Treatment Of Crohn's Disease Research Articles

Marginal zone lymphoma under anti-TNF treatment in Crohn disease

Marginal zone lymphoma under anti-TNF treatment in Crohn disease

Exclusive enteral nutrition remodels the intestinal flora in patients with active Crohn's disease

BackgroundAlthough there are many hypotheses, the pathogenesis of Crohn's disease (CD) is not completely clear so far. Exclusive enteral nutrition (EEN) is a routine measure in the treatment of active CD. We aimed at investigating the impact of EEN on patients with active CD from microbial metabolomics.Methods16S-rDNA sequencing technology and gas chromatography–mass spectrometer analysis were employed to investigate the modification of the intestinal flora and fecal short-chain fatty acid (SCFA) during the EEN.ResultsSeven patients with CD, who conducted EEN, were followed up successfully in the present study. The 8-week EEN resulted in a remission of the condition of subjects with active CD, as revealed by a significant decrease in erythrocyte sedimentation rate (ESR) (P = 0.018), C-reactive protein (CRP) (P = 0.028), and Crohn’s disease activity index (CDAI) (P = 0.018). The nutrition of the subjects was improved after an 8-week treatment course with EEN, which was associated with an increase in body mess index (BMI) (P = 0.018) and serum albumin (ALB) (P = 0.018) levels. Furthermore, our investigations revealed a significantly increased abundance of Firmicutes paralleled by decreased levels of Proteobacteria. With respect to the genus, five species of bacteria including Ruminococcus (P = 0.01), Lachnospiraceae (P = 0.02), Anaerotruncus (P = 0.04), Flavonifractor (P = 0.04), and Novosphingobium (P = 0.05) showed significantly increased abundance. This was accompanied by relative changes in fecal short-chain fatty acids levels. Moreover, we successfully constructed a stable model by combining these five significantly different genera to predict the therapeutic effect of EEN on patients with CD (AUC = 0.9598).ConclusionsThe findings indicated that EEN can alleviate the condition and the nutrition of patients with active CD by regulating the intestinal flora and influencing the expression level of fecal short-chain fatty acids.

Трудности дифференциальной диагностики воспалительных заболеваний кишечника

The clinical case of a complicated course of Crohn's disease (CD) in an elderly patient is presented. The article reflects thefeatures of the diagnosis, tactics of conservative and surgical treatment of CD. Timely diagnosis of colorectal cancer (CRC) in an elderly patient with CD also demonstrated.

Drug therapy and monitoring for inflammatory bowel disease: a multinational questionnaire investigation in Asia.

Background/Aims The incidence and prevalence of inflammatory bowel disease (IBD) is rising in Asia recently. The study aimed to obtain a comprehensive understanding of the current status of drug therapy and monitoring for IBD in Asia.Methods A questionnaire investigation on drug therapy and monitoring for IBD was conducted right before the 6th Annual Meeting of Asian Organization for Crohn’s & Colitis. Questionnaires were provided to Asian physicians to fill out via emails between March and May 2018.Results In total, responses of 166 physicians from 129 medical centers were included for analysis. Among the surveyed regions, the most average number of IBD specialist gastroenterologists and nurses was 4.8 per center in Taiwan and 2.5 per center in Mainland China, respectively. 5-Aminosalicylic acid/sulfasalazine (99.4%) was the most preferred first-line choice for mild-moderate ulcerative colitis (UC), meanwhile corticosteroid (83.7%) was widely applied for severe UC. The first-line medication for Crohn’s disease (CD) markedly varied as corticosteroid (68.1%) was the most favored in Mainland China, Japan, and South Korea, followed by infliximab (52.4%) and azathioprine (47.0%). Step-up strategy was preferred in mild-moderate UC (96.4%), while 51.8% of the physicians selected top-down treatment for CD. Only 25.9% and 17.5% of the physicians could test blood concentration of infliximab and antibody to infliximab in their hospitals, respectively.Conclusions The current status of drug therapy and monitoring for IBD in Asia possesses commonalities as well as differences. Asian recommendations, IBD specialist teams and practice of therapeutic drug monitoring are required to improve IBD management in Asia.

Differences in Clinical Presentation of Eosinophilic Esophagitis in Pediatric Patients With Ulcerative Colitis and Crohn Disease

Significance: Eosinophilic esophagitis (EoE) is an inflammatory condition characterized by T helper-2 (TH2) cytokines. Ulcerative colitis (UC) and Crohn disease (CD) are inflammatory conditions with different clinical presentations and immune profiles. UC is associated with TH2 cytokines and CD with TH1 cytokines. We investigated potential differences in the association of EoE with UC and CD because of these different immune profiles. Methods: We utilized ICD-9 and ICD-10 codes to find patients with inflammatory bowel disease (IBD) and EoE. We defined EoE as any esophageal biopsy with >15 eosinophils. We collected demographic, clinical, laboratory, endoscopic, and histological data. Results: Thirty patients had both EoE and IBD. 14.9% of UC patients had EoE and 5.7% of CD patients had EoE. 64.7% of UC patients presented with UC and EoE at the same time, whereas 76.9% of CD patients presented with EoE at follow up. Ten of 13 CD patients were on anti-tumor necrosis factor (TNF) at EoE diagnosis. No UC patients were on anti-TNF at EoE diagnosis. Eighty-three percent of CD patients had mild disease or were in remission, whereas 50% of UC patients had moderate to severe disease at the time of EoE diagnosis. Conclusion: A higher percentage of UC than CD patients had EoE. EoE was more likely to be present at the initial diagnosis of UC than CD. EoE was more likely after diagnosis and treatment of CD with anti-TNF, when CD activity was mild or in remission. The difference in presentation suggests that anti-TNF or it’s impact on inflammation may differentially impact the association of EoE with CD and UC.

Accuracy of Serum Leucine-Rich Alpha-2 Glycoprotein in Evaluating Endoscopic Disease Activity in Crohn's Disease.

Mucosal healing, confirmed by endoscopic evaluation, is the long-term goal of treatment for Crohn's disease (CD). Leucine-rich alpha-2 glycoprotein (LRG) is a new serum biomarker correlated with disease activity in inflammatory bowel disease. However, studies evaluating its relationship with CD, particularly in the context of small intestinal lesions, are scarce. The aim of this study was to investigate the accuracy of LRG in assessing endoscopic activity, especially remission, in patients with CD. Between July 2020 and March 2021, 72 patients with CD who underwent LRG testing and double-balloon endoscopy at the same time were included. Endoscopic activity was evaluated using the applied Simple Endoscopic Score for Crohn's disease, including small intestine lesions. The relationship of LRG with clinical symptoms and endoscopic activity was assessed, and its predictive accuracy was evaluated. Leucine-rich alpha-2 glycoprotein showed a significant positive correlation with endoscopic activity (r = 0.619, P < .001), even in patients with active lesions in the small intestine (r = 0.626, P < .001). Multivariate logistic regression revealed that LRG was the only factor associated with endoscopic remission. An LRG cutoff value of 8.9 μg/mL had a sensitivity of 93.3%; specificity of 83.3%; positive predictive value of 96.6%; negative predictive value of 71.4%; accuracy of 91.7%; and area under the curve of 0.904 for the prediction of endoscopic remission. Leucine-rich alpha-2 glycoprotein can be used in assessing endoscopic activity and is a reliable marker of endoscopic remission in CD patients. It can be an intermediate target in the treatment of CD.

IBD Subtype-Regulators IFNG and GBP5 Identified by Causal Inference Drive More Intense Innate Immunity and Inflammatory Responses in CD Than Those in UC.

Background: The pathological differences between Crohn’s disease (CD) and ulcerative colitis (UC) are substantial and unexplained yet. Here, we aimed to identify potential regulators that drive different pathogenesis of CD and UC by causal inference analysis of transcriptome data. Methods: Kruskal–Wallis and Dunnett’s tests were performed to identify differentially expressed genes (DEGs) among CD patients, UC patients, and controls. Subsequently, differentially expressed pathways (DEPs) between CD and UC were identified and used to construct the interaction network of DEPs. Causal inference was performed to identify IBD subtype-regulators. The expression of the subtype-regulators and their downstream genes was validated by qRT-PCR with an independent cohort. Results: Compared with the control group, we identified 1,352 and 2,081 DEGs in CD and UC groups, respectively. Multiple DEPs between CD and UC were closely related to inflammation-related pathways, such as NOD-like receptor signaling, IL-17 signaling, and chemokine signaling pathways. Based on the priori interaction network of DEPs, causal inference analysis identified IFNG and GBP5 as IBD subtype-regulators. The results with the discovery cohort showed that the expression level of IFNG, GBP5, and NLRP3 was significantly higher in the CD group than that in the UC group. The regulation relationships among IFNG, GBP5, and NLRP3 were confirmed with transcriptome data from an independent cohort and validated by qRT-PCR. Conclusion: Our study suggests that IFNG and GBP5 were IBD subtype-regulators that trigger more intense innate immunity and inflammatory responses in CD than those in UC. Our findings reveal pathomechanical differences between CD and UC that may contribute to personalized treatment for CD and UC.

Mucosal healing with methotrexate versus azathioprine treatment in pediatric Crohn's disease as reflected by fecal calprotectin.

The current treatment goal for inflammatory bowel disease (IBD) is achievement of mucosal healing (MH). While established with biologic or azathioprine (AZA) therapies, the data on MH with methotrexate (MTX( treatment is scarce. We aimed to compare MH rate as reflected by FC in children with Crohn's disease (CD) treated with either MTX or thiopurines monotherapy. A cross-sectional multicenter study including children with CD (<18 years), with documented mucosal ulcerations/erosions on their first endoscopy, who were in clinical and biochemical remission for at least 6 months on MTX or AZA/6-MP monotherapy and had fecal calprotectin (FC) measurements during remission. Clinical remission was defined as PCDAI<10 and normal C-reactive-protein (CRP) level. FC < 100 μg/gr was used as a marker of MH. Demographic, clinical and laboratory data were retrieved from the medical charts. 64 patients (41 males, age 16.6±4.2 years) were included; 36 with MTX, 26 with AZA and 2 with 6-MP treatment. The mean treatment dose was 14.0±1.8 mg/m2 for MTX, and 1.8±0.66 mg/kg for AZA, and mean therapy duration was 22 ±17.1 months. MH (FC < 100 μg/gr) was demonstrated in 14/36 (39%) and 18/28 (64%) of patients on MTX and AZA/6-MP therapy, respectively (p=0.04). Rates of FC < 300 μg/gr were comparable [27/36 (75%) MTX, 24/28 (86%) AZA/6-MP, p=0.29]. MH was associated with longer treatment duration (p=0.03). MH as reflected by FC < 100 μg/gr, was higher with AZA/6-MP compared to MTX treatment in pediatric CD.

Plasma miRNA Profile of Crohn's Disease and Rheumatoid Arthritis Patients.

Simple SummaryMicroRNAs are small, noncoding RNA, around 23 nt long molecules, expressed in different cell types and involved in post-transcriptional regulation. Importantly, these unique molecules can act directly in cells expressing them, but can also be secreted into blood affecting gene expression in distant or adjacent target cells, thus representing valuable circulating biomarkers of different diseases. In addition, miRNA gene target prediction indicates the important role in pathogenesis of a variety of autoimmune diseases, including Crohn’s disease (CD) and rheumatoid arthritis (RA). Our study of blood circulating miRNAs indicated that there are 99 differentially expressed miRNAs in CD patients and 57 in RA patients, when comparing with healthy individuals. This high number of differentially expressed miRNAs in both autoimmune diseases allowed us to select over 400 different biological processes that were similarly regulated between both groups of patients, which can pave the way to future mechanistic studies for better diagnosis or treatment for patients with Crohn’s disease and rheumatoid arthritis.Crohn’s disease (CD) and rheumatoid arthritis (RA) are immune mediated inflammatory diseases. Several studies indicate a role for microRNAs (miRNAs) in the pathogenesis of a variety of autoimmune diseases, including CD and RA. Our study’s goal was to investigate circulating miRNAs in CD and RA patients to identify potential new biomarkers for early detection and personalized therapeutic approaches for autoimmune diseases. For this study, subjects with CD (n = 7), RA (n = 8) and healthy controls (n = 7) were recruited, and plasma was collected for miRNA sequencing. Comparison of the expression patterns of miRNAs between CD and healthy patients identified 99 differentially expressed miRNAs. Out of these miRNAs, 4 were down regulated, while 95 were up regulated. Comparison of miRNAs between RA and healthy patients identified 57 differentially expressed miRNAs. Out of those, 12 were down regulated, while 45 were up regulated. For all the miRNAs down regulated in CD and RA patients, 420 GO terms for biological processes were similarly regulated between both groups. Therefore, the identification of new plasma miRNAs allows the emergence of new biomarkers that can assist in the diagnosis and treatment of CD and RA.

Emerging inflammatory bowel disease demographics, phenotype, and treatment in South Asia, South-East Asia, and Middle East: Preliminary findings from the Inflammatory Bowel Disease-Emerging Nations' Consortium.

Inflammatory bowel disease (IBD) is emerging in the newly industrialized countries of South Asia, South-East Asia, and the Middle East, yet epidemiological data are scarce. We performed a cross-sectional study of IBD demographics, disease phenotype, and treatment across 38 centers in 15 countries of South Asia, South-East Asia, and Middle East. Intergroup comparisons included gross national income (GNI) per capita. Among 10400 patients, ulcerative colitis (UC) was twice as common as Crohn's disease (CD), with a male predominance (UC 6678, CD 3495, IBD unclassified 227, and 58% male). Peak age of onset was in the third decade, with a low proportion of elderly-onset IBD (5% age>60). Familial IBD was rare (5%). The extent of UC was predominantly distal (proctitis/left sided 67%), with most being treated with mesalamine (94%), steroids (54%), or immunomodulators (31%). Ileocolic CD (43%) was the commonest, with low rates of perianal disease (8%) and only 6% smokers. Diagnostic delay for CD was common (median 12months; interquartile range 5-30). Treatment of CD included mesalamine, steroids, and immunomodulators (61%, 51%, and 56%, respectively), but a fifth received empirical antitubercular therapy. Treatment with biologics was uncommon (4% UC and 13% CD), which increased in countries with higher GNI per capita. Surgery rates were 0.1 (UC) and 2 (CD) per 100 patients per year. The IBD-ENC cohort provides insight into IBD in South-East Asia and the Middle East, but is not yet population based. UC is twice as common as CD, familial disease is uncommon, and rates of surgery are low. Biologic use correlates with per capita GNI.

Trocar Puncture With a Sump Drain for Crohn's Disease With Intra-Abdominal Abscess: A 10-Year Retrospective Cohort Study

BackgroundTraditional percutaneous catheter drainage (PCD) and surgical intervention could not always achieve satisfactory results for patients with Crohn's disease (CD) who have complications with intra-abdominal abscess. We proposed a trocar puncture with sump drainage for the treatment of CD with intra-abdominal abscess and compared it with the conventional PCD and surgical intervention.MethodsCrohn's disease patients with intra-abdominal abscess and admitted to our hospital from 2011 to 2020 were identified by reviewing the electronic medical records. We divided them into Trocar, PCD, and fecal diverting (FD) groups, according to the ways of treating an abscess. Outcomes, risk factors for abscess recurrence, and postoperative complications were compared among the three groups.ResultsA total of 69 patients were included and they were divided into Trocar (n = 18), PCD (n = 29), and FD (n = 22) groups. Four patients in the PCD group were transferred to receive the FD surgery due to the failure of initial treatment. The incidence of abscess recurrence was significantly higher in the PCD (48%) and FD (50%) groups compared to the patients using the trocar puncture with the sump drain (Trocar group) (16.7%). There were 8 patients in Trocar, 22 in PCD, and 20 s in the FD group who received enterectomy. None of the patients in the Trocar had an ultimate stoma and the incidence of postoperative complications was statistically lower [0% (Trocar) vs. 31.8% (PCD) vs. 45% (FD), P < 0.05]. The way of initial treating of the abscess was significantly correlated with the abscess recurrence and postoperative complications.ConclusionsTrocar puncture with a sump drain had a lower incidence of abscess recurrence, abdominal adhesions, postdrainage, and postoperative complications compared to the conventional PCD or surgical intervention.

Surgıcal Management of Crohn Dısease ın Chıldren: A Revıew Artıcle

Crohn’s disease (CD) is an inflammatory bowel disease with chronic transmural inflammation of the intestinal wall. It can be observed from oral cavity to anus and it typically involves the ileum, ileocecumor portions of the entire colon. With an increasing rate of CD in children, surgery still has a role in the management of this entity in children when medical treatment is unsuccessful. In this review article it is aimed to review the surgical treatment of CD under the light of relevant literature. During the management of children with CD, risks and benefits of surgical options should be carefully assessed and an appropriate surgical intervention should be performed promptly in order to avoid future complications and to gain future growth of the child with an acceptable quality of life.

Review article: emerging drug therapies in inflammatory bowel disease.

The landscape of inflammatory bowel disease (IBD) treatment is rapidly expanding with the development of new therapeutic options. To review the mechanisms of action and the available clinical trial data on emerging drug therapies for IBD. Pubmed, Medline and Cochrane databases were queried up to July 2021 using keywords "inflammatory bowel disease," "IBD," "Crohn's disease," "ulcerative colitis" and "trial," "phase" and "study." In addition, we manually reviewed the grey literature including clinical trial registries and abstracts from major gastroenterology conferences in 2020 and 2021 to include pertinent information. In ulcerative colitis (UC), phase 2b and/or phase 3 studies met primary endpoints for S1P receptor agonists (estrasimod, ozanimod), anti-IL-23 agent (mirikizumab), anti-lymphocyte trafficking agents (ontamalimab, subcutaneous vedolizumab), JAK inhibitors (upadacitinib, filgotinib) and TLR9 agonist (cobitolimod). In Crohn's disease (CD), anti-IL-23 agents (risankizumab, mirikizumab, guselkumab), JAK inhibitors (upadacitinib, filgotinib) and anti-lymphocyte trafficking agents (ontamalimab, etrolizumab) met primary endpoints in randomised controlled clinical trials. Several new IBD drug therapies have positive efficacy and safety data in early clinical trials, and there are several drugs in the therapeutic pipeline. As more treatments for CD and UC are approved for clinical use, research to assess predictors of response to therapy and head-to-head trials is needed to inform providers on how to best position therapeutic options for patients with IBD.

The Molecular Mechanisms of Intestinal Inflammation and Fibrosis in Crohn's Disease.

Crohn’s disease (CD) is an inflammatory bowel disease (IBD) with repeated remissions and relapses. As the disease progresses, fibrosis and narrowing of the intestine occur, leading to severe complications such as intestinal obstruction. Endoscopic balloon dilatation, surgical stricture plasty, and bowel resection have been performed to treat intestinal stenosis. The clinical issue is that some patients with CD have a recurrence of intestinal stenosis even after the medical treatments. On the other hand, there exist no established medical therapies to prevent stenosis. With the progressive intestinal inflammation, cytokines and growth factors, including transforming growth factor (TGF-β), stimulate intestinal myofibroblasts, contributing to fibrosis of the intestine, smooth muscle hypertrophy, and mesenteric fat hypertrophy. Therefore, chronically sustained inflammation has long been considered a cause of intestinal fibrosis and stenosis. Still, even after the advent of biologics and tighter control of inflammation, intestinal fibrosis’s surgical rate has not necessarily decreased. It is essential to elucidate the mechanisms involved in intestinal fibrosis in CD from a molecular biological level to overcome clinical issues. Recently, much attention has been paid to several key molecules of intestinal fibrosis: peroxisome proliferator-activating receptor gamma (PPARγ), toll-like receptor 4 (TLR4), adherent-invasive Escherichia coli (AIEC), Th17 immune response, and plasminogen activator inhibitor 1 (PAI-1). As a major problem in the treatment of CD, the pathophysiology of patients with CD is not the same and varies depending on each patient. It is necessary to integrate these key molecules for a better understanding of the mechanism of intestinal inflammation and fibrosis.

Influence of Corticosteroid Use on Short- and Long-Term Outcomes of Biologic Therapy for Inflammatory Bowel Diseases.

Corticosteroids (CS) are widely used to treat Crohn's disease (CD) and ulcerative colitis (UC), but are not recommended as maintenance therapy. Biologic drugs are widely used as an alternative to or in conjunction with CS to induce and maintain remission. This meta-analysis tested the hypothesis that CS use is associated with differential response to biologics. We identified published placebo-controlled clinical trials of biologic drugs approved for the treatment of CD or UC. Pooled estimates of the risk difference (RD) and 95% confidence intervals were derived from random effects models for induction of response and remission and maintenance of remission comparing biologic with CS versus biologic alone. Heterogeneity of response was estimated using I2. Fifteen studies met the inclusion criteria. Pooled estimates of the RD and I2 comparing biologic plus CS versus biologic alone were as follows: induction of UC response 0.15 (0.05, 0.25), I2 = 57.29% and CD response 0.02 (- 0.03, 0.06), I2 = 0.01%; induction of UC remission 0.03 (- 0.01, 0.08), I2 = 0.00% and CD remission 0.08(0.02, 0.14), I2 = 7.81%; and maintenance of UC remission - 0.06 (- 0.13, 0.01), I2 = 0.00% and CD remission - 0.06 (- 0.14, 0.03), I2 = 11.24%. Patients in the placebo arm of CD trials who were receiving CS were less likely to achieve remission during the induction phase (pooled RD - 0.05 (- 0.09, - 0.00), I2 = 0.00%). In this meta-analysis of placebo-controlled trials, CS use was associated with higher biologic response rates for UC and remission rates for CD during the induction phase, but were not associated with improved maintenance of remission.

Treatment patterns, persistence with therapy, and outcomes of ustekinumab in Crohn's disease: Real-world data analysis.

Background and AimIn 2017, ustekinumab (UST) was included in Israel's National Basket of Health Services for treatment of biologic‐experienced Crohn's disease (CD) patients with moderately to severely active disease. This study aims to provide real‐world evidence on persistence and clinical outcomes among early users of UST.MethodsThis retrospective cohort study was conducted using data from Maccabi Healthcare Services (MHS; 2.5‐million‐member state‐mandated health provider, Israel). Adult patients with a CD diagnosis code who had ≥1 dispensed UST prescription in 2017–2018 and at least 12 months of prior continuous health plan enrollment were included. Outcomes, including treatment discontinuation, dose‐escalation (based on shortened intervals between purchases), CD‐related surgery, CD‐related hospitalization, corticosteroid (CS) discontinuation, and use of opioids were evaluated from the date of first dispensed UST through the end of 2019 using Kaplan–Meier analysis.ResultsA total of 162 eligible patients (81 [49.4%] female; median age 34.4 years [IQR 23.2–46.3]; median years since CD diagnosis 8.6 [IQR 4·8–16.0]) were enrolled in the study. Discontinuation rate after 365 and 540 days of follow‐up was 27.8% and 35.6%. Dose escalation was estimated at 15.4% and 28.6%, respectively. The first‐year cumulative rate of CD‐related surgery and CD‐related hospitalization were estimated at 4.7% and 9.8%, respectively.ConclusionIn this real‐world CD cohort of UST users, results suggest persistence is relatively high as compared to other biologics for CD. Comparative effectiveness of different biologic treatments for CD in this population should be further explored.

ILEAL ENTEROCYTE BRUSH BORDER ABNORMALITIES ASSOCIATE WITH PROGRESSIVE DISEASE COURSE IN PEDIATRICS CROHN’S DISEASE

Abstract BACKGROUND Biomarkers are needed to identify the subset of Crohn’s disease (CD) patients at-risk for severe, treatment-refractory disease. Short ileal microvillus length (MVL) is an epithelial biomarker that predicted non-response to treatment in adult CD. Here, we hypothesized that short MVL phenotype would occur in pediatric CD and associate with more severe disease. METHODS H&amp;E-stained ileal tissue sections were obtained from 3 pediatric cohorts: WashU, CCHMC, and RISK (n=58 controls, n=377 CD). MVL was measured in regions not involved in acute inflammation. RISK had baseline “pre-treatment” and follow-up “post-treatment” sampling, clinical phenotyping, and transcriptomic data. Transmission electron microscopy (TEM) and immunofluorescence was performed on paired samples from 6 CD and 6 controls. RESULTS Ileal MVL was shorter in pediatric CD (mean: 1.44 μm) vs. controls (mean: 1.64 μm; P&amp;lt;0.0001). MVL did not associate with body mass index, disease location, endoscopic deep ulcers, or disease activity index scores. Histological inflammation scores were greater in baseline CD vs. controls, but similar between CD with short (defined as &amp;lt;1.46 μm, 10th percentile of controls) or normal MVL. Progression from B1 inflammatory disease behavior to B2 stricturing or B3 internal penetrating disease behavior was more likely to occur in patients with shorter MVL (n=91 follow-up samples collected prior to disease progression event; B2: P=0.0077, B3: P=0.0186). Additionally, progression to B2 occurred sooner in those with short follow-up MVL (P=0.0206). In contrast, associations with disease behavior progression based on baseline MVL were not observed. RNA-seq analysis identified 92 genes differentially expressed between CD and controls and correlated with MVL. Gene function analysis showed enrichment (P&amp;lt;0.001) for actin cytoskeleton, transporter activity, and plasma membrane among the 43 genes positively associated with MVL, and enrichment for myeloid cell, response to bacterium, and extracellular matrix among the 49 genes negatively associated with MVL. TEM showed thinning of the terminal web in CD, with diminished microvillus rootlet length and organelle-free zones, features associated with shortened or disorganized microvilli in mouse models. We next assessed terminal web-associated proteins, PLS1 and MYH14, and found that both were altered in CD samples; PLS1 was abnormally enhanced at the brush border, and MYH14 was aberrantly localized in the cytoplasm. Misexpression of MYH14 was associated with terminal web thinning and shorter MVL. CONCLUSIONS This study supports short ileal MVL phenotype in follow-up CD samples as an epithelial biomarker for more severe disease prognosis, particularly for progression to stricturing disease. Our data suggest that terminal web alterations underlie the short MVL phenotype.

P672 Biologic therapy for Inflammatory Bowel Disease in Poland in 2020: nationwide data

Abstract Background The number of patients in Poland diagnosed with ulcerative colitis (UC) or Crohn’s disease (CD) has been increasing in the last decade, which implies an increase in the number of severe cases, where biologic treatment is required. The aim of this study was to analyse the usage of biologic treatment among patients with both types of inflammatory bowel diseases (IBD) in Poland that was reimbursed by the National Health Fund (NFZ) in 2020. Methods The analysis was conducted using administrative data collected since the year 2009 by the National Health Fund (NFZ), the only public payer in Poland. We defined an IBD patient receiving biologic treatment as a patient: (1) who had at least two inpatient/outpatient records in the NFZ registry in the years 2009 – 2020 with ICD10 code K50/K51 assigned; (2) who had filled at least two prescriptions for IBD medications two months apart or who had undergone intestinal surgery prior to the record; (3) and who received biological treatment reimbursed by the NFZ in 2020. We assessed the total percentage of patients with each diagnosis who received biologic treatment as well as the percentage by sex, by age group and by the place of residence (voivodeship). Results In 2020, the percentage of patients treated with biologic agents in the population of CD patients was 7.9% (1 863 / 23 574). The percentage of patients treated with biologic agents in the population of UC patients was 1.6% (1 174/73 235). The rate of patients treated with biologics for both CD and UC was significantly lower in women than in men (p&amp;lt;0,001 for both). Among all age groups, the highest percentage of patients receiving biologic treatment for both CD and UC (21,7% and 6,5%, respectively) was observed in those aged 10–19 years and the lowest percentage in patients aged over 70 years (0,8% for CD, 0,2% for UC). The highest proportion of patients treated with biologic drugs among CD patients was found in the Mazovian Voivodeship (13.8%) and the lowest - in the Lubusz Voivodeship (1.2%). In UC, the highest biologic treatment rate was observed in the Świętokrzyskie Voivodeship (3.1%), and the lowest in the Lubusz Voivodeship and the Warmian-Masurian Voivodeship (both 0.2%). Conclusion The use of biologic agents in the treatment of both Crohn’s disease and ulcerative colitis in Poland has been presented. Female patients receive biologic treatment for IBD significantly less frequently than male. The highest proportion of patients receiving biologic treatment for both CD and UC was found in the paediatric population. There are voivodeships in Poland where the access to biological treatment is unacceptably low.

DOP82 Achievement of steroid-free remission in patients with moderately to severely active Crohn’s Disease during treatment with risankizumab

Abstract Background The efficacy and safety of risankizumab (RZB) as induction and maintenance therapy for patients with moderately to severely active Crohn’s disease (CD) has been documented. Steroid-free clinical remission is an important additional treatment goal in CD. The efficacy of RZB by baseline steroid use during induction and steroid-free outcomes during maintenance was examined. Methods In ADVANCE (NCT03105128) and MOTIVATE (NCT03104413), patients with moderately to severely active CD received intravenous (IV) RZB induction therapy or placebo (PBO) for 12 weeks. Patients with clinical response to RZB were re-randomised in a 52-week maintenance study (FORTIFY; NCT03105102) to subcutaneous (SC) RZB or PBO (ie, withdrawal). Patients receiving steroids (maximum prednisone or equivalent ≤ 20 mg/day; budesonide ≤ 9 mg/day) at baseline of the induction studies maintained stable doses for the 12-week study duration. A mandatory steroid taper per protocol was initiated at the beginning of maintenance for patients receiving steroids during induction. Patients losing clinical response (per investigator assessment) after initiation of taper could have their steroid dose increased up to the induction baseline dose. This analysis included patients who received RZB 600 mg IV in ADVANCE or MOTIVATE and patients who received RZB 360 mg SC in FORTIFY. Endpoints reported included clinical remission (defined by CD Activity Index [CDAI] or stool frequency/abdominal pain score [SF/APS] criteria) at week 12 of induction by baseline steroid use, steroid-free clinical remission (CDAI or SF/APS), steroid-free endoscopic response, and steroid-free endoscopic remission at week 52 of maintenance. Steroid discontinuation rates over 52 weeks of maintenance were also assessed. Results Induction of clinical remission at week 12 with RZB 600 mg IV in ADVANCE or MOTIVATE was independent from baseline steroid use (Figure 1).Clinical remission rates (CDAI or SF/APS) at week 12 were similar for patients using steroids vs those who were not (33.8%–42.0% vs 34.9%–46.6%; Figure 1). Steroid use decreased over time in FORTIFY, with a greater proportion of patients receiving RZB 360 mg SC discontinuing steroids at week 52 vs withdrawal (PBO SC; Figure 2A). Rates of steroid-free clinical remission (P ≤ .012), steroid-free endoscopic response (P &amp;lt; .001), and steroid-free endoscopic remission (P &amp;lt; .001) were significantly higher with RZB 360 mg SC vs withdrawal (PBO SC) at week 52 of maintenance (Figure 2B–2C). Conclusion Efficacy of RZB induction therapy was independent of baseline steroid use. RZB maintenance promotes high rates of steroid-free clinical and endoscopic outcomes, demonstrating a benefit of RZB treatment in CD.

P385 Tailoring induction treatment for children with Crohn’s disease

Abstract Background Multiple clinical studies in children with Crohn’s disease (CD) have demonstrated the high efficacy of nutritional therapy with exclusive enteral nutrition (EEN) to induce remission and even to promote mucosal healing. However, EEN as inductive treatment may be not tolerated or inefficient and we are well aware of the paramount importance of a well conducted induction treatment for paediatric CD with the goal of an individualized induction treatment to improve the prognosis and the quality of life of inflammatory bowel disease (IBD) children. Methods A retrospective multicentre study including newly diagnosed children with CD treated with EEN as induction therapy was designed. The primary aim of the study was to study predictive factors of non- adherence to treatment. The secondary endpoint were predictive factors of clinical non-remission at the end of induction treatment. Those data together were analysed with the ultimate goal of trying to define an individualized induction treatment for children with CD. Results 376 CD children from, 14 IBD paediatric referral centres were enrolled in the study. The rate of EEN adherence was, 89 %. Colonic involvement and FC &amp;gt;, 600 μg/g at diagnosis were found associated with a reduced EEN adherence in univariate and multivariate analysis. The remission rate of those who completed induction treatment was, 67%. A multivariate analysis showed that factor determining lower remission rate were age &amp;gt;, 15 years and PCDAI &amp;gt;, 50. With those results we were able to create a decisional algorithm which is provided in figure 1. Conclusion EEN administered for, 8 weeks is effective for inducing clinical remission. The rate of adherence is high but there is a group of patients (colonic involvement + hight FC) which are at risk of non-adherence and thus may be candidate for alternative dietary induction regimens. Moreover, older patients with moderate to severe active disease (PCDAI&amp;gt;40), are at higher risk of failing clinical remission achievement after EEN and may benefit from an early anti-TNF alpha treatment. Personalized treatment strategies should be proposed weighing the benefits and risks based on each patient’s disease location, phenotype and disease activity with the overall aim of obtaining rapid control of inflammation to reduce long-term bowel damage.