Clinical Application of Intestinal Ultrasound in Inflammatory Bowel Disease.

PURPOSE OF REVIEW: Intestinal ultrasound (IUS) is a non-invasive, accurate, and well-tolerated tool that provides real-time assessment of inflammatory bowel disease (IBD) activity and is therefore an ideal monitoring tool. This review describes the evolving role of IUS in each phase of clinical management of IBD. RECENT FINDINGS: Accumulating evidence has demonstrated that IUS is an excellent tool for the assessment of suspected IBD, with a very high negative predictive value. It accurately assesses disease activity, disease complications, and in the pre-treatment phase, provides a benchmark for subsequent follow-up. IUS can detect early therapeutic response and correlates well with other established monitoring modalities with arguably superior predictive capabilities and ability to assess a deeper degree of remission, transmural healing (TH). IUS has a crucial role in the management of IBD and has ushered in a new era of monitoring with more rapid evaluation and the opportunity for early optimization, deeper therapeutic targets, and improved outcomes.

Real World Clinical Effectiveness and Safety of Ozanimod in the Treatment of Ulcerative Colitis: 1-Year Follow-Up from a Tertiary Center.

BACKGROUND: Ozanimod is a first-in-class Sphingosine-1-phosphate (S1P) receptor modulator approved for the treatment of moderately to severely active ulcerative colitis (UC). Real world data describing use of ozanimod are limited. AIM: To provide 1-year follow-up results of our UC patient cohort treated with ozanimod. METHODS: This prospective, observational cohort study includes consecutive patients who initiated ozanimod at the University of Chicago IBD Center between 5/2021 and 12/2022. We collected demographic, clinical, and laboratory data. Clinical disease activity was prospectively assessed using the Simple Clinical Colitis Activity Index. RESULTS: Forty-five patients with UC initiated ozanimod therapy and were included in the effectiveness analysis. The median age was 35 years (interquartile range (IQR) 28-52), median disease duration of 6 years (IQR 3-13), 26 (58%) were male, 23 (51%) had extensive colitis, 34 (76%) had previous advanced therapy exposure. Thirty-four patients had clinically active UC at the time of ozanimod initiation; week 10 clinical response and remission rates were 58% and 53%, respectively. By week 52, the rates were 25% for both clinical response and remission. In the 12 (39%) patients with a > 75% reduction in absolute lymphocyte count, numerically greater induction clinical response and remission rates were observed (80% vs 54%, p = 0.4 and 75% vs 53%, p = 0.4, respectively). There were no episodes of symptomatic bradycardia and no other new safety signals. CONCLUSION: Ozanimod effectively induced clinical response and remission patients with largely treatment refractory UC, however, had modest long-term effectiveness. The safety profile was favorable with no new signals.

What Does Disease Progression Look Like in Ulcerative Colitis, and How Might It Be Prevented?

Ulcerative colitis (UC) has been characterized by inflammation limited to the mucosa. Although sustained and durable remission has been associated with mucosal healing, the recurrent phenomenon of persistent clinical disease activity despite mucosal healing has been observed in clinical practice and across pivotal trials. Over time, UC appears to confer an increased risk of progression, defined as changes of disease phenotype; adverse transmural effects on the bowel wall; increased risk of neoplasia development; worsening colorectal function; and increased risk of colectomy, hospitalizations, and other extraintestinal comorbidities. Although the treatment paradigm for Crohn's disease has shifted toward early aggressive intervention to prevent disease progression and irreversible bowel damage, such urgency in efforts to halt disease progression in UC have been largely overlooked. This review summarizes the multiple facets of UC contributing to a modified perception of the disease as a progressive one. We propose further study of the natural history and priorities for further treatment goals that include these considerations.

Upadacitinib Is Effective and Safe in Both Ulcerative Colitis and Crohn's Disease: Prospective Real-World Experience.

BACKGROUND & AIMS: Upadacitinib is a novel selective Janus kinase 1 inhibitor that has shown efficacy in the treatment of moderate to severe ulcerative colitis (UC) and Crohn's disease (CD), and has received Food and Drug Administration approval for UC. We report a large real-world experience with upadacitinib in UC and CD. METHODS: We performed a prospective analysis of clinical outcomes on upadacitinib in patients with UC and CD using predetermined intervals at weeks 0, 2, 4, and 8 as part of a formalized treatment protocol at our institution. We used the Simple Clinical Colitis Activity Index and the Harvey-Bradshaw index, as well as C-reactive protein and fecal calprotectin to assess efficacy, and also recorded treatment-related adverse events and serious adverse events. RESULTS: A total of 105 patients were followed up for 8 weeks on upadacitinib, 84 of whom (44 UC patients, 40 CD patients) were initiated because of active luminal or perianal disease and included in the analysis. One hundred percent previously received anti-tumor necrosis factor therapy, and 89.3% had received 2 or more advanced therapies. At 4 and 8 weeks of treatment for UC, 19 of 25 (76.0%) and 23 of 27 (85.2%) achieved clinical response and 18 of 26 (69.2%) and 22 of 27 (81.5%) achieved clinical remission, respectively. Of those who previously were tofacitinib-exposed, 7 of 9 (77.8%) achieved clinical remission by 8 weeks. In CD, 13 of 17 (76.5.%) achieved clinical response and 12 of 17 (70.6%) achieved clinical remission by 8 weeks. Of those with increased fecal calprotectin and C-reactive protein levels, 62% and 64% normalized by week 8, respectively. Results were seen as early as week 2 in both UC and CD, with clinical remission rates of 36% and 56.3.%, respectively. Acne was the most commonly reported adverse event, occurring in 24 of 105 patients (22.9%). CONCLUSIONS: In this large real-world experience in medically resistant patients with UC or CD, we report that upadacitinib is rapidly effective and safe, including in those who had prior tofacitinib exposure. This study was approved by the Institutional Review Board at the University of Chicago (IRB20-1979).

P042 Early Versus Later Use of Vedolizumab In IBD: Patient Characteristics And Treatment Patterns In The Real World (RALEE).

BACKGROUND: Pivotal trials in inflammatory bowel disease (IBD) demonstrate that earlier use of biologics is associated with greater likelihood of response/remission, but multiple studies have identified that in the real world, biologic treatment is often delayed, thereby limiting optimal effectiveness and increasing likelihood of adverse outcomes. Further assessment of patient, provider, and payor factors that contribute to therapy choice is needed. We assessed utilization of vedolizumab (VDZ) and performed a real-world assessment using administrative datasets. Here, we describe the different treatment patterns and demographics of patients who received VDZ. METHODS: We identified VDZ-treated patients (aged ≥18 years) with Crohn's disease (CD) or ulcerative colitis (UC) in the MarketScan commercial and Medicare claims databases from 2017 to 2019 and included those who had continuous enrollment in the same health plan for ≥12 months prior to their initial IBD diagnostic claim, ≥1 VDZ claim after the initial IBD diagnosis, and continuous enrollment for ≥12 months prior to and after their initial UC or CD diagnosis. Patients exposed to VDZ, anti-TNF, or other biologic therapy in the 12-month pre-index period were excluded. We pre-defined 5 treatment pathways: (1) EARLY VDZ - VDZ within 30 days of first IBD diagnostic claim; (2) DELAYED VDZ 1 - immunomodulators and then switch to VDZ; (3) DELAYED VDZ 2 - corticosteroids with immunomodulators prior to VDZ; (4) DELAYED VDZ 3 - 5-ASA with corticosteroids prior to VDZ; or (5) DELAYED VDZ 4 - 5-ASA with corticosteroids and immunomodulators prior to VDZ. Differences in patient baseline characteristics among these treatment pathways were analyzed descriptively. RESULTS: We identified 136,315 patients with UC and 103,591 with CD, from which 1,342 patients with UC (median age 43 years; 51.0% male; 96.4% commercially insured; 86.4% diagnosed in 2017) and 964 with CD (median age 45 years; 43.6% male; 94.6% commercially insured; 88.6% diagnosed in 2017) received VDZ and met criteria. The proportions of patients by treatment pathway were (UC|CD): EARLY VDZ (6.6%|9.6%); DELAYED VDZ 1 (7.5%|19.0%); DELAYED VDZ 2 (14.8%|36.8%); DELAYED VDZ 3 (37.6%|19.0%); DELAYED VDZ 4 (33.4%|15.6%). Among patients with UC, EARLY VDZ vs DELAYED VDZ cohorts had median age of 40 vs 44 years and proportion of men of 46.1% vs 51.4%. Among patients with CD, EARLY VDZ vs DELAYED VDZ had median age of 43 vs 45 years and proportion of men of 39.8%% vs 43.9%. For both indications, no meaningful differences among treatment groups by geographic region, payor type (i.e., commercial vs Medicare), and year of diagnosis were observed. CONCLUSION: In this administrative real-world dataset, fewer than 10% of patients with IBD were treated with VDZ within 30 days of diagnosis, and these patients were more likely to be younger and women. These findings are distinct from guidelines suggesting VDZ may be used earlier, or due to its safety profile, preferentially in older patients at higher risk for infection. Further analyses of safety and effectiveness outcomes are underway.

Efficacy and Follow-up of Segmental or Subtotal Colectomy in Patients With Colitis-Associated Neoplasia.

The historical approach to neoplasia in the setting of chronic colitis was to perform a total proctocolectomy. Recent consensus and society guidelines1-3 suggest that when dysplastic lesions can be removed endoscopically, continued surveillance is appropriate. This is based on improvements in optical technologies and the low risk of metachronous colorectal carcinoma in these patients.4-6 We hypothesized that if a lesion was completely removed surgically and followed up endoscopically, metachronous colorectal carcinoma would be a rare occurrence. Thus, segmental resection may be offered as a definitive surgery in patients with chronic colitis and localized colorectal neoplasia in whom endoscopic resection is not feasible. Retention of the distal colon/rectum is expected to result in an overall improved quality of life compared with permanent ileostomy or an ileoanal J-pouch. Here, we report our experience and follow-up evaluation of segmental resections for preoperative neoplasia in patients with Crohn's disease (CD) or ulcerative colitis (UC).

Ustekinumab Is Effective for the Treatment of Chronic Antibiotic-Refractory Pouchitis.

BACKGROUND: Chronic antibiotic-refractory pouchitis (CARP) occurs in up to 15% of patients with ulcerative colitis (UC) following proctocolectomy with ileal pouch-anal anastomosis (IPAA). AIM: To investigate the effectiveness of ustekinumab in the treatment of CARP. METHODS: This was a retrospective single-center study of UC patients with an IPAA, who subsequently developed CARP and received ustekinumab with standard Crohn's disease (CD) dosing between 2016 and 2018. Patients with CD of the pouch were excluded. Demographic, clinical, and endoscopic data were collected. Outcomes included a change in the endoscopic subscore of the Pouchitis Disease Activity Index (PDAI), change in the ulcerated surface area, clinical response, and the number of bowel movements per 24 h. RESULTS: Twenty-four patients with CARP were included for analysis. Median follow-up time was 12.9 months (IQR 7.9-16). Twelve patients (50%) had a clinical response with the median number of bowel movements within 24 h decreasing from 8 (IQR, 5-12) to 6 (IQR, 5-8) P = 0.002. Thirteen patients had pouchoscopies available post-ustekinumab treatment. In these patients, the median endoscopic subscore of the PDAI decreased from 5 (IQR, 3-6) to 4 (IQR, 2-5), P = 0.016. Likewise, among these thirteen patients, nine (69%) had an ulcerated surface area > 10% before ustekinumab treatment; after treatment with ustekinumab, only four patients (31%) still had an ulcerated surface area of > 10%. CONCLUSIONS: This is the largest study of ustekinumab treatment for patients with chronic antibiotic-refractory pouchitis. We found that ustekinumab therapy led to the improvement in clinical and endoscopic endpoints.

Patients With Ulcerative Colitis and Primary Sclerosing Cholangitis Frequently Have Subclinical Inflammation in the Proximal Colon.

BACKGROUND & AIMS: Patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) have a high risk of colonic neoplasia. Neoplasia frequently develops in the proximal colon in patients with PSC. Histologic inflammation is an independent risk factor for the development of neoplasia; we investigated whether patients with UC and PSC have more subclinical disease activity than patients with UC alone. METHODS: We performed a retrospective analysis of data from 143 patients (205 examinations) with ulcerative pancolitis who were in clinical remission and treated at a tertiary medical center from May 2011 through May 2016. Endoscopic and histologic activity were compared between patients with PSC (from 36 examinations) and without PSC (from 169 examinations). Disease activity was scored per colonic segment using a modified Mayo endoscopic subscore and histologic assessment. In each colonic segment, differences in disease activity and the degree of discordance between endoscopic and histologic inflammation among UC patients with and without PSC were compared. RESULTS: Patients with UC-PSC had significantly more subclinical endoscopic (odds ratio [OR], 4.21; 95% CI, 1.67-10.63) and histologic activity (OR, 5.13; 95% CI, 2.25-11.68) in the right colon, as well as greater degree of histologic than endoscopic inflammation in the proximal colon (OR, 3.14, 95% CI, 1.24-7.97), compared with patients without PSC. Patients with UC-PSC had significantly less histologic activity in the rectum on multivariate analysis (OR, 0.24; 95% CI, 0.08-0.72). CONCLUSIONS: Patients with UC and PSC who are in clinical remission are significantly more likely to have endoscopic and histologic inflammation in the right colon than patients with UC without PSC. Our findings provide insight into cause of colorectal cancer in UC patients with PSC.

Assessment of peri-polyp biopsy specimens of flat mucosa in patients with inflammatory bowel disease.

BACKGROUND AND AIMS: When colon polyps are removed in the setting of inflammatory bowel disease (IBD) involving the large intestine, biopsy sampling of the flat mucosa surrounding such polyps have been recommended, but there are no data to support this practice. METHODS: We reviewed endoscopic and pathologic findings in IBD patients who had dysplastic polyps removed and biopsy sampling of the adjacent flat mucosa. We assessed risk for subsequent neoplasia based on the presence or absence of dysplasia in the peri-polyp flat mucosa and based on number and grade of index polypoid lesions. Kaplan-Meier survival analysis was performed. RESULTS: Fifty-six IBD patients (68% ulcerative colitis [UC]) underwent 102 colonoscopies, in which 129 dysplastic polyps were resected. Five hundred three biopsy procedures of the surrounding flat mucosa were performed (mean, 3.9 biopsy samples per polyp), of which 16 (3.2%) were dysplastic. Thirty-four patients (21 UC) had follow-up in a median of 1.7 years (range, .02-15) and 147 colonoscopies. The presence of dysplasia in peri-polyp biopsy specimens during index colonoscopy was not associated with risk of developing high-grade dysplasia (HGD) or cancer (Pearson χ2 test = .19). The size and number of dysplastic polyps were not predictive of neoplastic outcomes, but the probability of developing subsequent advanced neoplasia for polypoid low-grade dysplasia was 18%, 29%, and 40% by 1, 3, and 5 years, respectively, and for polypoid HGD was 50%, 60%, and 70% by 1, 3, and 5 years, respectively (hazard ratio, 7.0; standard error, 4.8). CONCLUSIONS: In patients with IBD-associated colitis, biopsy sampling of the mucosa adjacent to discrete dysplastic polypoid lesions are low yield and do not predict findings in follow-up examinations. However, the grade of dysplasia of the polyp itself is predictive of subsequent advanced neoplasia.

Using a Treat-to-Target Management Strategy to Improve the Doctor-Patient Relationship in Inflammatory Bowel Disease.

The doctor-patient relationship (DPR) in inflammatory bowel disease (IBD) has been facing new challenges, in part due to the substantial progress in medical and surgical management and also due to the rapid expansion of patient access to medical information. Not surprisingly, the complexity of IBD care and heterogeneity of the disease types may lead to conflict between a physician's therapeutic recommendations and the patient's wishes. In this commentary, we propose that the so-called "treat-to-target" approach of objective targets of disease control and serial adjustments to therapies can also strengthen the DPR in IBD by enabling defined trials of alternative approaches, followed by a more objective assessment and reconsideration of treatments. We contend that such respect for patient autonomy and the use of objective markers of disease activity improves the DPR by fostering trust and both engaging and empowering patients and physicians with the information necessary to make shared decisions about therapies.

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.

Real-World Persistence of Successive Biologics in Patients With Inflammatory Bowel Disease: Findings From ROTARY.

BACKGROUND: Patients with inflammatory bowel disease (IBD) may receive multiple successive biologic treatments in clinical practice; however, data are limited on the comparative effectiveness of biologics and the impact of treatment sequence on outcomes. METHODS: The ROTARY (Real wOrld ouTcomes Across tReatment sequences in inflammatorY bowel disease patients) study was a retrospective, observational cohort study conducted using data from the Optum Clinical Database between January 1, 2012, and February 29, 2020. Adult patients with Crohn's disease (CD) or ulcerative colitis (UC) who received 2 biologics successively were included. Biologic treatment sequences were analyzed descriptively. Cox proportional hazards models, adjusted for baseline demographics and clinical characteristics, were used to estimate the hazard ratio of switching or discontinuation for each first- and second-line biologic compared with first- and second-line adalimumab, respectively. RESULTS: In total, 4648 patients with IBD (CD, n = 3008; UC, n = 1640) were identified. Most patients received tumor necrosis factor α antagonist (anti-TNFα) treatment followed by another anti-TNFα treatment or vedolizumab. Vedolizumab and infliximab had 39.4% and 34.6% lower rates of switching or discontinuation than adalimumab, respectively, as first-line biologics in patients with CD and 30.8% and 34.3% lower rates as first-line biologics in patients with UC, respectively. Vedolizumab, infliximab, and ustekinumab had 47.2%, 40.0%, and 43.5% lower rates of switching or discontinuation than adalimumab, respectively, as second-line biologics in CD and 56.5%, 43.0%, and 45.6% lower rates as second-line biologics in patients with UC, respectively. CONCLUSIONS: Although anti-TNFα treatments were most commonly prescribed, the adjusted rates of discontinuation for adalimumab as both a first- and second-line biologic were higher than for vedolizumab, infliximab, or ustekinumab.

Patients with inflammatory bowel disease are commonly treated with different sequences of biologics. This study shows that patients who receive adalimumab as their first or second biologic treatment either stop or switch to another biologic at a greater rate than those who are treated with vedolizumab, infliximab, and ustekinumab.

Inflammation in the proximal colon is a risk factor for the development of colorectal neoplasia in inflammatory bowel disease patients with primary sclerosing cholangitis.

Background: Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) have an increased risk of developing colorectal neoplasia (CRN) in the proximal colon. Objectives: To evaluate whether duration and severity of inflammation are linked to the development of CRN in this population. Design: Retrospective, case-control chart review of patients with PSC and IBD at a tertiary care center. Methods: Disease activity was scored per colonic segment at each colonoscopy prior to the first instance of observed CRN using a modified Mayo endoscopic sub-score and histologic assessment. Patients in the CRN-positive group were compared to controls that did not. Results: In all, 72 PSC-IBD patients with no history of CRN were identified, 13 of whom developed CRN after at least one colonoscopy at our institution. Patients in the CRN-positive group had significantly more endoscopic (p < 0.01) and histologic (p < 0.01) inflammation in the right compared to the control group prior to the development of dysplasia. There was significantly greater endoscopic inflammation in the segment of the colon with a dysplastic lesion than other segments of the colon (p = 0.018). Patients with moderate/severe lifetime endoscopic (p = 0.02) or histologic inflammation (p = 0.04) score had a lower probability of remaining free of dysplasia during follow-up. Nearly half of the patients with dysplasia had invisible lesions found on random biopsy. Conclusions: Endoscopic and histologic inflammation in the proximal colon are risk factors for CRN in patients with PSC-IBD. PSC-IBD patients frequently have subclinical inflammation, and these findings support the practice of regular assessment of disease activity and random biopsy of inflamed and uninflamed areas in patients with PSC with the goal of reducing inflammation to prevent the development of CRN.

Patients with PSC and IBD have not been examined as a cohort to assess for risk factors for CRN. We found that severe inflammation in the proximal colon is the main risk factor for CRN in these patients.

Achieving Histologic Normalization in Ulcerative Colitis Is Associated With a Reduced Risk of Subsequent Dysplasia.

BACKGROUND: Complete histologic normalization is associated with improved clinical outcomes in ulcerative colitis (UC). However, it is currently unknown what effect achieving histologic normalization has on the development of dysplasia. METHODS: We performed a retrospective analysis of 495 patients with a confirmed diagnosis of UC from a tertiary center. Patients were categorized according to the best histologic assessment they had during their disease course: histologic normalization, histologic quiescence, or persistent histologic activity. We assessed dysplasia rates in these patient groups after achieving histologic normalization or histologic quiescence, or 8 years after UC diagnosis in those with persistent histologic activity. Kaplan-Meier graphs and Cox regression analyses were performed to estimate this effect. RESULTS: The incidence rate of dysplasia development after achieving histologic normalization was statistically significantly less when compared with the incidence rate after achieving histologic quiescence (P = 0.001) and in those with persistent histologic activity 8 years after UC diagnosis (P = 0.033). In multivariate analysis, at any point throughout UC duration, dysplasia development was statistically lower in those with histologic normalization (adjusted hazard ratio [aHR], 0.32; 95% confidence interval [CI], 0.13-0.81) but not in those with histologic quiescence (aHR, 0.52; 95% CI, 0.25-1.10), compared with those with persistent histologic inflammation. When assessing the time after achieving histologic normalization, histologic quiescence, or 8 years post UC diagnosis in those with persistent histologic activity, we found that patients with histologic normalization had a subsequent decreased risk of developing dysplasia (aHR, 0.09; 95% CI, 0.01-0.72), compared with patients without normalization. CONCLUSIONS: Histologic normalization is associated with a decreased risk in patients with UC of developing subsequent dysplasia, compared with patients without histologic normalization. These findings have implications for surveillance intervals.