropriate training and equipment, IUS can be an easily repeatable bedside test for IBD diagnosis and disease monitoring, including treatment response. Core to successful high quality IUS employment are appropriate training and expert techniques; however, the training pathway will not be explored in this review. Given the increasing shift towards objective assessment for tight disease control, gastroenterologist-led IUS should be incorporated into the armamentarium of imaging modalities alongside radiologists, to enhance our diagnostic and monitoring toolbox. This comprehensive review aims to outline the current literature around IUS and propose the placement of IUS in a treat-to-target algorithm in IBD. Ultimately, IUS facilitates timely management decisions to optimise patient care with potential to revolutionise patient outcomes, moving towards transmural healing as the holy grail of therapy in IBD.

Toward transmural healing: Sonographic healing is associated with improved long-term outcomes in patients with Crohn's disease.

BACKGROUND AND AIMS: Transmural healing has emerged as a treatment target in Crohn's disease (CD). We investigated whether transmural healing assessed with intestinal ultrasound (IUS) is associated with improved clinical outcomes in patients with CD in clinical remission. METHODS: Patients with CD in clinical remission at baseline (HBI <4) having IUS between August 2017 and June 2020 with at least 6-months' follow-up were retrospectively studied. Time to medication escalation, corticosteroid use and CD-related hospitalisation or surgery were compared by the presence or absence of sonographic healing, defined as bowel wall thickness ≤3 mm without hyperemia on color Doppler, inflammatory fat, or disrupted bowel wall stratification. Factors associated with survival were analyzed by Kaplan-Meier analysis using Cox proportional-hazard model. RESULTS: Of 202 consecutive patients (50% male), sonographic inflammation was present in 61%. During median follow-up of 19 (IQR 13-27) months, medication escalation occurred in 52%, corticosteroid use in 23%, hospitalisation in 21%, and CD-related surgery in 13%. Sonographic healing was significantly associated with a reduced risk of medication escalation (p = 0.0018), corticosteroid use (p = 0.0247), hospitalisation (p = 0.0102), and surgery (p = 0.083). On multivariable analysis, sonographic healing was significantly associated with an increased odds of medication escalation-free survival (hazard ratio [HR]:1.94; 95% CI 1.23-3.06; p = 0.004) and corticosteroid-free survival (HR:2.41; 95% CI 1.24-4.67; p = 0.009), but not with hospitalisation or surgery. CONCLUSION: In patients with CD in clinical remission, sonographic healing is associated with improved clinical outcomes. Further studies are needed to determine whether sonographic healing should be a treatment target.

Review article: investigation and management of internal fistulae in Crohn's disease.

BACKGROUND: Crohn's disease is an inflammatory, penetrating intestinal disease associated with fistula formation. Fistulae in Crohn's disease can be classified into external and internal fistulae. Internal fistulae form between the gastrointestinal tract and another internal organ and include enteroenteric, enterocolic, enterovesical and rectovaginal fistulae. They are associated with significant morbidity and a decreased quality of life. AIM: To review the classification, diagnosis, medical and surgical management of internal fistulae in Crohn's disease, and propose a treatment algorithm. METHODS: A literature review on internal fistulae in Crohn's disease in the adult population was undertaken, synthesised and summarised. RESULTS: Internal fistulae occur in up to 15% of patients with Crohn's disease. Multi-modal assessment including a combination of endoscopy and cross-sectional imaging, usually magnetic resonance, is required to diagnose fistulae and determine extent of disease. Determining optimal treatment strategies for these complex fistulae remains a challenge due to limited and generally low-quality data. Most studies to date have focussed on luminal disease, with (usually post hoc) outcomes more often reported for external fistulae, particularly perianal fistulae, than internal fistulae. Anti-tumour necrosis factor therapies have emerged as the mainstay of medical therapy, with particularly promising data for enterovesical fistulae, but many patients will still require surgical intervention. The indications and optimal timing of surgery vs medical therapy remains uncertain; thus multi-disciplinary input when making such decisions is important. CONCLUSIONS: Internal fistulae result in significantly increased morbidity in Crohn's disease, and further studies to determine optimal multi-modality management strategies incorporating medical and surgical therapy are required.

Expert Consensus on Optimal Acquisition and Development of the International Bowel Ultrasound Segmental Activity Score [IBUS-SAS]: A Reliability and Inter-rater Variability Study on Intestinal Ultrasonography in Crohn's Disease.

BACKGROUND AND AIMS: Intestinal ultrasound [IUS] is an accurate, patient-centreed monitoring tool that objectively evaluates Crohn's disease [CD] activity. However no current, widely accepted, reproducible activity index exists to facilitate consistent IUS identification of inflammatory activity. The aim of this study is to identify key parameters of CD inflammation on IUS, evaluate their reliability, and develop an IUS index reflecting segmental activity. METHODS: There were three phases: [1] expert consensus Delphi method to derive measures of IUS activity; [2] an initial, multi-expert case acquisition and expert interpretation of 20 blinded cases, to measure inter-rater reliability for individual measures; [3] refinement of case acquisition and interpretation by 12 international experts, with 30 blinded case reads with reliability assessment and development of a segmental activity score. RESULTS: Delphi consensus: 11 experts representing seven countries identified four key parameters including: [1] bowel wall thickness [BWT]; [2] bowel wall stratification; [3] hyperaemia of the wall [colour Doppler imaging]; and [4] inflammatory mesenteric fat. Blind read: each variable exhibited moderate to substantial reliability. Optimal, standardised image and cineloop acquisition were established. Second blind read and score development: intra-class correlation coefficient [ICC] for BWT was almost perfect at 0.96 [0.94-0.98]. All four parameters correlated with the global disease activity assessment and were included in the final International Bowel Ultrasound Segmental Activity Score with almost perfect ICC (0.97 [0.95-0.99, p <0.001]). CONCLUSIONS: Using expert consensus and standardised approaches, identification of key activity measurements on IUS has been achieved and a segmental activity score has been proposed, demonstrating excellent reliability.