Brighter days ahead: the shifting landscape of IBD therapy.

Inflammatory Bowel Disease Clinical

INTRODUCTION: Background & Purpose: Leaders in medical education strive to develop more interactive and efficacious teaching methods as preclinical teaching typically occurs in passive didactic lectures. The pathophysiology, diagnosis and treatment of diseases are explored in textbooks. However, the effect of disease on patients’ lives and the difficulty of managing chronic conditions are often not conveyed. Preclinical students would benefit from more patient interaction as patient care is the essence of being a physician. In this patient-centered educational panel, we focus on Inflammatory Bowel Disease (IBD). LEARNING OBJECTIVES: 1. Understand how IBD impacts patients’ lives 2. Expose students to the challenges of living with IBD from patient and caregiver perspective 3. Recognize how the Crohn’s & Colitis Foundation supports IBD patients 4. Review the role of a multidisciplinary approach in treating IBD patients and the potential role of complementary medicine METHODS: In 2017 and 2018, Albany Medical College incorporated an IBD patient panel into the preclinical gastrointestinal curriculum. Students (n = 140), having already been lectured on IBD, attended an interactive 2-hour panel in which patients, caregivers, physicians and the Crohn's & Colitis Foundation shared their experiences. Students then completed a Qualtrics survey. RESULTS: Student responses indicated that 96% strongly agreed/agreed that learning from patients helped to understand the complexity of managing a chronic disease, 89% strongly agreed/agreed that the patient panel supported traditional IBD lectures well and 94% strongly agreed/agreed that future students would benefit from a similar panel (Figure 1). Additionally, 73% strongly agreed/agreed that there is a role for complementary medicine (Figure 2). Student narratives suggested that the panel enriched their medical education (Figure 3). CONCLUSION: This panel showcased the challenges of diagnosing, managing and living with IBD. Learning about chronic disease from a patient encouraged future physicians to consider how the disease affects many aspects of one’s life. The panel challenged students to consider a role for complementary medicine in IBD. Survey responses found that the panel enhanced students’ understanding of IBD beyond what could be learned from traditional lectures and textbook readings. The success of this panel illustrates that patient-centered learning enriches preclinical education and should be incorporated in medical curriculum moving forward.

P152 ANALYSIS OF HUMAN COLONIC TISSUE AND PERIPHERAL BLOOD BY MASS CYTOMETRY REVEALS IMMUNE SIGNATURES DIFFERENTIATING INFLAMMATORY STATES IN UC, CD, AND CONTROLS

Multi-omic and multimodal datasets with detailed clinical annotations offer significant potential to advance our understanding of inflammatory bowel diseases (IBD), refine diagnostics, and enable personalized therapeutic strategies. In this multi-cohort study, we performed an extensive multi-omic and multimodal analysis of 1,002 clinically annotated patients with IBD and non-IBD controls, incorporating whole-exome and RNA sequencing of normal and inflamed gut tissues, serum proteomics, and histopathological assessments from images of H&E-stained tissue sections. Transcriptomic profiles of normal and inflamed tissues revealed distinct site-specific inflammatory signatures in Crohn's disease (CD) and ulcerative colitis (UC). Leveraging serum proteomics, we developed an inflammatory protein severity signature that reflects underlying intestinal molecular inflammation. Furthermore, foundation model-based deep learning accurately predicted histologic disease activity scores from images of H&Estained intestinal tissue sections, offering a robust tool for clinical evaluation. Our integrative analysis highlights the potential of combining multi-omics and advanced computational approaches to improve our understanding and management of IBD.

Multi-omic and multimodal datasets with detailed clinical annotations offer significant potential to advance our understanding of inflammatory bowel diseases (IBD), refine diagnostics, and enable personalized therapeutic strategies. In this multi-cohort study, we performed an extensive multi-omic and multimodal analysis of 1,002 clinically annotated patients with IBD and non-IBD controls, incorporating whole-exome and RNA sequencing of normal and inflamed gut tissues, serum proteomics, and histopathological assessments from images of H&E-stained tissue sections. Transcriptomic profiles of normal and inflamed tissues revealed distinct site-specific inflammatory signatures in Crohn’s disease (CD) and ulcerative colitis (UC). Leveraging serum proteomics, we developed an inflammatory protein severity signature that reflects underlying intestinal molecular inflammation. Furthermore, foundation model-based deep learning accurately predicted histologic disease activity scores from images of H&E-stained intestinal tissue sections, offering a robust tool for clinical evaluation. Our integrative analysis highlights the potential of combining multi-omics and advanced computational approaches to improve our understanding and management of IBD.

P620 Differences in illness perceptions of Inflammatory Bowel Disease (IBD) between Healthcare Practitioners (HCPs) and patients in a UK tertiary IBD centre

The anatomic pathology of inflammatory bowel disease (IBD) is necessarily studied and continually evaluated for better understanding of its scope and meaningful classification. The reasoning behind classification is to enable grouping of ailments for reliable treatment and prognostication. The two prominent IBD are traditionally subclassified as ulcerative colitis (UC) and Crohn's disease (CD). They are separated from most other IBD by two features: (1) their idiopathic nature and (2) their chronicity. Superb descriptions of their anatomic manifestations abound in literature and their salient features can be found in selected articles and specialty texts [1-12]. Despite the apparent redundancy, some of this chapter will be devoted to the traditional descriptions. During much of the past century many inflammatory diseases of the alimentary tract have been subclassified and to a considerable degree great insight into pathogenesis has been gained [13-18]. This is particularly true for infectious gastroenterocolitides, food intolerance, and to some extent iatrogenic injury (such as radiation or drug effects). What remains are a number of idiopathic inflammatory diseases, the dominant ones being UC and CD. It is the responsibility of our generation and future ones to continue the progression and place our new understanding of IBD in the context of modern understanding of biology and medicine. With this in mind, even the traditional practice of gross examination and microscopic study can contribute to 21st-century understanding of IBD. The anatomic pathologic findings in IBD can be separated into those estabUshed traditional findings, and those that are more modern based on relatively recent descriptions. Interestingly, some of the modern anatomic pathological interpretations may have their root in our modern treatment and diagnostic techniques which are unmasking previously under-recognized elements of IBD. Of particular interest in this chapter are more recent anatomic descriptions regarding (1) patchy rather than diffuse changes in UC, (2) upper gastrointestinal CD, and (3) epithelial neoplasia in IBD. The general aspects of the anatomic pathology of UC and CD are reviewed here, and the histopathologic assessment is covered in detail in Chapter 37. Classification of disease is always a challenge in medicine, and IBD are no different. For this chapter the strategy for classification separates inflammatory diseases with a known etiology from idiopathic IBD. It also nearly excludes diseases in which the bowel is secondarily involved by systemic diseases (such as Behcet syndrome). However, even within IBD one can subclassify the diseases based on fulminant course, extent of colitis, and indeterminate clinicopathologic disease. Thus, it is important to preserve some large diagnostic groups for the purpose of rapid understanding and communication, and for this reason we stress separating IBD into the two major groups: UC and CD. Smaller concerns addressing ulcerative proctitis or indeterminate colitis are less strongly treated. There are ample anatomic pathologic features to separate UC and CD, but also some unifying principles. Fortunately, a good foundation of pathologic principles helps to understand the medically relevant aspects of IBD. All of IBD has, at its pathophysiologic root, chronic inflammation with activity. Long-standing inflammation has the ability to injure the bystander organ, often beyond the ability for repair and normal function. Like any chronic inflammatory process, the longterm consequences are parenchymal damage, atrophy, fibrosis, and loss of function to the injured anatomic compartment. Like so many other chronic inflammatory processes in the gastrointestinal (GI) tract there is an increased risk of malignancy. Thus, the pathophysiologic sequelae of UC and CD are in parallel with other organs of the GI system which suffer chronic inflammatory injury; the examples

ObjectiveChronic diseases, such as inflammatory bowel disease (IBD), can impact negatively on education and social development. Examining the impact of IBD on school/college attendance for children and young people (CYP)...

Inflammatory bowel diseases (IBD) affect >3 million Americans and are associated with tremendous economic burden. Direct patient-level financial impacts, financial distress, and financial toxicity are less well understood. We aimed to summarize the literature on patient-level financial burden, distress, and toxicity associated with IBD in the United States. We conducted a literature search of US studies from 2002 to 2022 focused on direct/indirect costs, financial distress, and toxicity for patients with IBD. We abstracted study objectives, design, population characteristics, setting, and results. Of 2,586 abstracts screened, 18 articles were included. The studies comprised 638,664 patients with IBD from ages 9 to 93 years. Estimates for direct annual costs incurred by patients ranged from $7,824 to $41,829. Outpatient costs ranged from 19% to 45% of direct costs, inpatient costs ranged from 27% to 36%, and pharmacy costs ranged from 7% to 51% of costs. Crohn's disease was associated with higher costs than ulcerative colitis. Estimates for indirect costs varied widely; presenteeism accounted for most indirect costs. Severe and active disease was associated with greater direct and indirect costs. Financial distress was highly prevalent; associated factors included lower education level, lower household income, public insurance, comorbid illnesses, severity of IBD, and food insecurity. Higher degrees of financial distress were associated with greater delays in medical care, cost-related medication nonadherence, and lower health-related quality of life. Financial distress is prevalent among patients with IBD; financial toxicity is not well characterized. Definitions and measures varied widely. Better quantification of patient-level costs and associated impacts is needed to determine avenues for intervention.

Gastrointestinal ACE2, COVID-19 and IBD: Opportunity in the Face of Tragedy?

IntroductionA growing body of evidence supports use of therapeutic drug monitoring (TDM) in improving efficacy and cost-effectiveness of anti-TNF therapy in patients with inflammatory bowel disease (IBD), supported by AGA...

New models of care in IBD in changing times.

Purpose: Current understanding of Inflammatory Bowel Disease (IBD) and Irritable Bowel Syndrome (IBS) holds them as completely distinct entities, with IBD as an organic disease and IBS as a functional syndrome. Some studies hypothesize a relationship between the two disorders. A better understanding of the molecular pathways involved in the causation or response mechanisms of these two disorders would advance diagnostic testing and treatment of patients. We describe here the overlap of two sets of gene expression biomarkers that have significant diagnostic ability in IBD and IBS. Methods: We applied Exagen's proprietary in silico data analysis engine1 Coperna™ to publicly available full-genome expression microarray data from 85 IBD patients and 42 normal controls2. Results of those discovery phase IBD analyses were used to select a small set of 10 genes for diagnostic performance optimization in this independently ascertained pilot study of prospective cohorts of 91 patients with Ulcerative Colitis, 98 patients with Crohn's Disease, 98 patients with IBS, and 98 healthy individuals free from GI symptoms. Each IBD and IBS patient was diagnosed by a board-certified gastroenterologist. The IBD diagnoses were confirmed by endoscopy; the IBS diagnoses used Rome I criteria. The study was IRB approved and all subjects gave informed consent. Peripheral blood samples and clinical data were collected from all patients. Expression data were obtained from peripheral whole blood samples (with no mononuclear enrichment) by isolating total mRNAs, synthesizing cDNAs, and performing real-time quantitative PCR. Expression levels of the 10 candidate biomarker genes were assayed on each patient specimen and normalized to a within-patient reference gene. Results: Optimal scoring algorithms for classification of patients as IBD versus normal and IBS versus normal were derived separately using the expression levels of the 10 genes assayed in these pilot study patients. The optimal gene set for each test and each set's performance is indicated in Table 1. The classification results had odds ratios of 23.0 and 28.3, respectively, with both P-values < 2 × 10−16. Two genes were common to both diagnostic marker sets.Table 1: Highly significant expression biomarker sets in IBD and IBS*.Conclusion: The genes identified as diagnostic for the comparisons in this pilot study reveal an overlap between IBD and IBS patients. This overlap of highly statistically significant biomarkers suggests a shared biology. Additional studies are necessary to determine whether these genes have a causative role or are part of a common response mechanism.

Despite advances in our understanding of inflammatory bowel disease (IBD) pathogenesis and increased ability to treat patients with severe and refractory disease, patients continue to suffer from disease complications, and increasing numbers of both Crohn’s disease (CD) and ulcerative colitis (UC) patients are admitted annually in the USA. The rapid evolution in IBD medications and treatment paradigms has contributed to a disparity in clinical care which may vary between expert centers routinely treating large numbers of IBD patients and hospitals with low annual IBD admissions. High-volume centers handling in excess of 150 IBD annual admissions have improved operative and inpatient outcomes compared with hospitals caring for IBD patients less frequently. Although the precise reason for this disparity in clinical outcomes is not known, we hypothesize that expert centers provide superior IBD supportive therapy. This supportive care includes additional diagnostic and therapeutic approaches to help patients achieve optimal outcomes. We review information regarding disparities in the quality of IBD clinical care then focus on supportive therapy for IBD patients, including diagnostic approaches to identify confounding factors contributing to poor IBD outcome, supportive therapeutic approaches to optimize the outcome in hospitalized IBD patients, and future directions exploring brain-body interaction in the treatment of pain, stress and sleep deprivation in patients suffering from IBD.

INTRODUCTION: A growing body of evidence supports use of therapeutic drug monitoring (TDM) in improving efficacy and cost-effectiveness of anti-TNF therapy in patients with inflammatory bowel disease (IBD). Existing and evolving knowledge of TDM in clinical practice is less well understood. Our objective was to assess attitudes and barriers to TDM use with anti-TNF's in the UK. METHODS: A 17-question survey was distributed to members of the British Society of Gastroenterology. Information on clinician characteristics, demographics, use and barriers towards implementing TDM with anti-TNF's was collected. Logistic regression was used to predict factors influencing TDM use. RESULTS: 243 respondents participated (51.6% male) of which 237 respondents met inclusion criteria; treating &gt;5 IBD patients and at least 1 with an anti-TNF per month. Of the total respondents, 45% were Consultant Gastroenterologists (GI), 40% IBD Nurse Specialists (CNS) and 15% GI Specialist Registrars (SPR). Of these 237 respondents, TDM was used by 95.7% for secondary loss of response; 71.4% for primary non-response and 53.6% used TDM proactively. Barriers for TDM use were time lag in receiving results (27.1%), lack of awareness of guidelines (15.6%), and cost (11.9%). Clinicians working at a teaching hospital were more likely to use TDM compared to a district hospital (OR 2.6, 95% CI 0.71-9.8). IBD CNS and GI SPR used TDM more often, when compared to Consultant GI (OR 2.6, 95% CI 0.69-10 &amp; OR 1.5, 95% CI 0.3-7.2 respectively). Clinicians practising for &gt;20 years were more likely to check TDM than less experienced clinicians (OR 4.1, 95% CI 0.4-41.8). Clinicians with large volume IBD practice (&gt;50% IBD patients per month) were more likely to check TDM than those seeing fewer IBD patients (OR 45.6, 95% CI 7.5-275). Proactive TDM was more likely to be used by clinicians working in a tertiary care setting (OR 2.25, 95% CI 0.84-6.05), IBD CNS (OR 1.2, 95% CI 0.6-2.1), clinicians managing large volume IBD practice (OR 10.8, 95% CI 1.2-90) and clinicians with 5-9 years of experience in practice (OR 2.6 &amp; CI 1.04-6.42). CONCLUSION: Significant barriers to TDM implementation in the UK are time lag from test to result, lack of awareness of current guidelines and evolving knowledge, cost and less experience. Validation of point of care testing, lower cost assays, and wider dissemination of current evolving paradigms with updated recommendations may further optimise treatment with anti-TNF therapies.