Real-World Outcomes of Dual Advanced Therapy in Children and Young Adults with Inflammatory Bowel Disease.

BACKGROUND: Data are limited on the safety and efficacy of combining advanced therapies for refractory patients with IBD. AIM: To evaluate the real-world efficacy and safety of dual advanced therapy (DAT), combining 2 biologics or a biologic with a small molecule, in children and young adults with refractory IBD. METHODS: Primary outcome of this single IBD center cohort was DAT remission (clinical and biomarker remission) at first assessment (T1). Secondary outcomes included remission at T2, if DAT de-intensification (De-I) occurred and T3, if T2 DAT re-intensification (Re-I) occurred. Efficacy and safety outcomes were described. RESULTS: Of the 30 patients [43% female, 30% CD, median age of 18.3 [15.1-19.8] years], all 11 UST + TOFA achieved T1 remission; 6/10 De-I failed at T2; and 4/4 Re-I achieved T3 remission. Of 9 VDZ + TOFA, 6 achieved T1 remission; 5/6 De-I failed at T2; and 1/1 failed T3 Re-I. Of 4 UST + VDZ, 3 achieved T1 remission; 2/3 De-I failed at T2; and 0 had Re-I. Of 5 UST + UPA, 4 achieved T1 remission; 1/5 De-I failed at T2 but recaptured T3 remission post-Re-I. One VDZ + OZA achieved T1 remission and maintained T2 remission post-De-I to OZA monotherapy. At last follow-up, 43% were on original DAT, 17% on one of original DAT, and 40% neither. One UST + TOFA patient developed mild leukopenia and another developed septic arthritis and venous thromboembolism on VDZ + TOFA and prednisone. CONCLUSION: Most children and young adults treated with DAT achieved remission with minimal safety events; however, de-intensification had limited success.

Cytomegalovirus Colitis in a Patient with Severe Treatment Refractory Ulcerative Colitis.

Background: Cytomegalovirus (CMV) can be reactivated in ulcerative colitis (UC), but its role in progression of inflammation is unclear. Risk factors include severe colitis and treatment with immunosuppressive medications, particularly corticosteroids and immunomodulators. Methods: We report a case of cytomegalovirus colitis in a pediatric patient with pancolitis who had been refractory to aminosalicylate, infliximab, and ustekinumab and was in clinical remission and with transmural response on upadacitinib. Results: This is a case of a 13-year-old male with UC refractory to multiple therapies who were in clinical remission on upadacitinib 30 mg daily. He developed an acute increase in symptoms and did not respond to therapy escalation with increased upadacitinib 45 mg daily for 2 weeks and prednisone for 1 week. He was diagnosed with cytomegalovirus colitis on flexible sigmoidoscopy biopsy. He was treated with intravenous ganciclovir with tapering of immunosuppressive regimen. Despite initial response, he underwent subtotal colectomy and subsequent restorative proctocolectomy with ileal pouch anal-anastomosis. Conclusions: Despite our patient having multiple risk factors for developing CMV colitis, upadacitinib may have played a role when considering its known impact on the herpes family of viruses. CMV colitis should be evaluated for in any patient who presents with worsening symptoms without evidence of other infection or response to increase in therapy.

Crohn's disease.

Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract that might lead to progressive bowel damage and disability. The exact cause of Crohn's disease is unknown, but evidence points towards multifactorial events causing dysregulation of the innate immune system in genetically susceptible people. Commonly affecting the terminal ileum and proximal colon, Crohn's disease inflammation is often discontinuous and patchy, segmental, and transmural. Identification of characteristic findings on ileocolonoscopy and histology remains the diagnostic gold standard, but complete assessment involves laboratory abnormalities, including micronutrient deficiencies, cross-sectional imaging to identify transmural disease extent, severity and complications, and a psychosocial assessment. Treatment strategies for patients with Crohn's disease now go beyond achieving clinical remission to include deeper targets of endoscopic healing and consideration of adjunctive histological and transmural targets to alter disease progression potentially further. The use of early effective advanced therapies and development of therapies targeting alternative novel pathways with improved safety profiles have resulted in a new era of healing in Crohn's disease management. Future combination of advanced therapies with diet or other biological drugs and small molecules, together with improvements in tight control monitoring tools and predictive biomarkers might continue to improve outcomes for patients with Crohn's disease.

Effectiveness of Upadacitinib for Patients With Acute Severe Ulcerative Colitis: A Multicenter Experience.

INTRODUCTION: A significant proportion of patients with acute severe ulcerative colitis (ASUC) require colectomy. METHODS: Patients with ASUC treated with upadacitinib and intravenous corticosteroids at 5 hospitals are presented. The primary outcome was 90-day colectomy rate. Secondary outcomes included frequency of steroid-free clinical remission, adverse events, and all-cause readmissions. RESULTS: Of the 25 patients with ASUC treated with upadacitinib, 6 (24%) patients underwent colectomy, 15 (83%) of the 18 patients with available data and who did not undergo colectomy experienced steroid-free clinical remission (1 patient did not have complete data), 1 (4%) patient experienced a venous thromboembolic event, while 5 (20%) patients were readmitted. DISCUSSION: Upadacitinib along with intravenous corticosteroids may be an effective treatment for ASUC.

Determining the Accuracy of Intestinal Ultrasound Scores as a Prescreening Tool in Crohn's Disease Clinical Trials.

INTRODUCTION: High rates of screen failure for the minimum Simple Endoscopic Score for Crohn's Disease (SES-CD) plague Crohn's disease (CD) clinical trials. We aimed to determine the accuracy of segmental intestinal ultrasound (IUS) parameters and scores to detect segmental SES-CD activity. METHODS: A single-center, blinded, cross-sectional cohort study of children and young adult patients with CD undergoing IUS and ileocolonoscopy, comparing segmental IUS bowel wall thickness (BWT), hyperemia (modified Limberg score [MLS]), and scores to detect segmental SES-CD activity: (i) SES-CD ≤2, (ii) SES-CD ≥6, and (iii) SES-CD ≥4 in the terminal ileum (TI) only. Primary outcome was accuracy of BWT, MLS, and IUS scores to detect SES-CD ≤2 and SES-CD ≥6. Secondary outcomes were accuracy of TI BWT, MLS, and IUS scores to detect SES-CD ≥4 and correlation with the SES-CD. RESULTS: Eighty-two patients (median [interquartile range] age 16.5 [12.9-20.0] years) underwent IUS and ileocolonoscopy of 323 bowel segments. Segmental BWT ≤3.1 mm had a similar high accuracy to detect SES-CD ≤2 as IUS scores (area under the receiver operating curve [AUROC] 0.833 [95% confidence interval 0.76-0.91], 94% sensitivity, and 73% specificity). Segmental BWT ≥3.6 mm and ≥4.3 mm had similar high accuracy to detect SES-CD ≥6 (AUROC 0.950 [95% confidence interval 0.92-0.98], 89% sensitivity, 93% specificity) in the colon and an SES-CD ≥4 in the TI (AUROC 0.874 [0.79-0.96], 80% sensitivity, and 91% specificity) as IUS scores. Segmental IUS scores strongly correlated with the SES-CD. DISCUSSION: Segmental IUS BWT is highly accurate to detect moderate-to-severe endoscopic inflammation. IUS may be the ideal prescreening tool to reduce unnecessary trial screen failures.

Role of artificial intelligence in imaging and endoscopy for the diagnosis, monitoring and prognostication of inflammatory bowel disease: a scoping review protocol.

INTRODUCTION: Inflammatory bowel diseases (IBD) are immune-mediated conditions that are increasing in incidence and prevalence worldwide. Their assessment and monitoring are becoming increasingly important, though complex. The best disease control is achieved through tight monitoring of objective inflammatory parameters (such as serum and stool inflammatory markers), cross-sectional imaging and endoscopic assessment. Considering the complexity of the information obtained throughout a patient's journey, artificial intelligence (AI) provides an ideal adjunct to existing tools to help diagnose, monitor and predict the course of disease of patients with IBD. Therefore, we propose a scoping review assessing AI's role in diagnosis, monitoring and prognostication tools in patients with IBD. We aim to detect gaps in the literature and address them in future research endeavours. METHODS AND ANALYSIS: We will search electronic databases, including Medline, Embase, Cochrane CENTRAL, CINAHL Complete, Web of Science and IEEE Xplore. Two reviewers will independently screen the abstracts and titles first and then perform the full-text review. A third reviewer will resolve any conflict. We will include both observational studies and clinical trials. Study characteristics will be extracted using a data extraction form. The extracted data will be summarised in a tabular format, following the imaging modality theme and the study outcome assessed. The results will have an accompanying narrative review. ETHICS AND DISSEMINATION: Considering the nature of the project, ethical review by an institutional review board is not required. The data will be presented at academic conferences, and the final product will be published in a peer-reviewed journal.

Early Intestinal Ultrasound Response to Biologic Therapy Predicts Endoscopic Remission in Children with Ileal Crohn's Disease: Results from the Prospective Super Sonic Study.

BACKGROUND AND AIMS: STRIDE-II recommends early biomarker targets for treatment optimization to achieve treat-to-target (T2T) endoscopic remission (ER) in Crohn's disease (CD). Predictive capabilities of intestinal ultrasound (IUS) for T2T ER remains unknown. We aimed to evaluate IUS response to predict ER in children with CD. METHODS: Prospective longitudinal cohort study of children with ileal (TI) CD initiating biologic therapy undergoing IUS, clinical disease activity, and C-reactive protein (CRP) assessments at baseline, week 8, 6 months, and T2T within 1 year. Primary outcome was the accuracy of optimal cut-points to predict TI ER (SES-CD < 2) for change in bowel wall thickness (BWT) on IUS from baseline to week 8, and BWT at week 8. Area under the receiver operating curve analysis was performed and univariate analysis tested associations. RESULTS: 44 children (median age 13 [IQR 12-17] years, 29 (66%) biologic naïve) were included, 29 (66%) achieved ER. A > 18% decrease in TI BWT at week 8 predicted ER with an AUROC of 0.99 [95% CI 0.98-1.00], 100% sensitivity, 93% specificity, 97% PPV, and 100% NPV, superior to a > 46% decrease in PCDAI (AUROC 0.67 [95% CI 0.49-0.84]) and > 84% decrease in CRP (AUROC 0.49 [95% CI 0.31-0.67]) at week 8. CONCLUSIONS: Early change in TI BWT on IUS is highly predictive of ER in children with CD and superior to symptoms and CRP. Our findings suggest that IUS could be used for treatment optimization and tight control to guide T2T strategy.

Single-center Experience With Upadacitinib for Adolescents With Refractory Inflammatory Bowel Disease.

BACKGROUND: Upadacitinib (UPA) is a novel selective JAK inhibitor approved for adults with ulcerative colitis (UC) and with positive phase 3 data for Crohn's disease (CD). Pediatric off-label use is common due to delays in pediatric approvals; real-world data on UPA are needed to understand the safety and effectiveness in pediatric IBD. METHODS: This is a single-center retrospective case series study of adolescents (12-17 years) with inflammatory bowel disease IBD on UPA. The primary outcome was postinduction steroid-free clinical remission (SF-CR) defined as Pediatric UC Activity Index (PUCAI) or Pediatric CD Activity Index (PCDAI) ≤10. Secondary outcomes include postinduction clinical response (decrease ≥12.5 in PUCAI/PCDAI), postinduction C-reactive protein (CRP) normalization, 6-month SF-CR, and intestinal ultrasound response and remission. Adverse events were recorded through last follow-up. RESULTS: Twenty patients (9 CD, 10 UC, 1 IBD-U; 55% female; median age 15 years, 90% ≥2 biologics) were treated with UPA for ≥12 weeks (median 51 [43-63] weeks). Upadacitinib was used as monotherapy in 55% and as combination with ustekinumab and vedolizumab in 35% and 10%, respectively. Week 12 SF-CR was achieved in 75% (15/20) and 80% (16/20) with CRP normalization. About 3/4 (14/19) achieved SF-CR at 6 months. Adverse event occurred in 2 patients (10%): Cytomegalovirus colitis requiring hospitalization and hyperlipidemia requiring no treatment. In the 75% with ultrasound monitoring, response and remission were achieved in 77% and 60%, respectively. CONCLUSION: While awaiting pediatric registration trials, our data suggest that UPA is effective in inducing and maintaining SF-CR in adolescents with highly-refractory IBD with an acceptable safety profile.

This case series presents novel data on the effectiveness and safety of upadacitinib in adolescent patients with IBD.

Current and Novel Uses of Intestinal Ultrasound in Inflammatory Bowel Disease.

Intestinal ultrasound (IUS) is a patient-centric, noninvasive, real-time, point-of-care tool with the capability to aid in diagnosis and monitoring of disease activity in both Crohn's disease and ulcerative colitis without the need for bowel preparation. IUS can be used as a tool for precision monitoring of inflammatory bowel disease (IBD) treatment response. IUS as a cross-sectional imaging tool is as accurate as magnetic resonance enterography (MRE) for assessing the ileum and is more accurate than MRE for colonic assessment proximal to the rectum. Multiple simple ultrasound-based scoring systems have been internally validated with endoscopy in both Crohn's disease and ulcerative colitis, and changes in IUS parameters can be seen as early as 2 weeks after treatment initiation. IUS also plays a unique role in IBD activity monitoring of patients in whom avoidance of invasive testing is paramount, such as children and pregnant patients. Novel uses go beyond monitoring activity, with potential use of elastography to measure bowel wall stiffness to detect fibrosis and bowel damage for enhanced decision-making. Ultimately, IUS is likely to expand in the United States, facilitated by accessible expert training, access to equipment, and the development of a reimbursement model. This article provides a comprehensive review of the current and novel uses of IUS in IBD.

The Arrival of Intestinal Ultrasound for Inflammatory Bowel Disease Care in the United States.

Intestinal ultrasound (IUS) is a noninvasive and highly reliable point-of-care tool to evaluate inflammation of the bowel. It offers comparable accuracy to endoscopy and magnetic resonance enterography. Although IUS has been incorporated into the management of inflammatory bowel disease (IBD) in other parts of the world, it has only recently arrived in the United States. However, barriers to integration of IUS into IBD care in the United States have included a lack of adoption by leading centers, lack of educational opportunities, and an unclear path for remuneration. This article provides information about the use of IUS in IBD, reviews the data comparing existing modalities of assessment of IBD with IUS, and summarizes strategies to overcome existing barriers to IUS implementation, including the newly available US-based training pathway and appropriate billing practice.

Point-of-Care Intestinal Ultrasound in Pediatric Inflammatory Bowel Disease.

PURPOSE OF REVIEW: Intestinal ultrasound (IUS) is an emerging non-invasive point-of-care tool utilized by pediatric gastroenterologists for accurately detecting and monitoring inflammatory bowel disease (IBD) activity. In this article, we reviewed the evidence supporting and technique to perform IUS for children with IBD. RECENT FINDINGS: IUS technique can visualize the colon from the distal sigmoid until the cecum and the terminal ileum without the need for bowel preparation, fasting, or sedation in children with IBD. IUS has been shown to be accurate to endoscopy in children with ulcerative colitis and Crohn's disease. IUS may be the most accurate biomarker to follow as a marker of treatment response that is predictive of endoscopic outcomes in children with IBD. Multiple studies have demonstrated that IUS can be performed at the point-of-care for IBD activity assessment in children. Recent studies have demonstrated the accuracy of IUS to endoscopy and magnetic resonance enterography with an ability to be repeated as a monitor of treatment response for tight control monitoring.

The Role of Noninvasive Surrogates of Inflammation in Monitoring Pediatric Inflammatory Bowel Diseases: The Old and the New.

Effectiveness of limited available therapies for pediatric inflammatory bowel disease has reached stagnation. Previous non-invasive monitoring strategies have relied upon cumbersome tools to evaluate clinical symptoms and biochemical markers that do not reflect endoscopic activity or respond quickly to treatments. Novel, patient-centric, and highly accurate, monitoring strategies with a focus on intestinal ultrasound for a direct, precise monitoring of activity to achieve disease modification are now possible. Ultimately, research on the optimal tight control monitoring strategies, individualized to each pediatric inflammatory bowel disease patient, are in development and offer a hope to potential therapeutic ceiling breakthrough on the horizon.

Intestinal ultrasound as a non-invasive tool to monitor inflammatory bowel disease activity and guide clinical decision making.

Intestinal ultrasound (IUS) is a non-invasive, real-time, cross-sectional imaging tool that can be used at the point-of-care to assess disease activity in patients with Crohn's disease or ulcerative colitis. IUS promotes quick and impactful treatment decisions that can modify disease progression and enhance patient compliance. This review will summarize the technical aspects of IUS, the evidence to support the use of IUS in disease activity monitoring, the comparison of IUS to current standard of care monitoring modalities such as colonoscopy and calprotectin, and the optimal positioning of IUS in a tight-control monitoring strategy.

Crohn's Disease Patient Experiences and Preferences With Disease Monitoring: An International Qualitative Study.

Background: Strategies incorporating objective disease monitoring in Crohn's disease (CD), beyond clinical symptoms are important to improve patient outcomes. Little evidence exists to explore patient understanding of CD treatment goals, nor preferences and experiences with monitoring options. This qualitative study aimed to explore patient experiences and preferences of CD monitoring to inform monitoring strategies, improve patient engagement, and optimize a patient-centered approach to care. Methods: This study used a patient-oriented, qualitative descriptive design. Convenience and snowball sampling were used to recruit adult participants diagnosed with CD who had experience with at least 2 types of disease monitoring. Online focus groups were conducted and data were analyzed using thematic analysis. Results: This international study included 37 participants from Australia, Canada, United Kingdom, and the United States. Overall, participants preferred more noninvasive types of monitoring [eg, intestinal ultrasound (IUS)] but were willing to undergo more invasive monitoring (eg, colonoscopy) if required. To improve disease monitoring, participants wanted increased access to IUS, establishment of a patient-centered interdisciplinary team and access to information and self-testing. Participants identified challenges with communication between patients and providers and stressed the importance of participating in shared decision making and being equal team members in their care. Conclusions: It is imperative to incorporate patient-driven preferences into how we can best structure monitoring strategies, to ensure equitable access to those preferred modalities and embrace a shared decision-making approach to disease management in CD.

Intestinal Ultrasound for the Pediatric Gastroenterologist: A Guide for Inflammatory Bowel Disease Monitoring in Children: Expert Consensus on Behalf of the International Bowel Ultrasound Group (IBUS) Pediatric Committee.

Crohn disease and ulcerative colitis are chronic inflammatory bowel diseases (IBD) often diagnosed in childhood. A strict monitoring strategy can potentially alter the disease course and facilitate early effective treatment before irreversible bowel damage occurs. Serial colonoscopy in children, the gold standard for monitoring, is impractical. Accurate, real-time, noninvasive markers of disease activity are needed. Intestinal ultrasound is an accurate, noninvasive, real-time, point-of-care, cross-sectional imaging tool used to monitor inflammation in pediatric IBD patients in Europe, Canada, and Australia. It is now emerging in a few expert centers in the United States as a safe, non-radiating, inexpensive, bedside tool used by the treating gastroenterologist for real-time decision-making. Unlike the standard biomarkers of pediatric IBD activity, C-reactive protein, and fecal calprotectin, intestinal ultrasound (IUS) facilitates disease localization, characterizes severity, extent, and accurately detects complications. Perhaps most importantly, IUS may enhance shared understanding and ease the burden of treatment decision-making for both the gastroenterologist and the patient. There is a lack of standardization for bedside IUS among pediatric gastroenterologists. The purpose is to outline a standardized approach to pediatric bedside IUS, including basic equipment requirements and technique, patient selection, preparation and positioning, technical considerations and limitations, documentation of mesenteric and luminal features of IBD, characterization of penetrating disease and strictures, and provide a proposed pediatric IUS monitoring algorithm to guide care.

A Single-Center Experience with Dupilumab for Atopic or Psoriasiform Dermatitis in Patients with Inflammatory Bowel Disease.

INTRODUCTION: Dupilumab blocks IL4/IL13 and is used in atopic disease. There are concerns that blockade may lead to inflammatory bowel disease (IBD) inception or activity. Limited data exist on the use of this therapy in patients with IBD; we aimed to describe our experience using dupilumab in IBD to treat concomitant atopic dermatitis (AD) or anti-TNF-induced dermatitis. METHODS: We analyzed the electronic medical records (2018-2022) in a single, tertiary care center to identify patients with IBD on dupilumab. Clinical and demographic data were gathered, including disease location/behavior, personal/family history of atopy, indication for and response to dupilumab, IBD medication history, and adverse events. RESULTS: Seventeen patients (65% Crohn's) were identified with IBD on dupilumab for dermatitis; 9 for severe AD and 8 for a worsened dermatitis, either AD or psoriasiform dermatitis (PD), induced by anti-TNF. They were treated for a median 1.2 [IQR 0.6-2.3] years. All patients had a dermatologic response to dupilumab and remained on dupilumab at last follow-up. No adverse events were identified, including no increase in IBD activity. In those with dermatitis worsened or induced by anti-TNF, all started dupilumab in combination with another biologic: 3 with anti-TNF, 4 with ustekinumab, and 1 with vedolizumab. Seven of the eight had a response to the initial combination of biologics; however, one patient using dupilumab-anti-TNF ultimately changed to combination dupilumab-ustekinumab to achieve resolution of the dermatitis. CONCLUSION: Dupilumab is safe and effective for dermatitis in patients with IBD, both primary atopic dermatitis and dermatitis induced or worsened by anti-TNF.