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Background & Aims Mucosal healing, determined by histologic analysis, is a potential therapeutic target for patients with ulcerative colitis (UC). However, the histologic features of tissue normalization, as an outcome of treatment, have not been well described. We examined the prevalence and predictive values of normalization of the colonic mucosa, based on histologic analysis (histologic normalization) in patients with UC, and determined its association with risk of clinical relapse, compared with histologic disease quiescence and endoscopic mucosal healing. Methods We performed a retrospective study of 646 patients with confirmed UC who underwent colonoscopy at a tertiary medical center from August 2005 through October 2013. We reviewed reports from pathology analyses of random mucosal biopsies from each colon segment, and categorized them into 3 groups based on histology findings: (1) normalization (completely normal mucosa with no features of chronicity present), (2) quiescence (crypt atrophy or branching without signs of active inflammation including erosions, abscesses, or focal neutrophil infiltration), or (3) active disease (epithelial infiltration by neutrophils, crypt abscesses, erosions, or ulceration). Histology findings were compared with clinical and endoscopic findings. We assessed variables associated with histology findings and, in patients in clinical remission (Simple Clinical Colitis Activity Index score ≤2 and subscore of ≤1 for stool frequency or rectal bleeding), predictive values for clinical relapse at follow-up evaluations 6 months later or more were calculated. Results Of the 646 patients included in the study, 60% had endoscopic mucosal healing, 40% had histologic quiescence, and 10% had histologic normalization. The level of agreement between mucosal and histologic activity was moderate (agreement for 68% of samples; k = 0.50; P < .001). On multivariate analysis, only proctitis associated with histologic normalization (P = .002). Of 310 patients in clinical remission at initial review, 25% had a clinical relapse, after a median time of 16 months (interquartile range, 10–23 months). Histologic normalization was independently associated with increased odds of relapse-free survival compared with histologic quiescence (hazard ratio, 4.31; 95% confidence interval, 1.48–12.46; P = .007) and histologic activity (hazard ratio, 6.69; 95% confidence interval, 2.16–20.62; P = .001); mucosal healing was not associated with increased odds of relapse-free survival compared with no mucosal healing (hazard ratio, 1.02; 95% confidence interval, 0.56–1.85; P = .954). Conclusions Histologic normalization of colonic mucosa can be used as a clinical endpoint for patients with UC. We associated histologic normalization with increased odds of relapse-free survival compared to endoscopic healing or histologic quiescence. Further studies are needed to determine whether histologic normalization should be a goal of treatment for patients with UC.

Summary Background The current COVID‐19 pandemic, caused by SARS‐CoV‐2, has emerged as a public health emergency. All nations are seriously challenged as the virus spreads rapidly across the globe with no regard for borders. The primary management of IBD involves treating uncontrolled inflammation with most patients requiring immune‐based therapies. However, these therapies may weaken the immune system and potentially place IBD patients at increased risk of infections and infectious complications including those from COVID‐19. Aim To summarise the scale of the COVID‐19 pandemic, review unique concerns regarding IBD management and infection risk during the pandemic and assess COVID‐19 management options and drug interactions in the IBD population. Methods A literature review on IBD, SARS‐CoV‐2 and COVID‐19 was undertaken and relevant literature was summarised and critically examined. Results IBD patients do not appear to be more susceptible to SARS‐CoV‐2 infection and there is no evidence of an association between IBD therapies and increased risk of COVID‐19. IBD medication adherence should be encouraged to prevent disease flare but where possible high‐dose systemic corticosteroids should be avoided. Patients should exercise social distancing, optimise co‐morbidities and be up to date with influenza and pneumococcal vaccines. If a patient develops COVID‐19, immune suppressing medications should be withheld until infection resolution and if trial medications for COVID‐19 are being considered, potential drug interactions should be checked. Conclusions IBD patient management presents a challenge in the current COVID‐19 pandemic. The primary focus should remain on keeping bowel inflammation controlled and encouraging medication adherence.

Background and aims Intestinal ultrasound (IUS) is an accurate, patient-centered 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 3 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: Eleven experts representing 7 countries identified four key parameters including (1) bowel wall thickness (BWT) (2) bowel wall stratification (3) hyperemia of the wall [color Doppler imaging] and (4) inflammatory mesenteric fat. Blind Read: Each variable exhibited moderate to substantial reliability. Optimal, standardized image and cineloop acquisition were established. Second Blind Read and score development: intra-class correlation coefficient (ICC) for BWT was almost perfect 0.96 (0.94-0.98). All 4 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&lt;0.001)]. Conclusions Using expert consensus and standardized approaches, identification of key activity measurements on IUS has been achieved and a segmental activity score has been proposed, demonstrating excellent reliability.

Background: The impact of pregnancy on levels of biologic agents in patients with IBD is undefined and time to elimination in vedolizumab-exposed infants is unknown. Aims: To determine the effect of pregnancy on infliximab, adalimumab and vedolizumab levels and to study infant vedolizumab clearance Methods: In a prospective observational study, maternal drug levels were measured pre-conception, in each trimester, at delivery and postpartum. The association between drug levels and gestation in weeks was assessed using generalised estimating equation modelling. Infant vedolizumab levels were performed at birth (cord blood), 6 weeks and 3 months or until undetectable. Results: We included 50 IBD patients (23 on infliximab, 15 on adalimumab and 12 on vedolizumab) with at least two intrapartum observations, plus 5 patients on vedolizumab with only mother and baby samples at delivery. Modelling showed no change in adalimumab levels, an increase in infliximab levels of 0.16 (95% CI 0.08-0.24) µg/L/week (P < 0.001) and a decrease of 0.18 (95% CI: −0.33 to −0.02) µg/L/week (P = 0.03) for vedolizumab. In 17 mother-baby pairs, median infant vedolizumab levels at birth were lower than maternal levels (P < 0.05) with an infant:maternal ratio of 0.7 (IQR 0.5-0.9). Vedolizumab was undetectable between 15 and 16 weeks of age in all 12 infants completing follow-up testing. Conclusions: During pregnancy, adalimumab levels remain stable, while infliximab levels increase and vedolizumab levels decrease. However, the increments were small suggesting that intrapartum therapeutic drug monitoring and dose adjustment are not indicated. Unlike infliximab and adalimumab, infant vedolizumab levels are lower in cord blood than in mothers and appear to clear rapidly.

Summary Background Blocking of lymphocyte trafficking to bile ducts is a potential mechanism to alter the disease course of patients with primary sclerosing cholangitis (PSC). Aim To describe the effect of the α4β7 integrin antibody, vedolizumab, on liver biochemistry and disease activity in patients with PSC and inflammatory bowel disease (IBD). Methods This is a retrospective multi-center study of adult patients with a diagnosis of both IBD and PSC. The primary outcome was change in serum alkaline phosphatase level at weeks 14 and 30. Secondary outcomes included changes in other liver biochemistries and in clinical outcomes for the bowel disease. A safety analysis for adverse events was performed. Results 34 patients (16 Crohn’s disease, 18 ulcerative colitis) were included. Nine (26%) had a history of liver transplant. Median follow-up on vedolizumab was 9 months [IQR: 7–16]. There was no overall change in serum alkaline phosphatase level with vedolizumab therapy (median 268 [IQR:105–551] IU/L at baseline versus 249 [IQR:183–634] IU/L, P=0.99 at week 30). No significant changes in other liver biochemistries or the Mayo PSC Risk Score were demonstrated at week 30. Clinical remission was achieved at week 30 in 55% of Crohn’s disease and 29% of ulcerative colitis patients. Seven (21%) patients ceased vedolizumab; six patients stopped therapy due to persistent IBD activity and one for worsening of liver biochemistries. Conclusion Vedolizumab treatment in patients with PSC and IBD did not improve liver biochemistry but was associated with improvement in bowel disease and a favorable safety profile.

BACKGROUND & AIMS: Deep remission, based on clinical remission and evidence of healing during endoscopic evaluation, are goals of medical treatments for Crohn's disease (CD). We investigated whether histologic healing is associated with outcomes of patients with CD ileitis. METHODS: We performed a retrospective study of 101 patients with CD (52% male) isolated to the terminal ileum who had a colonoscopy between September 2005 and June 2015. Our analysis included patients in clinical remission at colonoscopy who had biopsies collected from colon and ileum. The ileum was evaluated for endoscopic healing (no ulceration) and histologic evidence of healing (no active inflammation, erosions, ulceration, or neutrophil infiltration). We compared times of clinical relapse-free survival, medication escalation, corticosteroid use, or hospitalization secondary to disease activity between patients with and without histological and endoscopic healing, followed for a median 21 months. We identified factors associated with survival using Kaplan Meier analysis and Cox proportional hazard model. RESULTS: At ileo-colonoscopy, 63% of patients had endoscopic healing and 55% had histologic evidence of healing. The level of agreement between endoscopic and histologic activity was fair (62%, K [ 0.2250, P [ .0064). Forty-two patients had clinical relapse, 45 had medication escalation, 30 required corticosteroids, and 17 were hospitalized (3 required surgery). On multivariate analysis, only histologic healing was associated with decreased risk of clinical relapse (hazard ratio [HR], 2.05; 95% CI, 1.07-3.94; P [ .031), medication escalation (HR, 2.17; 95% CI, 1.2-3.96; P [ .011), and corticosteroid use (HR, 2.44; 95% CI, 1.17-5.09; P [ .018). No factors were associated with hospitalization. CONCLUSIONS: In patients with ileal CD in clinical remission, histologic healing but not endoscopic healing is associated with decreased risk of clinical relapse, medication escalation, or corticosteroid use.

Combination therapy of vedolizumab with either cyclosporin or tacrolimus is effective and safe at inducing and maintaining clinical remission in patients with CD and UC with up to 52 weeks of follow-up evaluation. Larger studies of the ability of calcineurin inhibitors to induce remission in patients on vedolizumab are warranted.