EFFICACY AND SAFETY OF USTEKINUMAB FOR CHRONIC POUCHITIS: A PROSPECTIVE OPEN-LABEL MULTICENTER STUDY.

BACKGROUND AND AIMS: Seventeen percent of patients with ulcerative colitis that undergo proctocolectomy with pouch surgery will develop chronic pouchitis. We evaluated the efficacy of ustekinumab for these patients. METHODS: We performed a prospective study of chronic pouchitis patients receiving ustekinumab intravenously at baseline (∼6mg/kg) and 90mg ustekinumab subcutaneously every 8 weeks thereafter. The modified pouchitis disease activity index (mPDAI) was assessed at baseline, week 16 and 48. The primary endpoint was the proportion of patients achieving steroid-free remission (mPDAI <5 and reduction by ≥2 points) at week 16. Secondary endpoints included the proportion of patients achieving remission at week 48, the proportion of patients achieving response (reduction of mPDAI by ≥2 points) at week 16 and 48, and change in mPDAI. RESULTS: We enrolled 22 patients (59% male, median age 42.2 years). Remission was achieved in 27.3% at week 16 and 36.4% at week 48. Response was achieved in 54.5% both at week 16 and 48. The median (IQR) mPDAI decreased from 8 (7-10) to 7 (4-9) at week 16 (p=0.007) and 4 (1.75-7.25) at week 48 (p<0.001). The clinical mPDAI subscore decreased from 3.5 (2-4) to 2 (1-3) at week 16 (p=0.009) and 1 (0-2.25) at week 48 (p=0.001). The endoscopic mPDAI subscore decreased from 5.5 (4-6) to 4 (3-6) at week 16 (p=0.032) and 3 (1.75-4.25) at week 48 (p=0.001). CONCLUSION: Ustekinumab was efficacious in half of the patients suffering from chronic pouchitis. Ustekinumab should therefore be positioned in the treatment algorithm of chronic pouchitis. (ClinicalTrials.gov Number NCT04089345).

Fibrostricturing Crohn's disease is marked by an increase in active eosinophils in the deeper layers.

INTRODUCTION: Approximately 50% of Crohn's disease (CD) patients develop intestinal strictures necessitating surgery. The immune cell distribution in these strictures remains uncharacterized. We aimed to identify the immune cells in intestinal strictures of CD patients. METHODS: During ileocolonic resections, transmural sections of terminal ileum were sampled from 25 CD patients and 10 non-inflammatory bowel disease (IBD) controls. Macroscopically, unaffected, fibrostenotic and inflamed ileum was collected and analysed for immune cell distribution (flow cytometry) and protein expression. Collagen deposition was assessed via a Masson's Trichrome staining. Eosinophil and fibroblast co-localization was assessed through immunohistochemistry. RESULTS: The Masson's Trichrome staining confirmed augmented collagen deposition in both the fibrotic as the inflamed region, though with a significant increased collagen deposition in fibrotic compared to inflamed tissue. Distinct Th1, Th2, regulatory T cells, dendritic cells and monocytes were identified in fibrotic and inflamed CD ileum compared to unaffected ileum of CD patients as non-IBD controls. Only minor differences were observed between fibrotic and inflamed tissue, with more active eosinophils in fibrotic deeper layers and increased Eosinophil Cationic Protein (ECP) protein expression in inflamed deeper layers. Lastly, no differences in eosinophil and fibroblast co-localization was observed between the different regions. CONCLUSION: This study characterized immune cell distribution and protein expression in fibrotic and inflamed ileal tissue of CD patients. Immunologic, proteomic and histological data suggest inflammation and fibrosis are intertwined, with large overlap between both tissue types. However strikingly, we did identify an increased presence of active eosinophils only in the fibrotic deeper layers, suggesting their potential role in fibrosis development.

Chronic kidney disease in inflammatory bowel disease, a systematic review and meta-analysis.

Inflammatory bowel disease (IBD) is associated with various immune mediated disorders including spondylarthritis, pyoderma gangrenosum, primary sclerosing cholangitis and uveitis. Chronic kidney disease (CKD) is defined by a reduction in kidney function (eGFR less than 60ml/min/1.73m2) and/ or damage markers that are present for at least three months, regardless of the aetiology. Case reports and cohort studies suggest that IBD is associated with CKD. The extent and magnitude of a potential association is unknown. A comprehensive search was conducted in EMBASE, MEDLINE, Web of Science, the Cochrane database, and SCOPUS. Two separate reviewers were involved in the process of article selection and evaluation. Odds ratios were calculated in those papers with a comparison between an IBD population and a non-IBD control population, the Mantel Haenszel test was employed, utilizing a random effect model. The systematic review was registered in PROSPERO (RD42023381927). Fifty-four articles were included in the systematic review. Of these, eight articles included data on prevalence of CKD in IBD patients (n = 102,230) vs. healthy populations (n = 762,430). Of these, diagnosis of CKD was based on ICD codes in five studies vs. on eGFR in three studies. The overall odds ratio of developing CKD in the IBD population is 1.59 (95%CI 1.31-1.93), without any difference between studies using diagnostic coding (OR 1.70 95%CI 1.33-2.19) vs. diagnosis based on eGFR (OR 1.36 95%CI 1.33-1.64). IBD is associated with a clinically meaningful increased CKD prevalence. We provide recommendations on diagnostic evaluation, as well as suggestions for future research.

Gut-associated lymphoid tissue attrition associates with response to anti-α4ß7 therapy in ulcerative colitis.

Vedolizumab (VDZ) is a first-line treatment in ulcerative colitis (UC) that targets the α4ß7- mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) axis. To determine the mechanisms of action of VDZ, we examined five distinct cohorts of patients with UC. A decrease in naïve B and T cells in the intestines and gut-homing (ß7+) plasmablasts in circulation of VDZ-treated patients suggested that VDZ targets gut-associated lymphoid tissue (GALT). Anti-α4ß7 blockade in wild-type and photoconvertible (KikGR) mice confirmed a loss of GALT size and cellularity because of impaired cellular entry. In VDZ-treated patients with UC, treatment responders demonstrated reduced intestinal lymphoid aggregate size and follicle organization and a reduction of ß7+IgG+ plasmablasts in circulation, as well as IgG+ plasma cells and FcγR-dependent signaling in the intestine. GALT targeting represents a previously unappreciated mechanism of action of α4ß7-targeted therapies, with major implications for this therapeutic paradigm in UC.

Accuracy of Information given by ChatGPT for patients with Inflammatory Bowel Disease in relation to ECCO Guidelines.

INTRODUCTION: As acceptance of AI platforms increases, more patients will consider these tools as sources of information. The ChatGPT architecture utilizes a neural network to process natural language, thus generating responses based on the context of input text. The accuracy and completeness of ChatGPT3.5 in the context of Inflammatory Bowel Disease remains unclear. METHODS: In this prospective study, 38 questions worded by IBD patients were inputted into ChatGPT3.5. The following topics were covered: 1) CD, UC and malignancy, 2) maternal medicine 3) infection and vaccination 4) complementary medicine. Responses given by Chat GPT were assessed for accuracy (1 - completely incorrect to 5 - completely correct) and completeness (3-point Likert scale; range 1 - incomplete to 3 - complete) by 14 expert gastroenterologists, in comparison with relevant ECCO guidelines. RESULTS: In terms of accuracy, most replies (84.2%) had a median score of ≥4 (IQR:2) and a mean score of 3.87 (SD: +/- 0.6). For completeness, 34.2% of the replies had a median score of 3 and 55.3 % had a median score of between 2 and <3. Overall, the mean rating was 2.24 (SD: +/- 0.4, Median:2 IQR :1). Though group 3 and 4 had a higher mean for both accuracy and completeness, there was no significant scoring variation between the 4 question groups (Kruskal-Wallis test p:>0.05). However, statistical analysis for the different individual questions revealed a significant difference both for accuracy (p<0.001) and completeness (p<0.001). The questions which rated the highest for both accuracy and completeness were related to smoking, while the lowest rating was related to screening for malignancy and vaccinations especially in the context of immunosuppression and family planning. CONCLUSION: This is the first study to demonstrate the capability of an AI-based system to provide accurate and comprehensive answers to real-world patient queries in IBD. AI systems may serve as a useful adjunct for patients, in addition to standard of care in clinic and validated patient information resources. However, responses in specialist areas may deviate from evidence-based guidance and the replies need to give more firm advice.

Disease acceptance, but not perceived control, is uniquely associated with inflammatory bowel disease-related disability.

BACKGROUND AND AIMS: Disability, an important aspect of disease burden in patients with inflammatory bowel disease (IBD), has been suggested as a valuable clinical endpoint. We aimed to investigate how disease acceptance and perceived control, two psychological predictors of subjective health, are associated with IBD-related disability. METHODS: In this cross-sectional study, adult IBD patients from the University Hospitals Leuven received a survey with questions about clinical and demographic characteristics, disease acceptance and perceived control (Subjective Health Experience model questionnaire), and IBD-related disability (IBD Disk). Multiple linear regressions assessed predictors of IBD-related disability in the total sample and in the subgroups of patients in clinical remission or with active disease. RESULTS: In the total sample (N = 1250, 54.2% female, median [IQR] age 51 [39-61] years, 61.3% Crohn's disease, 34.9% active disease), adding the psychological predictors to the model resulted in an increased explained variance in IBD-related disability of 19% compared to a model with only demographic and clinical characteristics (R2adj 38% vs. 19%, p<.001). The increase in explained variance was higher for patients in clinical remission (ΔR2adj 20%, p<.001) compared to patients with active disease (ΔR2adj 10%, p<.001). Of these predictors, disease acceptance was most strongly associated with disability in the total sample (ß=-0.44, p<.001), as well as in both subgroups (ß=-0.47, p<.001 and ß=-0.31, p<.001 respectively). Perceived control was not significantly associated with disability when accounting for all other predictors. CONCLUSIONS: Disease acceptance is strongly associated with IBD-related disability, supporting further research into disease acceptance as a treatment target.

Crohn's Patient Serum Proteomics Reveals Response Signature for Infliximab but not Vedolizumab.

BACKGROUND: Crohn's disease is a chronic inflammatory bowel disease that affects the gastrointestinal tract. Common biologic families used to treat Crohn's are tumor necrosis factor (TNF)-α blockers (infliximab and adalimumab) and immune cell adhesion blockers (vedolizumab). Given their differing mechanisms of action, the ability to monitor response and predict treatment efficacy via easy-to-obtain blood draws remains an unmet need. METHODS: To investigate these gaps in knowledge, we leveraged 2 prospective cohorts (LOVE-CD, TAILORIX) and profiled their serum using high-dimensional isobaric-labeled proteomics before treatment and 6 weeks after treatment initiation with either vedolizumab or infliximab. RESULTS: The proportion of patients endoscopically responding to treatment was comparable among infliximab and vedolizumab cohorts; however, the impact of vedolizumab on patient sera was negligible. In contrast, infliximab treatment induced a robust response including increased blood-gas regulatory response proteins, and concomitant decreases in inflammation-related proteins. Further analysis comparing infliximab responders and nonresponders revealed a lingering innate immune enrichments in nonresponders and a unique protease regulation signature related to clotting cascades in responders. Lastly, using samples prior to infliximab treatment, we highlight serum protein biomarkers that potentially predict a positive response to infliximab treatment. CONCLUSIONS: These results will positively impact the determination of appropriate patient treatment and inform the selection of clinical trial outcome metrics.

Endoscopic and Histological Placebo Rates in Crohn's Disease Clinical Trials: A Systematic Review and Meta-analysis.

BACKGROUND: Precise estimates of placebo response rates help efficient clinical trial design. In this systematic review and meta-analysis, we assessed contemporary placebo endoscopic and histological response rates in Crohn's disease (CD) clinical trials. METHODS: MEDLINE, EMBASE, and Cochrane CENTRAL were searched from inception to April 2022 to identify placebo-controlled studies of pharmacological interventions for CD. Endoscopic response, remission, and mucosal healing rates for participants assigned to placebo in induction and maintenance studies were pooled using a random-effects model. Point estimates and associated 95% confidence intervals (CIs) were calculated. RESULTS: In total, 16 studies (11 induction, 3 maintenance, 2 induction and maintenance) that randomized 1646 participants to placebo were eligible. For induction trials, the pooled placebo endoscopic response, endoscopic remission, and mucosal healing rates in participants assigned to placebo were 13% (95% CI, 10-16; I2 = 14.1%; P = .14), 6% (95% CI, 3-11; I2 = 74.7%; P < .001), and 6% (95% CI, 4-9; I2 = 26.9%; P = .29), respectively. The pooled endoscopic remission rate in patients who were bio-naïve was 10% (95% CI, 4-23) compared with only 4% (95% CI, 3-7) in bio-experienced patients. For maintenance trials, the pooled endoscopic response, remission, and mucosal healing rates were 7% (95% CI, 1-31; I2 = 78.2%; P = .004), 11% (95% CI, 4-27; I2 = 70.8%; P = .06), and 7% (95% CI, 3-15; I2 = 29.7; P = .23), respectively. Only 3 trials assessed histological outcomes. CONCLUSIONS: Endoscopic placebo rates vary according to trial phase and prior biologic exposure. These contemporary data will serve to inform CD trial design, sample size calculation, and end point selection for future trials.

Dysbiosis and Associated Stool Features Improve Prediction of Response to Biological Therapy in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Dysbiosis of the gut microbiota is considered a key contributor to inflammatory bowel disease (IBD) etiology. Here, we investigated potential associations between microbiota composition and the outcomes to biological therapies. METHODS: The study prospectively recruited 296 patients with active IBD (203 with Crohn's disease, 93 with ulcerative colitis) initiating biological therapy. Quantitative microbiome profiles of pretreatment and posttreatment fecal samples were obtained combining flow cytometry with 16S amplicon sequencing. Therapeutic response was assessed by endoscopy, patient-reported outcomes, and changes in fecal calprotectin. The effect of therapy on microbiome variation was evaluated using constrained ordination methods. Prediction of therapy outcome was performed using logistic regression with 5-fold cross-validation. RESULTS: At baseline, 65.9% of patients carried the dysbiotic Bacteroides2 (Bact2) enterotype, with a significantly higher prevalence among patients with ileal involvement (76.8%). Microbiome variation was associated with the choice of biological therapy rather than with therapeutic outcome. Only anti-tumor necrosis factor-α treatment resulted in a microbiome shift away from Bact2, concomitant with an increase in microbial load and butyrogen abundances and a decrease in potentially opportunistic Veillonella. Remission rates for patients hosting Bact2 at baseline were significantly higher with anti-tumor necrosis factor-α than with vedolizumab (65.1% vs 35.2%). A prediction model, based on anthropometrics and clinical data, stool features (microbial load, moisture, and calprotectin), and Bact2 detection predicted treatment outcome with 73.9% accuracy for specific biological therapies. CONCLUSION: Fecal characterization based on microbial load, moisture content, calprotectin concentration, and enterotyping may aid in the therapeutic choice of biological therapy in IBD.

The assessment of segmental healing by the Modified Mayo Endoscopic Score (MMES) complements the prediction of long-term clinical outcomes in patients with ulcerative colitis.

BACKGROUND AND AIMS: Current endoscopic scoring systems for ulcerative colitis (UC) do not consider the extent of mucosal inflammation. The modified Mayo endoscopic score (MMES) was developed to detect segmental endoscopic improvement. We evaluated the ability of the MMES to predict long-term clinical outcomes and compared it to the widely used Mayo endoscopic subscore (MES). METHODS: Consecutive patients with moderate to severe UC starting biological therapy were enrolled between January 2014 and September 2017 in this prospective observational study. A clinical and endoscopic evaluation was performed at baseline and at week 8/14. A modified Mayo score was used to grade clinical activity, MES and MMES were used to evaluate endoscopic activity. Patients were divided into 3 groups according to the evolution of endoscopic activity, namely endoscopic improvement (MES ≤ 1), segmental endoscopic response only (MES > 1, but decrease in MMES ≥ 30%) or no endoscopic response (all others). Over the follow-up period clinical relapse-, discontinuation- and colectomy-free survival were assessed. RESULTS: A total of 150 patients were included (48% female, median age 42 years, median disease duration 7 years) with a median follow-up of 61 months. We identified 69 patients with endoscopic improvement, 27 with segmental endoscopic response and 54 without endoscopic response. Patients with segmental endoscopic response showed intermediate long-term clinical outcomes as compared to the other two groups (log rank p = 0.003 for clinical relapse-, and p < 0.001 for both discontinuation- and colectomy-free survival). CONCLUSIONS: The MMES exhibited a benefit in predicting long-term outcome in UC even though endoscopic improvement remains the strongest predictor.

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.

Crossing barriers: the burden of inflammatory bowel disease across Western Europe.

An estimated 2.5-3 million individuals (0.4%) in Europe are affected by inflammatory bowel disease (IBD). Whilst incidence rates for IBD are stabilising across Europe, the prevalence is rising and subsequently resulting in a significant cost to the healthcare system of an estimated 4.6-5.6 billion euros per year. Hospitalisation and surgical resection rates are generally on a downward trend, which is contrary to the rising cost of novel medication. This signifies a large part of healthcare cost and burden. Despite publicly funded healthcare systems in most European countries, there is still wide variation in how patients receive and/or pay for biologic medication. This review will provide an overview and discuss the different healthcare systems within Western Europe and the barriers that affect overall management of a changing IBD landscape, including differences to hospitalisation and surgical rates, access to medication and clinical trial participation and recruitment. This review will also discuss the importance of standardising IBD management to attain high-quality care for all patients with IBD.

Treatment of antibiotic refractory chronic pouchitis with JAK inhibitors and S1P receptor modulators: an ECCO CONFER Multicentre Case Series.

BACKGROUND AND AIMS: Data regarding effectiveness and safety of JAK inhibitors and S1P receptor modulators in antibiotic refractory chronic pouchitis (CARP) are lacking. METHODS: This ECCO-CONFER project retrospectively collected JAK inhibitors or S1P receptor modulators treatments for CARP with at least 3-months follow up. The outcomes included corticosteroid and antibiotics-free clinical response and remission at three and twelve months, trend in mPDAI, endoscopic PDAI, CRP and calprotectin. RESULTS: Seventeen treatments in 15 patients were collected. Previous pouchitis treatments included infliximab (5/15), adalimumab (4/15), vedolizumab (9/15), and ustekinumab (5/15). Pooling data on JAK inhibitors (8 tofacitinib, 1 filgotinib and 6 upadacitinib), after 3 months (T3), steroid and antibiotics-free clinical response was achieved in 53.3% (8/15), steroid and antibiotics-free clinical remission was achieved in 40% (6/15). Of the patients with at least 12 months of follow-up, steroid and antibiotics-free clinical response was achieved in 50% (3/6) and remission in one patient (16.7%), endoscopic response in 50% (3/6), endoscopic remission in 50% (3/6). Of the two ozanimod treatments at T3, steroid and antibiotics-free clinical response was achieved in one patient, without remission; both discontinued ozanimod before T12. No side effects reported. CONCLUSIONS: Small molecules may represent a suitable option for CARP refractory to multiple biologics, deserving further investigation.

The Safety, Tolerability, Pharmacokinetics and Clinical Efficacy of the NLRX1 agonist NX-13 in Active Ulcerative Colitis: Results of a Phase 1b Study.

BACKGROUND AND AIMS: NX-13 activation of NLRX1 reduces intracellular reactive oxygen species and decreases inflammation in animal models of colitis. A phase 1a trial demonstrated a gut-selective pharmacokinetic (PK) profile with good tolerability. This phase Ib study aimed to evaluate the safety, tolerability, and PK of NX-13 in patients with active ulcerative colitis (UC). METHODS: We conducted a multicenter, randomized, double-blinded, placebo-controlled trial of NX-13 in patients with active UC. Patients with a Mayo Clinic Score of 4-10 were randomly assigned (3:3:3:1 ratio) to three NX-13 oral dose groups (250mg Immediate Release (IR), 500mg IR, or 500mg Delayed Release (DR) or placebo) once daily for 4 weeks. Safety and PK were the primary and secondary objectives, respectively. RESULTS: Thirty-eight patients (11 females) were recruited and randomized to placebo (5), NX-13 250mg IR (11), NX-13 500mg IR (11), or NX-13 500mg DR (11) and received at least one dose. There were no Serious Adverse Events (SAEs) or deaths during the trial. One patient (500mg DR, 1/11) withdrew for worsening of UC and a second (500mg IR, 1/11) on the last day of treatment after a panic attack associated with atrial fibrillation. In the efficacy population (36 patients), clinical improvement in rectal bleeding and stool frequency scores relative to placebo were seen as early as week 2 and endoscopic response was seen at week 4. CONCLUSIONS: NX-13 was generally safe and well tolerated with early signs of rapid symptom and endoscopic improvement. This novel mechanism of action warrants further investigation. ClinicalTrials.gov: NCT04862741.

Baseline TREM-1 Whole Blood Gene Expression Does Not Predict Response to Adalimumab Treatment in Patients with Ulcerative Colitis or Crohn's Disease in the SERENE Studies.

BACKGROUND AND AIMS: This study assessed whether baseline triggering receptor expressed on myeloid cells [TREM-1] whole blood gene expression predicts response to anti-TNF therapy in patients with UC or CD. METHODS: TREM-1 whole blood gene expression was analysed by RNA sequencing [RNA-seq] in patients with moderately to severely active UC or CD treated with adalimumab in the Phase 3 SERENE-UC and SERENE-CD clinical trials. The predictive value of baseline TREM-1 expression was evaluated and compared according to endoscopic and clinical response vs non-response, and remission vs non-remission, at Weeks 8 and 52 [SERENE-UC], and Weeks 12 and 56 [SERENE-CD]. RESULTS: TREM-1 expression was analysed in 95 and 106 patients with UC and CD, respectively, receiving standard-dose adalimumab induction treatment. In SERENE-UC, baseline TREM-1 expression was not predictive of endoscopic response [p=0.48], endoscopic remission [p=0.53], clinical response [p=0.58] or clinical remission [p=0.79] at Week 8, or clinical response [p=0.60] at Week 52. However, an association was observed with endoscopic response [p=0.01], endoscopic remission [p=0.048], and clinical remission [p=0.04997] at Week 52. For SERENE-CD, baseline TREM-1 expression was not predictive of endoscopic response [p=0.56], endoscopic remission [p=0.33], clinical response [p=0.07], clinical remission [p=0.65] at Week 12, or endoscopic response [p=0.61], endoscopic remission [p=0.51], clinical response [p=0.62] or clinical remission [p=0.97] at Week 56. CONCLUSIONS: Baseline TREM-1 gene expression did not uniformly predict adalimumab response in SERENE clinical trials. Further research is needed to identify potential blood-based biomarkers predictive of response to anti-TNF therapy in patients with IBD.

Utility of the Serum-Based Endoscopic Healing Index in Monitoring Therapeutic Response in Ulcerative Colitis.

INTRODUCTION: Convenient and objective noninvasive tools to monitor therapy response in patients with ulcerative colitis (UC) are needed. This study aimed to evaluate the performance of the Endoscopic Healing Index [EHI], a serum test originally developed to monitor mucosal inflammation in Crohn's disease, in patients with UC. METHODS: Serum samples paired with endoscopic data from consecutive adult patients with UC initiating advanced therapy for active disease (Mayo Endoscopic Subscore [MES] > 1) were analyzed. EHI values were compared between groups showing endoscopic improvement, remission, and nonresponse, defined, respectively, as MES of ≤1, 0 and >1. We also assessed the association of EHI with longitudinal changes of MES and compared its performance with that of fecal calprotectin (FC) and C-reactive protein. RESULTS: A total of 127 patients provided 303 samples. Median EHI increased significantly with increasing MES score ( P < 0.001). Median EHI was significantly lower in patients with endoscopic remission or improvement compared with patients with no response ( P < 0.001, P < 0.001, respectively). A 10-point decrease in EHI was associated with 89% higher odds of 1-point decrease in MES ( P < 0.001). EHI detected MES 0-1 with an area under the receiver operating curve of 77.8%, which was comparable with that of FC and C-reactive protein (85.0% [ P = 0.076] and 70.6% [ P = 0.055], respectively). DISCUSSION: EHI values are significantly responsive to changes in mucosal inflammation, also in patients with UC, and can confirm and/or rule out mucosal inflammation with an almost similar accuracy to that of FC.