Remission In Crohn's Disease Research Articles

Preliminary results from a multicenter, randomized trial using fecal microbial transplantation to induce remission in patients with mild to moderate Crohn’s disease

Introduction: Fecal microbial transplantation (FMT) has shown promise at inducing remission in ulcerative colitis. This study is the first of its kind to evaluate the efficacy and safety of FMT at inducing remission in Crohn’s disease (CD). Methods: This double-blind, placebo-controlled trial was conducted in three Canadian academic centers; randomized patients with mild to moderate CD received FMT or placebo. The first treatment was administered by colonoscopy followed by weekly fecal capsules for 7 weeks. Primary endpoint was clinical and endoscopic remission at week 8. Secondary outcomes included clinical and endoscopic response, adverse events, and health-related quality of life using generic and disease-specific instruments. Results: From July 2017 to June 2021, 21 and 13 patients were randomized to FMT and placebo groups, respectively. The trial terminated early due to futility. At week 8, 0% (0/15) of patients in the FMT group versus 8.3% (1/11) in the placebo group reached the primary endpoint of combined clinical and endoscopic remission as per protocol analysis. There were no differences between the groups in clinical or endoscopic responses. One participant in each group had worsening of CD. Although both groups experienced statistically significant improvements in health-related quality of life, only the FMT group had a significant decrease in activity impairment. Although there were no significant changes in microbial diversity or composition, participants who achieved clinical response became more similar to their donors in stool microbial composition. Discussion: FMT was not effective at inducing clinical and endoscopic remission in CD using the FMT regimen in this study. Future studies may use other strategies to enhance treatment response, including longer intervention, antibiotic pretreatment, optimized donor-recipient pairing, and concomitant anti-inflammatory diet, biologic or small molecule therapies.

Intestinal ultrasound accurately predicts future therapy failure in Crohn's disease patients in a biologics-induced remission.

Intestinal ultrasound (IUS) is used to assess disease activity, complications, and treatment follow-up in Crohn's disease (CD). Less is known about the association of disease activity on IUS with the risk of future disease relapse during biologically sustained clinical remission in CD. The study aimed to investigate the association between IUS activity parameters and subsequent therapy failure in asymptomatic biologically treated patients with CD. A retrospective cohort study examined the association between IUS parameters and forthcoming therapy failure (drug discontinuation, dose escalation, corticosteroid use, hospitalization, or surgery) in CD patients on biological therapy in remission. A total of 57 patients with ileal (65%) or ileocolonic (35%) CD on biological therapy were included in the study. Therapy failure occurred in 50.8% [defined as need for dose escalation (31%), drug discontinuation (51.7%), steroid use (10.5%), and hospitalization (6.8%)] during a median follow-up of 5 (SD + 9.5) months after IUS. On univariate analysis, a bowel wall thickness (BWT) of 2.5 vs. 4 mm (P = 0.005), the existence of an enlarged lymph node (P = 0.02), and the loss of bowel wall stratification (P = 0.01) were correlated with therapy failure. On multivariable analysis, only BWT ≥ 4 mm was associated with the risk of future treatment failure (hazard ratio, 3.7; 95% confidence interval, 0.6-15; P = 0.02). Our findings suggest that BWT ≥4 mm during clinical remission is associated with subsequent treatment failure in patients with CD treated with biologics. Our results support the use of IUS for monitoring CD during remission and may point to a novel threshold for predicting disease reactivation.

Treat-to-Target in Inflammatory Bowel Disease: An Updated Survey of Treatment Strategies among Portuguese Gastroenterologists

Background: In 2018, the authors surveyed the clinical practices among Portuguese gastroenterologists (PGEs) regarding treatment targets in Crohn’s disease (CD) and ulcerative colitis (UC). Since then, new evidence has emerged supporting additional targets, such as transmural remission and histological remission. This study provides an updated assessment of treatment practices among PGE with special emphasis on these new targets. Methods: Using the Portuguese Inflammatory bowel disease Study Group (GEDII) physician database, we invited PGE to participate in an anonymous online survey. Results: Fifty-six physicians agreed to participate in the study. Deep remission, steroid-free clinical remission, endoscopic remission, and biomarker remission were ranked among the most important treatment targets in CD (89%, 80%, 89%, and 84%, respectively) and UC (82%, 84%, 79%, and 84%, respectively). In CD, transmural remission was considered a target by 70% of participants, with 48% agreeing to intensify treatment to achieve it. In UC, histological remission was aimed by only 45% of PGE with most (88%) being unwilling to intensify treatment to achieve this goal. Physicians were more likely to seek endoscopic remission in CD and UC in younger and healthier patients, compared to older patients with comorbidities. Conclusion: PGEs are increasingly pursuing tougher treatment targets such as transmural remission in CD and, to a lesser extent, histological remission in UC. Physicians are more willing to escalate treatment to achieve endoscopic remission in younger patients.

Successful treatment of Crohn's disease-related peripheral spondyloarthritis with upadacitinib: two case reports and case-based review.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease (CD), not only causes significant intestinal inflammation but also leads to extra-intestinal manifestations such as spondyloarthritis (SpA). Although the efficacy of tumor necrosis factor (TNF) inhibitors has been reported for IBD-related SpA, some cases still encounter treatment failure, highlighting the need for novel therapeutic alternatives. Recently, Janus kinase inhibitors have demonstrated their efficacy in IBD and SpA, yet their impact on CD-related SpA remains unexplored. Here we present the first two cases of CD-related peripheral SpA successfully treated with upadacitinib. Additionally, our literature review identified a reported case of CD-related peripheral SpA treated with tofacitinib. All cases achieved clinical remission of both CD and peripheral SpA with Janus kinase inhibitors, and no adverse events or disease relapses were reported during the observation period. Our cases and literature review highlight the promising potential of Janus kinase inhibitors as a novel treatment not only for intestinal inflammation of CD, but also for CD-related peripheral SpA.

Pro-motility Preparation Protocol May Reduce the Rates of Failed Patency Capsule Among Patients with Crohn's Disease in Clinical Remission.

Patency capsule (PC) ingestion is commonly used to minimize capsule retention in high-risk patients with Crohn's disease (CD). However, false-positive rates remain high, precluding the use of video capsule endoscopy (VCE). We aimed to compare the efficacy of two preparation protocols in reducing failed PC rates in patients with CD. This bi-center retrospective case-control study included adult patients with small-bowel CD in clinical remission who underwent PC ingestion. The pro-motility group followed a low-residue diet, then a clear fluid diet, and took bisacodyl after ingestion, while the control group followed only a clear fluid diet. The primary outcome was failed PC, defined as the absence of PC excretion or presence on abdominal X-ray at 30 h post-ingestion. Multivariable logistic regression was used to identify predictors of failed PC. Among 273 patients (83 in the pro-motility group, 190 controls), the pro-motility group was older (median 36 [27-48] vs. 31 [24-43], p = 0.012) and had a lower rate of B2/3 disease phenotype (32.5 vs. 53.1%, p = 0.002) compared to controls. The pro-motility group also had a lower failed PC rate (12.0 vs. 24.7%, p = 0.023). Longer disease duration (adjusted odds ratio (AOR) 1.053, 95% confidence interval (CI) 1.016-1.091, p = 0.005) increased the odds of failed PC, while the pro-motility protocol was protective (AOR 0.438, 95% CI 0.200-0.956, p = 0.038), outweighing the influence of B2/3 disease phenotype (AOR 1.743, 95% CI 0.912-3.332, p = 0.093). The pro-motility preparation protocol could substantially improve the success rates of the small-bowel patency test in patients with CD undergoing PC ingestion, potentially reducing the risk of capsule retention and associated complications.

Profiles and interactions of gut microbiome and intestinal microRNAs in pediatric Crohn's disease.

Since previous studies have focused on the change of the fecal gut microbiome and intestinal tissue miRNA in pediatric Crohn's disease (CD), the relationship between them in different stages is still not clear. This is the first study to explore the gut microbiota and miRNA and their correlations with the Pediatric Crohn's Disease Activity Index (PCDAI). Crohn's Disease Endoscopic Index of Severity (CDEIS), and calprotectin, by applying two omics approach in three different groups (active CD, CD in remission with exclusive enteral nutrition or infliximab induction therapy, and the healthy controls). Both gut microbiome structure and the miRNA profiles were significantly changed in the different stage of CD. Seven key gut microbiome at species and eight key miRNAs were found, and their close interactions were further fully investigated by miRNA target prediction.

Efficacy and safety of probiotics in IBD: An overview of systematic reviews and updated meta-analysis of randomized controlled trials.

Probiotics show promise in inflammatory bowel disease (IBD), yet knowledge gaps persist. We performed an overview of systematic reviews and an updated metanalysis of randomized controlled trials (RCT) assessing the effect of probiotics on Crohn's disease (CD) and ulcerative colitis (UC). MEDLINE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched up to September 2023. Primary outcomes were clinical remission and recurrence; secondary outcomes included endoscopic response and remission, and adverse events. We calculated odds ratios (OR) using a random-effects model in R. The quality of systematic reviews was assessed using the AMSTAR-2; the trials' risk of bias was evaluated using the Cochrane Collaboration tool. Evidence certainty was rated using the GRADE framework. Out of 2613 results, 67 studies (22 systematic reviews and 45 RCTs) met the eligibility criteria. In the updated meta-analysis, the OR for clinical remission in UC and CD was 2.00 (95% CI 1.28-3.11) and 1.61 (95% CI 0.21-12.50), respectively. The subgroup analysis suggested that combining 5-ASA and probiotics may be beneficial for inducing remission in mild-to-moderate UC (OR 2.35, 95% CI 1.29-4.28). Probiotics decreased the odds of recurrence in relapsing pouchitis (OR 0.03, 95% CI 0.00-0.25) and trended toward reducing clinical recurrence in inactive UC (OR 0.65, 95% CI 0.42-1.01). No protective effect against recurrence was identified for CD. Multi-strain formulations appear superior in achieving remission and preventing recurrence in UC. The use of probiotics was not associated with better endoscopic outcomes. Adverse events were similar to control. However, the overall certainty of evidence was low. Probiotics, particularly multi-strain formulations, appear efficacious for the induction of clinical remission and the prevention of relapse in UC patients as well as for relapsing pouchitis. Notwithstanding, no significant effect was identified for CD. The favorable safety profile of probiotics was also highlighted.

Infliximab serum concentrations in luminal Crohn's disease and its relationship with disease activity: A multicentric cross-sectional study

ObjectivesIn Latin America, experience with monitoring serum Infliximab (IFX) concentrations is scarce. Our study aimed to compare IFX serum concentrations between patients with active disease or in remission. Patients and methodsA cross-sectional study was performed in patients with luminal Crohn's disease (CD) during maintenance treatment with IFX. Patients were classified as in remission or disease activity according to clinical scores and endoscopic, radiological, and laboratory markers. A comparison of IFX trough levels between the two groups was performed. Results80 CD patients were included [41 (51%) in remission and 39 (49%) with active disease]. In the analysis of general disease activity, the median serum levels of IFX in patients with remission and with active CD were 5.63 [0.03–14.40] vs. 3.84 [0.03–14.40] (p=0.287). Furthermore, there was no difference in serum IFX concentrations in endoscopic, radiological, and laboratory activities. Only in the clinical evaluation there was a significant difference in the median serum IFX levels between patients in remission and disease activity, 5.63 [0.03–14.40] vs. 2.14 [0.32–10.54] (p=0.042). ConclusionsIFX serum concentrations during maintenance treatment were similar in patients with luminal CD in remission and general, endoscopic, radiological, and laboratory disease activity. Patients with clinically active disease had lower IFX concentrations than patients in remission.

Relationship between Ustekinumab trough concentrations and clinical, biochemical and endoscopic outcomes in Crohn's disease: A multi-center nationwide retrospective study (TARGET STUDY).

Ustekinumab has been shown to be effective in inducing and maintain clinical and endoscopic remission in Crohn disease (CD). We aim to assess whether ustekinumab trough levels are associated with improved outcomes in CD in real-life. We recruited patients with CD who were treated with ustekinumab for at least 6 months from January 2017 to June 2023. Patients received ustekinumab 6 mg/kg intravenous induction followed by 90 mg every 4-, 8-, or 12-weeks during maintenance were included. We assessed clinical, biochemical, and endoscopic outcomes. Trough concentrations of ustekinumab that were taken from week 42 to week 52 were measured. Primary outcome was to evaluate the relationship between ustekinumab trough concentrations and clinical remission, biochemical normalization, and endoscopic remission. Logistic regression was conducted to assess outcomes. A total of 137 patients with CD, median age of 32 years and 83 (60.6%) males. The median serum levels of ustekinumab measured was 7.2 mcg/mL (interquartile range [IQR] 3.1-9.6). Using Spearman correlation analysis, a strong negative correlation was observed between ustekinumab drug levels and simple endoscopic score (SES-CD) (r = -0.464, P < .001). Additionally, ustekinumab drug levels demonstrated substantial negative correlations with disease severity measured by Harvey-Bradshaw index (HBI) score (r = -0.582, P < .001), C-Reactive Protein (CRP) levels (r = -0.598, P < .001) and fecal calprotectin (FC) levels (r = -0.529, P < .001). A multivariable analysis adjusted for age, sex and body mass index (BMI) showed a significant association between ustekinumab serum drug levels and predefined outcomes. Ustekinumab serum drug level above 4.5 mcg/mL was associated with 24% increase in the likelihood of having an SES-CD score <3 (OR 1.24, confidence interval [CI] 1.12-1.37, P value < .001), 44% more likely to achieve HBI score <5 (OR 1.44, CI 1.26-1.65, P value < .001), 52% higher likelihood of CRP more than 10 (OR 1.52, CI 1.31-1.77, P < .001), and 42% increased likelihood of FC more than 250 (OR 1.42, CI 1.24-1.62, P < .001). Ustekinumab trough concentrations above 4.5 mcg/mL were associated with clinical, biochemical and endoscopic remission in CD. Prospective data is warranted to confirm these findings.

Factors Predicting Loss of Remission in Crohn's Disease Patients in Endoscopic Remission in the Real World: Results From TARGET-IBD.

There is limited evidence that histologic remission improves outcomes in Crohn's disease (CD). We aimed to characterize a cohort of patients with CD in endoscopic remission and explore factors associated with subsequent loss of remission (LOR). In total, 4474 patients were enrolled in TARGET-IBD, a longitudinal, observational cohort study. Patients with a normal steroid-free colonoscopy (index) were defined as "in endoscopic remission" and were followed for LOR, defined as presence of inflammation, erosion, ulceration, or stricturing on a subsequent colonoscopy or commencement of steroids. Histologic activity was dichotomized using standard of care reports for active inflammation. Unadjusted and multivariable-adjusted Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of LOR in relation to independent variables. Of 658 patients with CD with steroid-free endoscopic remission, the majority were female (57%), white (83%), non-Hispanic (93%); 20% had ileal and 20% isolated colonic disease. Inflammatory (B1) disease was the most common phenotype (43%). Of these 658 patients, 257 (39%) had histologic inflammation on index colonoscopy. Histologic inflammation at index colonoscopy was associated with nearly twice the LOR risk (HR 1.96, 95% CI: 1.50-2.57) with median time to relapse of 1.20 years. Biologic use at index was associated with lower LOR risk (monotherapy, HR 0.61, 95% CI: 0.45-0.82; combination therapy, HR 0.43, 95% CI: 0.28-0.66). Active histologic inflammation despite endoscopic remission, and lack of biologic use were independently associated with risk of subsequent LOR, providing evidence that histologic remission may impart improved outcomes in patients with CD.

Multi-Omics Characterization of Colon Mucosa and Submucosa/Wall from Crohn's Disease Patients.

Crohn's disease (CD) is a subtype of inflammatory bowel disease (IBD) characterized by transmural disease. The concept of transmural healing (TH) has been proposed as an indicator of deep clinical remission of CD and as a predictor of favorable treatment endpoints. Understanding the pathophysiology involved in transmural disease is critical to achieving these endpoints. However, most studies have focused on the intestinal mucosa, overlooking the contribution of the intestinal wall in Crohn's disease. Multi-omics approaches have provided new avenues for exploring the pathogenesis of Crohn's disease and identifying potential biomarkers. We aimed to use transcriptomic and proteomic technologies to compare immune and mesenchymal cell profiles and pathways in the mucosal and submucosa/wall compartments to better understand chronic refractory disease elements to achieve transmural healing. The results revealed similarities and differences in gene and protein expression profiles, metabolic mechanisms, and immune and non-immune pathways between these two compartments. Additionally, the identification of protein isoforms highlights the complex molecular mechanisms underlying this disease, such as decreased RTN4 isoforms (RTN4B2 and RTN4C) in the submucosa/wall, which may be related to the dysregulation of enteric neural processes. These findings have the potential to inform the development of novel therapeutic strategies to achieve TH.

Ustekinumab in pediatric patients with Crohn's disease: safety, and efficacy results from a multicenter retrospective study in China.

Ustekinumab (UST) is approved as an effective therapy for Crohn's disease (CD) in adults. Off-label use is increasing in the pediatric population, more data on safety and efficacy in pediatric patients with CD is urgently needed. This study aimed to evaluate the clinical efficacy and safety of UST in children and adolescents with Crohn's disease. This multicenter retrospective study carried out at three tertiary care centers, and identified children who received their first dose of UST at 18 years old or younger and followed up for a minimum of 24 weeks. Data on demographics, disease behavior, location and activity, treatment history were collected. The primary outcomes were clinical remission at weeks 24-32 and weeks 48-56 of UST therapy. Secondary outcomes were clinical response at the same time points, endoscopic remission, changes in C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin and fecal calprotectin, improvement in growth parameters, and rate of adverse events. Sixteen patients were included, and 11/13 (84.6%) continued to receive UST after 1 year. Our data demonstrate that the clinical remission rates were 41.7% at weeks 24∼32 with the Weighted pediatric CD activity index (wPCDAI) was lower than baseline (43.8, IQR: 31.3-51.9 vs.15, IQR: 5.6-25, p < 0.001) and 75% at weeks 48-56 with wPCDAI was lower than baseline (42.5, IQR: 23.8-50 vs. 7.5, IQR: 0-13.8, p = 0.004). Five of eleven children achieved endoscopic remission. No serious adverse events were recorded during the study period. UST is efficacious and safe in pediatric patients with CD. Pediatric patients could benefit from UST as either a primary or secondary biologic therapy for the induction, or maintenance of remission of CD.

Опыт применения устекинумаба у бионаивных пациентов с болезнью Крона, имеющих факторы неблагоприятного прогноза: реальная клиническая практика

The purpose of this study was to study the effectiveness of ustekinumab (UST) depending on the dosage regimen (90 mg subcutaneously once every 8 or 12 weeks) in patients with Crohn's disease (CD) who have unfavorable prognosis factors. Material and methods. To assess the effectiveness of the drug, we included in the study 38 patients with CD who had unfavorable prognosis factors, who were randomized into two groups of patients who received the drug in a 90 mg subcutaneous regimen once every 12 weeks (1-st group, n = 20) and 90 mg subcutaneously once every 8 weeks (2-nd group, n = 18). The gender and age of the patient were analyzed, including at the time of diagnosis, the severity and prevalence of CD; the presence of intestinal complications; the presence and localization of extra-intestinal manifestations; previous treatment was analyzed. Results. Clinical response and clinical remission were achieved in 19 (95.0%) patients of the first group and 18 (100.0%) patients of the second group (p &gt; 0.05). Clinical remission was maintained (without the need for optimization of therapy) by the 52 week of follow-up in 18 (90.0%) patients, in the second group – 18 (100.0%) patients (p = 0.516). In the 1-st group 10 (50.0%) patients achieved and maintained endoscopic remission by the 52 week of follow-up, in the 2-nd group – 16 (88.9%) patients (p = 0.01492). During one year of follow-up, 10 (50.0%) patients of the 1-st group maintained clinical and endoscopic remission of CD, 8 (40.0%) patients maintained clinical response and clinical remission (a decrease of ≥ 100 points from the initial CDAI), 16 (88.9%) patients in the 2-nd group maintained clinical and endoscopic remission of CD. Clinical response and clinical remission were maintained in 2 (11.1%) patients. Clinical and endoscopic remission in patients with CD receiving the drug was achieved in the 2-nd group (p = 0.01492). Without steroidal remission in patients in 1-st group was 65.0%, and in in 2-nd group about 95% (p = 0.04502). Conclusion. This clinical observation demonstrated statistically significantly higher therapeutic efficacy (clinico-endoscopic, without steroidal remission) in CD patients with adverse prognosis factors receiving UST 90 mg subcutaneously every 8 weeks.

Plasma bile acids in association with Crohn’s disease

Background In addition to facilitating lipid digestions, bile acids (BA) are signalling molecules acting on receptors on immune cells and along the gastrointestinal (GI) tract. The aim of this study was to assess if altered bile acid profiles in plasma are associated with Crohn’s disease (CD). Method This cross-sectional study included individuals (aged ≥18 years) referred for colonoscopy at a tertiary centre in Stockholm between 2016 and 2019. All participants received bowel preparation, completed a lifestyle questionnaire and provided blood samples for analysis. During colonoscopy, severity of disease was graded, and biopsies were taken from colonic mucosa. In the current substudy, 88 individuals with CD and 88 age-matched controls were selected for analysis of BA in plasma with ultra performance liquid chromatography (UPLC). Linear regression models were then used to compare mean bile acid concentrations and concentration ratios between CD and controls. Results Individuals with CD had lower plasma concentrations of the majority of secondary BA compared to controls, in total CD/CC ratio 0.60 (SE 0.12), p = 0.001. The most prominent observations were lower levels of deoxycolic acid derivates and lithocolic acid derivates among participants with CD. Moreover, plasma concentration for secondary BA among participants with active CD was significantly lower compared to those with CD in remission, CD active/CD remission ratio 0.65 (SE 0.11), p < 0.002. Conclusion Crohn’s disease may be associated with altered plasma bile acid composition. The significance of colonic bacterial diversity in this context needs to be investigated in further studies.

A potential brain functional biomarker distinguishing patients with Crohn's disease with different disease stages: a resting-state fMRI study.

The previous studies have demonstrated that patients with Crohn's disease in remission (CD-R) have abnormal alterations in brain function. However, whether brain function changes in patients with Crohn's disease in activity (CD-A) and the relationship with CD-R are still unclear. In this study, we aimed to investigate whether the different levels of disease activity may differentially affect the brain function and to find the brain functional biomarker distinguishing patients with different disease stages by measuring the amplitude of low frequency fluctuations (ALFF). 121 patients with CD and 91 healthy controls (HCs) were recruited. The clinical and psychological assessment of participants were collected. The criteria for the disease activity were the Crohn's disease activity index (CDAI) scores. CD-R refers to CD patients in remission which the CDAI score is less than 150. Conversely, CD-A refers to CD patients in activity which the CDAI score is ≥150. The ALFF was compared among three groups by performing one-way analysis of variance, followed by a post hoc two-sample t-test. Differences among the groups were selected as seeds for functional connectivity analyses. We also investigated the correlation among clinical, psychological scores and ALFF. Binary logistic regression analysis was used to examine the unique contribution of the ALFF characteristics of the disease stages. There were widespread differences of ALFF values among the 3 groups, which included left frontal pole (FP_L), right supramarginal gyrus (SG_R), left angular gyrus (AG_L), right cingulate gyrus (CG_R), right intracalcarine cortex (IC_R), right parahippocampal gyrus (PG_R), right lingual gyrus (LG_R), right precuneous cortex (PC_R), left occipital fusiform gyrus (OFG_L). Significant brain regions showing the functional connections (FC) increased in FP_L, SG_R, PC_R and OFG_L between CD-A and HCs. The erythrocyte sedimentation rate had a negative correlation with the ALFF values in PC_R in the patients with CD. The phobic anxiety values had a negative correlation with the ALFF values in OFG_L. The psychoticism values had a negative correlation with ALFF values in the IC_R. And the hostility values had a positive correlation with the ALFF values in CG_R. Significant brain regions showing the FC increased in FP_L, SG_R, CG_R, PG_R, LG_R and OFG_L between CD-R and HCs. In binary logistic regression models, the LG_R (beta = 5.138, p = 0.031), PC_R (beta = 1.876, p = 0.002) and OFG_L (beta = 3.937, p = 0.044) was disease stages predictors. The results indicated the significance of the altered brain activity in the different disease stages of CD. Therefore, these findings present a potential identify neuroimaging-based brain functional biomarker in CD. Additionally, the study provides a better understanding of the pathophysiology of CD.

In vitro mucin degradation and paracellular permeability by fecal water from Crohn's disease patients.

Aim: This study aimed to examine the impact of fecal water (FW) of active and remissive Crohn's disease (CD) patients on mucin degradation and epithelial barrier function. Methods: FW and bacterial membrane vesicles (MVs) were isolated from fresh fecal samples of six healthy controls (HCs) and 12CD patients. Bacterial composition was determined by 16S rRNA gene amplicon sequencing. Results: In vitro FW-induced mucin degradation was higher in CD samples versusHC (p<0.01), but not associated with specific bacterial genera. FW of three remissive samples decreased transepithelial electrical resistance in Caco-2 cells by 78-87% (p<0.001). MVs did not induce barrier alterations. Conclusion: The higher mucin-degradation capacity of CD-derived FW might suggest contributions of microbial products to CD pathophysiology.

The gut ileal mucosal virome is disturbed in patients with Crohn’s disease and exacerbates intestinal inflammation in mice

Gut bacteriome dysbiosis is known to be implicated in the pathogenesis of inflammatory bowel disease (IBD). Crohn’s disease (CD) is an IBD subtype with extensive mucosal inflammation, yet the mucosal virome, an empirical modulator of the bacteriome and mucosal immunity, remains largely unclear regarding its composition and role. Here, we exploited trans-cohort CD patients and healthy individuals to compositionally and functionally investigate the small bowel (terminal ileum) virome and bacteriome. The CD ileal virome was characterised by an under-representation of both lytic and temperate bacteriophages (especially those targeting bacterial pathogens), particularly in patients with flare-up. Meanwhile, the virome-bacteriome ecology in CD ileal mucosa was featured by a lack of Bifidobacterium- and Lachnospiraceae-led mutualistic interactions between bacteria and bacteriophages; surprisingly it was more pronounced in CD remission than flare-up, underlining the refractory and recurrent nature of mucosal inflammation in CD. Lastly, we substantiated that ileal virions from CD patients causally exacerbated intestinal inflammation in IBD mouse models, by reshaping a gut virome-bacteriome ecology preceding intestinal inflammation (microbial trigger) and augmenting microbial sensing/defence pathways in the intestine cells (host response). Altogether, our results highlight the significance of mucosal virome in CD pathogenesis and importance of mucosal virome restoration in CD therapeutics.

Structural brain morphometry differences and similarities between young patients with Crohn's disease in remission and healthy young and old controls.

Crohn's disease (CD), one of the main phenotypes of inflammatory bowel disease (IBD), can affect any part of the gastrointestinal tract. It can impact the function of gastrointestinal secretions, as well as increasing the intestinal permeability leading to an aberrant immunological response and subsequent intestinal inflammation. Studies have reported anatomical and functional brain changes in Crohn's Disease patients (CDs), possibly due to increased inflammatory markers and microglial cells that play key roles in communicating between the brain, gut, and systemic immune system. To date, no studies have demonstrated similarities between morphological brain changes seen in IBD and brain morphometry observed in older healthy controls.. For the present study, twelve young CDs in remission (M = 26.08 years, SD = 4.9 years, 7 male) were recruited from an IBD Clinic. Data from 12 young age-matched healthy controls (HCs) (24.5 years, SD = 3.6 years, 8 male) and 12 older HCs (59 years, SD = 8 years, 8 male), previously collected for a different study under a similar MR protocol, were analyzed as controls. T1 weighted images and structural image processing techniques were used to extract surface-based brain measures, to test our hypothesis that young CDs have different brain surface morphometry than their age-matched young HCs and furthermore, appear more similar to older HCs. The phonemic verbal fluency (VF) task (the Controlled Oral Word Association Test, COWAT) (Benton, 1976) was administered to test verbal cognitive ability and executive control. On the whole, CDs had more brain regions with differences in brain morphometry measures when compared to the young HCs as compared to the old HCs, suggesting that CD has an effect on the brain that makes it appear more similar to old HCs. Additionally, our study demonstrates this atypical brain morphometry is associated with function on a cognitive task. These results suggest that even younger CDs may be showing some evidence of structural brain changes that demonstrate increased resemblance to older HC brains rather than their similarly aged healthy counterparts.

P770 Proactive Infliximab monitoring improves the rates of transmural remission in Crohn’s disease – a propensity score matched analysis

Abstract Background Few patients can reach transmural remission in Crohn’s disease (CD) with currently available therapies. Proactive optimization of Infliximab (IFX) based on trough levels may potentially improve these results. Methods Retrospective cohort study including consecutive CD patients starting treatment with IFX. Rates of transmural remission were compared between patients with and without therapeutic drug monitoring (target level: 5-7 µg/mL). A propensity score matched analysis was performed to adjust for potential confounders (figure). Results 195 CD patients were included, 57.9% receiving proactive therapeutic drug monitoring. The rates of transmural remission were higher in patients under proactive therapeutic drug monitoring (37.2% vs 18.3%, P=0.004) with similar results in the propensity score matched analysis (34.2% vs 17.1%, P=0.025). In multivariate analysis, proactive therapeutic drug monitoring was independently associated with transmural remission: OR 2.95 95%CI(1.44-6.06), P=0.003. Conclusion Proactive optimization of IFX based on trough levels increases the rates of transmural remission in CD.

P359 Persistence of severe fatigue in adults with Crohn's disease in remission

Abstract Background Fatigue is a frequent manifestation in patients with Inflammatory Bowel Disease (IBD), including those in remission. The persistence of fatigue over time in inactive disease is not well known. We aimed to determine the prevalence and continuation of severe fatigue at baseline and at 12 months follow-up in a cohort of patients with Crohn’s disease (CD) in remission. Methods Adult patients with CD in remission, defined by age ≥18 years, HBI &amp;lt;5 and faecal calprotectin &amp;lt;250mcg/g, were recruited to the INTICO2 observational study. Baseline assessment included SF36, FACIT-F and IBD Control patient-reported outcome measures. After 12 months in routine care, participants were invited to repeat FACIT-F. Severe fatigue was defined as scoring FACIT-F &amp;lt;30. Baseline data was analysed for factors associated with the persistence of severe fatigue at 12 months. Results A total of 198 patients were studied at baseline, of which 141 completed both baseline and 12-month assessments. The correlation between FACIT-F scores at baseline and 12 months was r = 0.79 (p &amp;lt; 0.001). Twenty-five (17.7%) patients were severely fatigued at both baseline and 12-month follow-up, and 99 (72.1%) were not severely fatigued at either time. Of the 34 patients severely fatigued at baseline, 9 (26.5%) were not severely fatigued at 12 months. From the 107 patients who were not severely fatigued at baseline, 12 (7.5%) became severely fatigued at 12 months. Participants with ongoing severe fatigue at baseline and 12 months had significantly worse SF36 Mental Health scores, 64 v 80 (p &amp;lt;0.001), and more night waking due to IBD, 32.0% v 7.1% (p = 0.011), at baseline assessment than those not severely fatigued at either assessment, see Table 1. Eight patients had a clinical disease flare during the 12-month follow-up period. Conclusion Most patients in this cohort in remission continued to have similar fatigue severity at 12-month follow-up. A higher proportion of severely fatigued patients at baseline improved at 12 months than non-severely fatigued patients at baseline developing severe fatigue at 12 months. Factors at baseline associated with persistent severe fatigue were worse mental health and poor sleep secondary to IBD. These may represent areas where intervention could improve reported fatigue levels in remission.