Ulcerative Colitis Patients In Clinical Remission Research Articles

Predictive Value of PHRI for Recurrence within One Year after UC Treatment: A Retrospective Study.

Aims/Background Accurate prediction of recurrence after treatment is crucial for controlling the progression and improving the prognosis of active ulcerative colitis (UC) patients. Previous studies have evaluated the therapeutic response in UC patients by assessing mucosal healing, using measures such as the Paddington International Virtual ChromoendoScopy Score (PICaSSO) and the PICaSSO Histological Remission Index (PHRI). The PHRI is effective for evaluating treatment response and disease control in UC patients, but its predictive value for short-term recurrence has not been reported in the literature. Therefore, this retrospective analysis of clinical data aims to explore the predictive value of the PHRI and provide a reference for improving the prognosis of UC patients. Methods Clinical data of UC patients in clinical remission admitted to our hospital from June 2017 to June 2023 were retrospectively collected. Patients were divided into the recurrence group and the non-recurrence group, based on whether they experienced recurrence during the one-year follow-up. Clinical data, laboratory test results, and PHRI scores were collected. Variables that showed statistically significant differences between groups in univariate analysis were included in multivariate logistic regression analysis. The predictive value of PHRI was analyzed with receiver operating characteristic (ROC) curve analysis. Results One hundred and two UC patients in the clinical remission stage were included in this study, and there were no cases of loss to follow-up. Among them, 36 patients (35.29%) experienced recurrence within the one-year follow-up, whereas 66 patients (64.71%) did not. Compared with the non-recurrence group, the recurrence group had a more number of cases with lesions in the left-sided colon and extensive colon, higher percentages of cases that were moderate or severe, and a significantly higher colonoscopy score (p < 0.05). Compared with the non-recurrence group, the PHRI score of the recurrence group was significantly higher (p < 0.001). Multivariate logistic regression analysis showed that that the lesion range (OR = 4.127, p = 0.005), disease severity (OR = 3.889, p = 0.019), colonoscopy score (OR = 6.128, p < 0.001), and PHRI score (OR = 5.466, p < 0.001) were independent risk factors for recurrence in UC patients. The results of ROC curve analysis showed that the area under the curve of the PHRI score in predicting the recurrence of UC patients was 0.838 (95% CI: 0.760-0.916). When the optimal cut-off value was 1 point, the sensitivity and specificity were the highest, which were 89.58% and 65.58%, respectively, indicating that PHRI score had good predictive value. Conclusion The lesion extent, disease severity, endoscopic score, and PHRI score are associated with recurrence within one year in UC patients in the clinical remission stage, and the PHRI score has good predictive value.

Histologic healing and clinical outcomes in ulcerative colitis.

Growing evidence suggests histologic healing (HH) improves clinical outcomes in ulcerative colitis (UC) patients beyond endoscopic healing (EH). We hypothesize that HH is associated with better clinical outcomes in Asian UC patients, for whom data is lacking. We performed a retrospective study of UC patients in clinical remission (CR) with a follow-up colonoscopy and minimum 1-year follow-up post-colonoscopy. Primary outcome was clinical relapse (CRL), defined as either a Simple Clinical Colitis Activity Index score of > 2, medication escalation, hospitalization or colectomy. Predictors of CRL and HH were assessed. One hundred patients were included with a median follow-up of 22 months. At index colonoscopy, 80 patients were in EH. On follow-up, 41 patients experienced CRL. Of 80 patients in EH, 34 (42.5%) had persistent histologic activity (Nancy Index ≥ 2) and 29 (36.3%) relapsed during the follow-up period. Amongst patients in CR and EH, those with HH had lower CRL rate (26.1% vs. 50.0%, P= 0.028) and longer CRL-free survival (mean 46.1 months vs. 31.5 months, P= 0.015) than those with persistent histologic activity. On bivariable analysis of 100 patients in CR, HH, and Mayo endoscopic score (MES) of 0 were significantly associated with lower risk of CRL. On multivariable analysis, only MES 0 remained predictive of lower CRL risk. Above and beyond CR and EH, achieving HH improves clinical outcomes in Asian UC patients. However, HH may not confer incremental benefit if MES 0 has been achieved. Further prospective studies evaluating the benefit of histologically guided therapeutic decisions are needed.

Efficacy of Beclomethasone Dipropionate in Lowering Fecal Calprotectin Levels in Patients with Ulcerative Colitis in Clinical Remission and at Risk of Relapse: The Becalcu Randomized, Controlled Trial

Introduction: Identifying novel treatment strategies for patients with ulcerative colitis (UC) and at risk of relapse is critical. The objective of this study was to assess the efficacy of beclomethasone dipropionate (BDP) in lowering fecal calprotectin (FC) levels in UC patients in clinical remission and at risk of relapse. Methods: This multicenter study comprised a double-blind, randomized, placebo-controlled phase (part I) and an open-label, non-randomized phase (part II). Eligible participants with UC in clinical remission treated with 5-aminosalicylic acid and with FC levels ≥250 μg/g were randomized to receive 5 mg/day of BDP or placebo for 4 weeks (part I). At week 5, patients with FC ≥100 μg/g were treated with 5 mg/day of BDP for 4 weeks (part II), and FC levels were tested at week 9. Results: Forty-three patients were randomized: 22 received BDP (group A) and 21 placebo (group B). At week 4, 13 patients (59.1%) in group A and 3 (17.6%) in group B had FC levels <100 μg/g (p value = 0.010). In the double-blind phase of the study, no patient relapsed in group A and 4 in group B (p value = 0.049). Both treatment groups showed a favorable safety profile, with the most common adverse events being gastrointestinal disorders. Conclusion: In this multicenter, randomized clinical trial including patients with UC in clinical remission but with elevated FC, BDP was efficacious in reducing FC and well-tolerated.

Efficacy of Dose Escalation of Oral 5-Aminosalicylic Acid for Ulcerative Colitis With a Mayo Endoscopic Subscore of 1: An Open Label Randomized Controlled Trial.

Endoscopic healing is generally defined as Mayo endoscopic subscore (MES) ≤1 in ulcerative colitis (UC). However, patients with an MES of 1 are at higher relapse risk than those with an MES of 0. This study evaluated the therapeutic efficacy of proactive dose escalation of oral 5-aminosalicylic acid (5-ASA) in UC patients with an MES of 1. An open-label, randomized controlled trial was conducted in 5 hospitals between 2018 and 2022. Ulcerative colitis patients in clinical remission under oral 5-ASA therapy and diagnosed as having an MES of 1 were enrolled. Patients receiving maintenance therapy other than 5-ASA and immunomodulator were excluded. Patients were randomly assigned in a 1:1 ratio to receive either a dose-escalated (intervention) or constant dose (control) of 5-ASA. Concomitant immunomodulator was used as the stratification factor in the randomization. The primary end point was relapse within 1 year. The subgroup analysis was stratified for the use of immunomodulators. The full analysis set included 79 patients (39 intervention and 40 control). Immunomodulators were used in 20 (25.3%) patients. Relapse was less in the intervention group (15.4%) than the control group (37.5%; P = .026). In the subgroup with concomitant immunomodulators, relapse was also less in the intervention group (10.0%) than the control group (70.0%; P = .020). In patients without immunomodulators, the difference was not significant between 2 groups (intervention, 17.2%; control, 26.7%; P = .53). Dose escalation of 5-ASA reduced relapse within 1 year in UC patients in clinical remission with an MES of 1.

P356 Long-term outcome of UC patients in clinical remission with different level of mucosal activity: real world, retrospective, multicontinental study

Abstract Background In contrast to the increasingly rigorous endpoints of clinical trials of ulcerative colitis (UC), Mayo endoscopic score (MES) ≤ 1 is mostly set as target during clinical follow-up, but long-term outcomes may differ according to different level of healing. Therefore, our study aimed to compare the long-term outcomes of UC patients in clinical remission with different MES and UCEIS scores in real-life condition. Methods UC patients in clinical remission (defined by pMayo&amp;lt;2 with no rectal bleeding) who underwent colonoscopy between 2016-2020 were consecutively enrolled in this multicenter retrospective study. Mayo and UCEIS endoscopic scores were evaluated and clinical and demographic data were collected at baseline. Clinical flare, colectomy, hospitalization and treatment modifications were recorded during at least 3 year of follow-up. Primary outcome was the clinical flare, while secondary outcomes were hospitalization, colectomy, new biological initiation and biological dose escalation during follow-up. Outcomes were compared with Log-rank test and survival characteristics were plotted. Results In total, 156 UC patients were enrolled with a median age of 46.0 (IQR 35.5-58.0), while male/female ratio was 49.4 % (Table 1.). Near to half of the patients (44.9%) had MES&amp;gt;0 endoscopic activity at baseline. Non zero baseline MES (Figure 1.; p = 0.002; MES 0 vs 1 p = 0.004) and UCEIS (p &amp;lt; 0.001; UCEIS 0 vs. 1 p = 0.016) scores were associated with higher rate of clinical flare. Higher baseline MES (p = 0.042) and UCEIS (p = 0.008) scores were coupled with increased risk of hospitalization. Colectomy rates were low. Increased baseline UCEIS (p = 0.003), but not MES score was coupled with new biological treatment initiation, while only UCEIS score was associated with biological treatment intensification (&amp;gt;4; p = 0.008). Conclusion Our study suggests differentiating between complete MH from MES 1 as long-term outcomes were more favorable in case of lower endoscopic scores. Consequently, targeting complete MH should be considered to achieve deep remission and disease clearance.

P412 Faecal Calprotectin as a predictor of endoscopic and histologic remission in patients with Ulcerative Colitis

Abstract Background Faecal calprotectin (FCP) is a reliable surrogate marker for disease activity in ulcerative colitis (UC). However, there are no consensus cut-off values for histoendoscopic remission. The aim of the study is to correlate FCP with Mayo Endoscopic Score (MES) and histological disease activity (Geboes score) of UC patients in clinical remission. Methods We performed a prospective study including adult UC patients at the McGill IBD Center between 2013 and 2017. Patients in clinical remission (partial Mayo score ≤2) or disease relapse, undergoing endoscopy for disease activity or dysplasia surveillance, were enrolled. Before bowel preparation, FCP was collected. MES was documented during colonoscopy. Biopsies were taken throughout the colon and histological activity was assessed using Geboes score (GS) by a blinded expert gastrointestinal pathologist. Results The study included 253 patients, of which 117 (46%) were male with a mean age of 38.2 years (standard deviation [SD] ± 24.8). 46% of the patients had pancolitis at the time of colonoscopy. 5-aminosalicylate were used by 68.4% of patients while 20.9% were on immunomodulators, 19% on biologics and 0.4% on small molecules as treatment. Regarding endoscopic correlation, it showed that an FCP ≥ 200 μg/g predicts MES &amp;gt; 1 despite clinical remission, yielding sensitivity of 59% and specificity of 74%. A FCP ≥ 123 predicts MES &amp;gt; 0 despite clinical remission (58% sensitivity and 70% specificity), also aiding to differentiate MES 0 from MES 1 (61% sensitivity and 70% specificity). As to histologic correlation, a FCP ≥ 80 μg/g identified histological disease activity using Geboes criteria (GS score &amp;gt; 3.1) in patients with clinical remission, yielding 64.7% sensitivity, 58.7% specificity and 77% positive predictive value (Figure 1). When using a GS score threshold of &amp;gt; 2, a cut-off value of FCP ≥ 50 μg/g, appears to be the most clinically relevant to identify patients in clinical remission who continue to have active histologic inflammation, with an 49.6% sensitivity, 41.6% specificity and 40% positive predict value. Results are summarized in Table 1. Conclusion FCP correlates very well with endoscopic and histologic disease activity and can be used as a surrogate marker for disease activity. Our study prospectively demonstrated the optimal cut-off values helping to discriminate endoscopic healing and histologic remission.

Healing of the epithelial barrier in the ileum is superior to endoscopic and histologic remission for predicting major adverse outcomes in ulcerative colitis.

Achieving endoscopic remission is a key therapeutic goal in patients with ulcerative colitis (UC) that is associated with favorable long-term disease outcomes. Here, we prospectively compared the predictive value of endoscopic and/or histologic remission against ileal barrier healing for predicting long-term disease behavior in a large cohort of UC patients in clinical remission. At baseline, UC patients in clinical remission underwent ileocolonoscopy with assessment of ileal barrier function by confocal endomicroscopy. Endoscopic and histologic disease activity and ileal barrier healing were scored using validated scores. During subsequent follow-up (FU), patients were closely monitored for clinical disease activity and occurrence of major adverse outcomes (MAO) defined as the following: disease relapse; UC-related hospitalization; UC-related surgery; necessity for initiation or dose escalation of systemic steroids, immunosuppressants, small molecules or biological therapy. Of the 73 UC patients included, 67% experienced MAO during a mean FU of 25 months. The probability of MAO-free survival was significantly higher in UC patients with endoscopic and/or histologic remission compared to patients with endoscopically and/or histologically active disease. Ileal barrier healing on endomicroscopy was highly accurate for predicting the further course of UC and outcompeted endoscopic and histologic remission for predicting MAO-free survival. Ileal barrier healing in clinically remittent UC patients can accurately predict future MAO development and is superior in its predictive capabilities than endoscopic and histologic remission. Ileal barrier healing therefore represents a novel and superior surrogate parameter for stratification of UC patients according to their risk for development of complicated disease behavior. https://classic.clinicaltrials.gov/ct2/show/NCT05157750, identifier NCT05157750.

Modificación de la dosis de mesalazina en función de los niveles de calprotectina fecal en pacientes con colitis ulcerosa en remisión clínica

BackgroundFaecal calprotectin (FC) shows an excellent correlation with endoscopic and histological activity of ulcerative colitis (UC) and it is the best predictor of clinical relapse. Our aim was to evaluate the usefulness of modifying the dose of mesalazine based on FC levels, in clinical practice. MethodsRetrospective, single-centre study in UC patients in clinical remission while treated with mesalazine which dosage was decreased (DOWN) or increased (UP) according to FC levels. The main endpoint was the long-term maintenance of clinical remission. ResultsA total of 56 patients were included (39 DOWN, 17 UP). In the DOWN group, the median baseline dose of mesalazine was 3.6g/day and the median baseline FC was 36μg/g. After a median follow-up of 22 months, 28% required rescue therapy. The cumulative relapse-free survival after tapering was 91% and 82% at 12 and 24 months, respectively. In the UP group, the median baseline dose of mesalazine was 2.4g/day, with a median baseline FC of 524μg/g. After a median follow-up of 12 months, 29% required rescue therapy. The cumulative relapse-free survival after dose increase was 86% and 72% at 12 and 24 months, respectively. ConclusionsMesalazine dose modification based on FC monitoring seems to be a safe strategy in patients with UC in clinical remission, with a probability of clinical relapse around 20% at two years.

Switching from VEDOlizumab intravenous to subcutaneous formulation in ulcerative colitis patients in clinical remission: The SVEDO Study, an IG-IBD study

BackgroundThe administration of biological drugs in inflammatory bowel diseases (IBD) is increasingly moving from intravenous to subcutaneous formulations. AimsTo evaluate the efficacy and safety of vedolizumab subcutaneous administration after switching from intravenous administration in ulcerative colitis (UC) patients in corticosteroid-free clinical remission. MethodsAn observational, multicentre, prospective study was conducted by the Italian Group for the study of IBD (IG-IBD). UC patients in clinical remission (pMAYO < 2) not receiving steroids for > 8 months before the switch, and with at least 6 months of follow-up were included. Switch from intravenous to subcutaneous vedolizumab was defined as successful in patients not experiencing a disease flare (pMAYO ≥ 2) or needing oral steroids or stopping subcutaneous vedolizumab during the 6 months of follow-up after the switch. ResultsOverall, 168 patients were included. The switch was a success in 134 patients (79.8%). Vedolizumab retention rate was 88.7% at month six. C-reactive protein and faecal calprotectin values did not change after the switch (p = 0.07 and p = 0.28, respectively). Ten of the 19 patients who stopped subcutaneous formulation switched back to intravenous formulation recapturing clinical remission in 80%. Side effects were observed in 22 patients (13.1%). ConclusionEffectiveness of switching from intravenous to subcutaneous vedolizumab formulation in UC patients in steroid-free clinical remission is confirmed in a real-world setting.

A Mediterranean Diet Pattern Improves Intestinal Inflammation Concomitant with Reshaping of the Bacteriome in Ulcerative Colitis: A Randomised Controlled Trial.

Dietary patterns are important in managing ulcerative colitis [UC], given their influence on gut microbiome-host symbiosis and inflammation. We investigated whether the Mediterranean Diet Pattern [MDP] vs the Canadian Habitual Diet Pattern [CHD] would affect disease activity, inflammation, and the gut microbiome in patients with quiescent UC. We performed a prospective, randomised, controlled trial in adults [65% female; median age 47 years] with quiescent UC in an outpatient setting from 2017 to 2021. Participants were randomised to an MDP [n = 15] or CHD [n = 13] for 12 weeks. Disease activity [Simple Clinical Colitis Activity Index] and faecal calprotectin [FC] were measured at baseline and week 12. Stool samples were analysed by 16S rRNA gene amplicon sequencing. The diet was well tolerated by the MDP group. At week 12, 75% [9/12] of participants in the CHD had an FC >100 μg/g, vs 20% [3/15] of participants in the MDP group. The MDP group had higher levels of total faecal short chain fatty acids [SCFAs] [p = 0.01], acetic acid [p = 0.03], and butyric acid [p = 0.03] compared with the CHD. Furthermore, the MDP induced alterations in microbial species associated with a protective role in colitis [Alistipes finegoldii and Flavonifractor plautii], as well as the production of SCFAs [Ruminococcus bromii]. An MDP induces gut microbiome alterations associated with the maintenance of clinical remission and reduced FC in patients with quiescent UC. The data support that the MDP is a sustainable diet pattern that could be recommended as a maintenance diet and adjunctive therapy for UC patients in clinical remission. ClinicalTrials.gov no: NCT0305371.

P418 Dose escalation of oral 5-aminosalicylic acid for ulcerative colitis with Mayo endoscopic subscore of one improves long-term prognosis: a one-year multicentre, open-label, randomized controlled trial.

Abstract Background Endoscopic healing, one of the treatment targets for ulcerative colitis (UC), is commonly defined as Mayo endoscopic sub-score (MES) ≤1. Furthermore, patients in whom MES of 0 is achieved are at a lower risk of relapse than those with MES of 1. However, it is unclarified whether the therapeutic intervention of dose escalation of oral 5-aminosalicylic acid (5-ASA) improves the prognosis of UC patients in clinical remission with MES of 1. Methods A multicentre, open-label, randomized, controlled trial was conducted among 5 hospitals in Japan from March 2018 to June 2022. Patients with UC, aged 16 years or older, treated with 5-ASA, in clinical remission and confirmed MES of 1 were enrolled. Patients receiving maintenance therapy other than oral 5-ASA and thiopurine (e.g., topical therapy, biologics) were excluded. Patients were randomly assigned to either the therapeutic intervention group (increased the dose of 5-ASA) or the control group (without any intervention). Concomitant use of immunomodulator (IM) was used for the stratification factor in the randomization. The primary endpoint was clinical relapse within one year. Relapse was defined as both (1) pMayo ≥3 or rectal bleeding sub-score ≥1, and (2) addition of any induction treatments for UC including topical agents. Predictive factors for relapse and adverse events (AEs) were investigated as the secondary outcomes. The predictive factors were explored in the multivariable Cox regression analysis. Results Eighty-one patients were enrolled and randomly assigned into the therapeutic intervention or the control group, and two patients were excluded due to important protocol violations after the randomization. Finally, 79 patients (n=39; therapeutic intervention, n=40; control) were included in the full analysis set (FAS). In the FAS, 46 (58.2%) patients were male, and 20 (25.3%) patients were treated with IMs. The relapse within one year was less in the therapeutic intervention group (6/39; 15.4%) than the control group (15/40; 37.5%), significantly (P =0.026) (Fig.1). In the exploratory analysis for the predictors, concomitant use of IM was associated with relapse (hazard ratio, 2.52; 95% confidence interval, 1.04-6.12, P =0.041). There were three AEs in the therapeutic intervention group. Two patients complained of nausea, and the other complained of diarrhea and melena. All the AEs were improved after turning back the treatment to that before the intervention. Fig. 1. The proportion of patients relapsed within one year in the full analysis set (primary analysis). Conclusion The dose escalation of oral 5-ASA reduced the relapse within one year in UC patients in clinical remission with MES of 1.

P819 Histologic activity and clinical outcomes in Ulcerative Colitis

Abstract Background Microscopic inflammation persisting in ulcerative colitis (UC) patients with endoscopic remission (ER) may be associated with a higher risk of clinical relapse (CRL). Growing evidence suggests histologic remission (HR) improves clinical outcomes. Data from Asian UC patients is lacking. We hypothesize that achieving HR is associated with better clinical outcomes in Asian UC patients. Methods We performed a single-centre retrospective cohort study of UC patients in clinical remission (CR) who had a follow-up (‘index’) colonoscopy and minimum one-year follow-up post-colonoscopy. CR was defined as Simple Clinical Colitis Activity Index (SCCAI) ≤2. ER was defined as Mayo Endoscopic Sub-Score (MES) ≤1 at index colonoscopy. HR was defined as Nancy Index ≤1 at index colonoscopy. CRL was defined as either SCCAI&amp;gt;2 (sub-score &amp;gt;1 for stool frequency or rectal bleeding), medication escalation for active disease, hospitalisation for UC relapse or colectomy for refractory UC. Kaplan-Meier survival analysis was performed to evaluate clinical relapse-free survival post-colonoscopy. Univariate and multivariate regression analyses were performed to assess predictors of CRL. Results 169 consecutive UC patients who had undergone colonoscopy from 1 Jan 2000 to 30 Jul 2019 were assessed for eligibility. 100 patients were included with a median follow-up of 22 months. At index colonoscopy, 80 patients (80%) were in ER, with 20 patients having persistent endoscopic activity (Table 1). On follow-up, 41 patients (41%) experienced CRL, with 59 remaining in CR. Of 80 patients in ER, 34 (42.5%) had persistent histologic activity (Nancy Index ≥2) and 29 (36.3%) relapsed during the follow-up period (Table 2). Amongst patients in CR and ER, those with HR had lower CRL rate (26.1% vs 50%, p=.028) and longer clinical relapse-free survival (mean 46.1 vs 31.5 months, p=.015) than those with persistent histologic activity (Figure 1). On univariate and multivariate analysis of 100 patients in CR, HR was significantly associated with lower risk of CRL (Table 3). Conclusion Above and beyond CR and ER, achieving HR improves clinical outcomes in Asian UC patients. Further prospective studies evaluating the benefit of histologically guided therapeutic decisions are needed.

Dietary beliefs and information resources of ulcerative colitis patients in clinical remission: A cross-sectional survey in Taiwan.

Despite the lack of evidence for the benefits of dietary restrictions for ulcerative colitis (UC), the majority of patients with UC restrict their diets to avoid relapses. Few studies have examined information resources that affect patients' dietary beliefs or practices, but none have investigated UC patients in clinical remission from Asia. This survey investigated the dietary beliefs, practices, and information resources of Taiwanese UC patients in clinical remission. A self-reported questionnaire was administered. Fifty UC patients in clinical remission (defined based on having a 2-item patient-reported outcome score of ≤1 with no rectal bleeding for ≥90 days) were recruited from National Taiwan University Hospital between September 2017 and March 2018. In total, 22 patients (45.8%) believed diet to be the initiating factor for UC, and 48.0% of patients believed diet has ever triggered relapses. Forty-two patients (85.7%) avoided specific foods to prevent a relapse. Spicy foods were the most avoided foods (75.5%), following by alcohol (69.4%), carbonated beverages (63.3%), milk or milk products (59.2%), and fatty foods (59.2%). The patients' information resources for dietary beliefs and practices consisted mainly of their own experience. Approximately one-third of the patients have avoided the same menu with their family or avoided outdoor dining to prevent UC relapses. This is the first dietary belief survey focusing on clinical remission UC patients from Asia. Most clinical remission UC patients spontaneously avoided specific foods based on their own experiences. Dietary restrictions may negatively affect patients' social lives. Further dietary counseling is necessary to minimize the possible negative impacts on UC patients in clinical remission.

Anti-Inflammatory Diet Prevents Subclinical Colonic Inflammation and Alters Metabolomic Profile of Ulcerative Colitis Patients in Clinical Remission.

A relationship between ulcerative colitis (UC) and diet has been shown in epidemiological and experimental studies. In a 6-month, open-label, randomized, placebo-controlled trial, adult UC patients in clinical remission were randomized to either an “Anti-inflammatory Diet (AID)” or “Canada’s Food Guide (CFG)”. Menu plans in the AID were designed to increase the dietary intake of dietary fiber, probiotics, antioxidants, and omega-3 fatty acids and to decrease the intake of red meat, processed meat, and added sugar. Stool was collected for fecal calprotectin (FCP) and microbial analysis. Metabolomic analysis was performed on urine, serum, and stool samples at the baseline and study endpoint. In this study, 53 patients were randomized. Five (19.2%) patients in the AID and 8 (29.6%) patients in the CFG experienced a clinical relapse. The subclinical response to the intervention (defined as FCP < 150 µg/g at the endpoint) was significantly higher in the AID group (69.2 vs. 37.0%, p = 0.02). The patients in the AID group had an increased intake of zinc, phosphorus, selenium, yogurt, and seafood versus the control group. Adherence to the AID was associated with significant changes in the metabolome, with decreased fecal acetone and xanthine levels along with increased fecal taurine and urinary carnosine and p-hydroxybenzoic acid levels. The AID subjects also had increases in fecal Bifidobacteriaceae, Lachnospiraceae, and Ruminococcaceae. In this study, we found thatdietary modifications involving the increased intake of anti-inflammatory foods combined with a decreased intake of pro-inflammatory foods were associated with metabolic and microbial changes in UC patients in clinical remission and were effective in preventing subclinical inflammation.

P221 Association between Irritable Bowel Syndrome-type symptoms and Ulcerative Colitis: is it real?

Abstract Background The origin of gastrointestinal symptoms compatible with irritable bowel syndrome (IBS) in patients with inflammatory bowel disease in remission is a challenge. Our aim was to prospectively determine the relation of IBS symptoms with calprotectin levels (FC), endoscopic Mayo score and histologic findings, in patients with ulcerative colitis (UC) in clinical remission. Methods Patient recruitment was between January – March of 2020 and November of 2020 - August of 2021 and included consecutive UC patients in clinical remission and scheduled for a colonoscopy. Clinical remission was defined by a stool frequency ≤3/day with no bleeding, ulcerative colitis activity index &amp;lt;4 and serum C-reactive protein lower than 1mg/dL. Exclusion criteria were therapeutic with corticosteroids over the prior 6 months or initiation of biological agents in the last 6 months. IBS diagnosis was evaluated by Roma IV criteria (IBS-like group). FC level was assessed before colonoscopy and during the exam Mayo endoscopy subscore was applied and random biopsies of all segments of colon and rectum were made to achieve histologic activity using Geboes index. This study was approved by Centro Hospitalar e Universitário de Coimbra Ethics Committee. Results A total of 106 patients (50% women; mean age 51 years ±14.8) were included. The mean of disease duration was 15.7 years (±9.06) and 13 of them (12.3%) had proctitis, 64 (60%) left-sided colitis and 29 (27.4%) extensive colitis. Regarding disease activity: mean FC was 189.48mg/Kg (±382), endoscopic Mayo score lower than 1 was found in 63 patients (59.4%) and Geboes index lower than 1.1 was found in 66 patients (62.3%). Rome IV criteria for IBS were fulfilled by 29 patients (27.4%). The IBS-like group showed FC levels significantly higher (303±483mg/Kg vs. 139±319mg/Kg; P&amp;lt;0.05), with greater histologic activity (Geboes index &amp;gt;1.1 in 65,5% vs. 27.3%, P&amp;lt;0.05). Besides, in the same group (IBS-like group), Mayo endoscopy subscore was numerical higher but with no statistical significancy (subscore ≥1: 55.2% vs. 36.4%; P&amp;gt;0.05). Conclusion IBS-like symptoms are common in patients with UC considered to be in clinical remission. Higher levels of FC and histological activity support the idea of the presence of subclinical inflammation rather than coexistent IBS.

Effects of Xylo-Oligosaccharide on the Gut Microbiota of Patients With Ulcerative Colitis in Clinical Remission.

Gut microbiota dysbiosis is closely associated with ulcerative colitis (UC). Prebiotic therapy is a potential approach for UC management especially remission maintaining. Xylo-oligosaccharide (XOS) is an efficient prebiotic with proven health benefits and few side effects. However, the effects of XOS on the gut microbiota of patients with UC have not been investigated previously. The aim of this study was to evaluate the prebiotic effects of XOS on the fecal microbiota of patients with UC in clinical remission using an in vitro fermentation model. Five patients with UC in clinical remission and five healthy volunteers were enrolled in this study. Fresh fecal samples of UC patients were diluted and inoculated in yeast extract, casitone and fatty acid (YCFA) medium alone or with XOS. After fermentation for 48 h, samples were collected for 16S rDNA sequencing to investigate the gut microbiota composition. Differences in the gut microbiota between healthy volunteers and UC patients in clinical remission were detected using original fecal samples. Subsequently, the differences between the YCFA medium alone or with XOS samples were analyzed to illustrate the effects of XOS on the gut microbiota of UC patients. In both principal coordinate analysis (PCoA) and principal component analysis (PCA), the fecal samples of UC patients differed from those of healthy volunteers. Linear discriminant analysis effect size (LEfSe) analysis revealed that the relative abundances of g_Roseburia and g_Lachnospiraceae_ND3007_group were higher in healthy volunteers than in UC patients, while o_Lactobacillales abundance showed the opposite trend (P < 0.05). Wilcoxon rank-sum test bar plot showed that the abundances of g_Eubacterium_halli_group and g_Lachnospiraceae_ND3007_group were higher in the healthy volunteers than in the UC patients (P < 0.05). In addition, in UC patients, the Wilcoxon rank-sum test showed that XOS fermentation promoted the growth of bacterial groups including g_Roseburia, g_Bifidobacterium, and g_Lactobacillus, which is beneficial for recovery of intestinal diseases. These results suggest that XOS can relieve dysbiosis in the feces of UC patients in clinical remission and thus represent a potential prebiotic material for maintaining remission.

Deoxycholic acid delays the wound healing of colonic epithelial cells via transmembrane G-protein-coupled receptor 5.

Efficient intestinal wound healing is essential for good prognoses of ulcerative colitis (UC). Although bile acids and the transmembrane G-protein-coupled receptor (TGR) 5 have been reported to affect wound healing in intestinal epithelial cells, the detailed underlying mechanisms are unclear. Here, we investigated the role of TGR5 in wound healing in the context of colonic epithelial cells in the presence of bile acids. The expression of TGR5 in the colonic epithelium of both a dextran sulfate sodium (DSS)-induced colitis mouse model (recovery phase), and UC patients in clinical remission, was evaluated. Young adult mouse colonic epithelial (YAMC) cells were then used to evaluate wound healing after treatment with deoxycholic acid (DCA); TGR5 was silenced in YAMC cells via shRNA-transfection, and a wound-healing assay in the presence of DCA was performed. Furthermore, we investigated the role of the activation of AKT in the context of wound healing. The expression of TGR5 was decreased in the colonic epithelium of both mice with DSS-induced colitis and UC patients. Additionally, DCA significantly delayed wound healing in YAMC cells but not in TGR5 silenced ones. Of note, the DCA-induced activation of AKT signaling in YAMC cells was inhibited by TGR5 silencing, and AKT inhibitors prevented the wound healing delay induced by DCA. Overall, we show that DCA delays wound healing in the context of colonic epithelial cells through AKT activation. These results may support the development of new therapeutic approaches for epithelial regeneration in UC.

Determining the usefulness of Capsule Scoring of Ulcerative Colitis in predicting relapse of inactive ulcerative colitis.

The usefulness of second-generation colon capsule endoscopy (CCE2) in ulcerative colitis (UC), especially in clinically inactive patients, has been reported. Capsule Scoring of Ulcerative Colitis (CSUC) was developed as a severity index for UC. We aimed to determine whether CSUC is useful for predicting relapse during clinical remission. Forty-one UC patients in clinical remission who underwent CCE2 were prospectively registered from April 2016 to August 2019. Patients' CSUC score was obtained; those with subsequent relapse were followed up retrospectively. The correlation of CSUC with white blood cell count, platelet count, albumin, C-reactive protein, fecal calprotectin and fecal lactoferrin levels, and fecal immunochemical test results was evaluated; their predictive values for future relapse were compared. The correlations of CSUC with white blood cell, platelet, albumin, C-reactive protein, fecal calprotectin, fecal immunochemical test, and fecal lactoferrin values were rs =0.13, 0.27, -0.25, 0.15, 0.50, 0.43, and 0.50, respectively. CSUC was higher in 12 patients who relapsed within 1year than in 29 patients who remained in clinical remission (2.83±1.95 vs 0.72±1.00, P<0.01). Receiver operator characteristic curve analysis showed that CSUC ≥1 was a predictor of relapse (area under the curve of 0.82, sensitivity of 83.3%, specificity of 58.6%) and maybe superior to fecal biomarkers. In the univariate analysis, patients with CSUC of 0 had a lower relapse rate than those with CSUC of ≧1 (P=0.03, log-rank test). After analyzing patients who underwent CCE2 within 6months after the successful induction treatment, results showed that those with CSUC of ≤1 remained in clinical remission for a year. CSUC predicts relapse within 1year in UC patients in clinical remission, especially when used 6months after induction treatment.

Clinical Significance of Residual Nonrectal Inflammation in Ulcerative Colitis Patients in Clinical Remission

Background/AimsThe treatment goal of ulcerative colitis (UC) has been changed to achieve endoscopic remission (ER). However, there is insufficient clinical evidence to determine whether a step-up treatment should be performed to achieve ER in clinical remission (CR) without ER, and there are inadequate data on the need to consider the distribution and severity of residual inflammation. This retrospective study aimed to evaluate the prognostic significance of the distribution and severity of residual inflammation in UC patients in CR.MethodsA total of 131 UC patients in CR who underwent endoscopic evaluation for more than three times between January 2000 and December 2018 were reviewed. The patients were allocated by the endoscopic healing state and the distribution of inflammation to ER (n=31, 23.7%), residual nonrectal inflammation with patchy distribution (NRI) (n=17, 13.0%) or residual rectal involvement with continuous or patchy distribution (RI) (n=83, 63.3%) groups. We reviewed clinical characteristics, endoscopic findings, and factors associated with poor outcome-free survival (PFS).ResultsIn UC patients in CR, PFS was significantly higher in the ER and NRI groups than in the RI group (p=0.003). Patients in the ER and NRI groups had similar PFS (p=0.647). Cox proportional hazard model showed only RI (hazard ratio, 5.76; p=0.027) was associated with a higher risk of poor outcome.ConclusionsWe suggest that escalation of treatment modalities may be selectively performed in consideration of the residual mucosal inflammation pattern, even if ER has not been achieved, in UC patients with CR. (Gut Liver 2021;15-409)

What is the appropriate cut-off value of CRP to predict endoscopic remission in patients with ulcerative colitis in clinical remission?

Noninvasive markers for predicting endoscopic remission (ER) in patients with ulcerative colitis (UC) who are in clinical remission (CR) are important for the determination of appropriate treatment modality. C-reactive protein (CRP) is a surrogate marker for assessing disease activity, albeit with a low sensitivity and specificity when the cut-off value is 0.3 or 0.5 mg/dL, which is usually considered normal. The CRP test has been improved, and even fine values within the normal range can be measured. The aim of this study was to determine the appropriate cut-off value of CRP below 0.3 mg/dL for the prediction of ER in UC patients with CR. A total of 132 patients who underwent endoscopic evaluation during CR were retrospectively reviewed. Clinical and endoscopic activity was measured using a simple clinical colitis activity index (SCCAI) and Mayo endoscopic subscore (MES). ER was defined as MES 0 or 1. In UC patients in CR, the CRP level was significantly lower in ER (0.05, 0.03-2.57) vs. non-ER (0.14, 0.03-2.81) (p < 0.001). The CRP value predicted ER [area under the curve (AUC = 0.710)] with a sensitivity of 71.4% and a specificity of 71.7% at a cut-off value of 0.09 mg/dL. In contrast, the value of normal CRP (< 0.3 mg/dL) did not show sufficient predictive value (sensitivity, 27.3%; and specificity, 90.9%). In UC patients in CR, it may be helpful to lower the CRP cut-off value that predict ER other than 0.3 mg/dL, which is usually considered normal.