Journal of Crohn's and Colitis最新文献

{"title":"P525 Utilisation of endoscopic ultrasonography for submucosal cushion measurement to determine eligibility for endoscopic submucosal dissection in ulcerative colitis-associated dysplasia: A case series","authors":"K Kim, S W Hong, S W Hwang, S H Park, B D Ye, J S Byeon, S J Myung, S K Yang, D H Yang","doi":"10.1093/ecco-jcc/jjad212.0655","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0655","url":null,"abstract":"Background Endoscopic submucosal dissection (ESD) has gained traction as an effective therapy for ulcerative colitis (UC)-associated dysplasia, yet identifying fitting ESD candidates is challenging by substantial submucosal (SM) fibrosis from chronic inflammation. We report our experience utilising endoscopic ultrasonography (EUS) to assess ESD eligibility by measuring SM cushion thickness. Methods Retrospective case-series includes nine patients who were diagnosed or referred to as UC-associated dysplasia in surveillance colonoscopies between August 2017 and October 2023. After scanning dysplastic lesions (Fig A-B), hyaluronic acid solution was injected into the SM layer (Fig C). EUS with a mini-probe quantified SM cushion beneath the dysplastic lesion (Fig D), and ESD was performed in cases with at least 2.0 mm of SM cushion thickness (Fig E-F). Results Among ten cases from nine patients, eight cases met the criteria and underwent ESD, while two cases (Patient 3, Patient 7) were regarded as unsuitable for ESD with SM cushion thickness less than 2.0 mm. Median disease duration was 19 years, and median age at diagnosis of UC-associated dysplasia was 50 years. Median SM cushion thickness ranged from 4.2 to 6.9 mm. Median procedure time was 50 minutes, and median size of resected specimens and lesions were 31.5 x 24.5 mm and 16.0 x 12.5 mm, respectively. en bloc resection was achieved in all cases, with an 87.5% R0 resection rate. No perforation occurred; only one required post-discharge endoscopic bleeding control after four days post-discharge. Conclusion EUS-measured SM cushion thickness may be a valid approach that provides an objective criterion for determining ESD eligibility in UC-associated dysplasia. This would help guide individualised treatment in UC-associated dysplasia, reducing unnecessary procedures or surgery.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P661 Ustekinumab in Crohn’s disease: A three-year multicentre prospective study from Hungary - Assessing efficacy, drug sustainability, and safety","authors":"L J Barkai, L Gonczi, K Farkas, B Farkas, T Molnar, T Szamosi, E Schafer, P Golovics, M Juhasz, A Patai, A Vincze, P Sarlos, A Farkas, Z Dubravcsik, T G Toth, P Miheller, P L Lakatos, A Ilias","doi":"10.1093/ecco-jcc/jjad212.0791","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0791","url":null,"abstract":"Background While randomized controlled trials have shown ustekinumab (UST) as an effective therapeutic option for Crohn’s disease (CD), there is a lack of long-term observational data in real-world CD patient settings. This prospective study seeks to evaluate the clinical effectiveness, sustainability, and safety of UST in a nationwide multicentre cohort of CD patients over three years. The aim is to bridge the gap in our understanding of UST's real-world implications for long-term CD management. Methods CD patients undergoing ustekinumab (UST) treatment were consecutively enrolled at nine Hungarian Inflammatory Bowel Disease centers from January 2019 to May 2020. Over a three-year period, comprehensive data on patient demographics, disease characteristics, treatment history, clinical disease activity (measured by the Harvey Bradshaw Index (HBI)), biomarkers, and endoscopic activity (evaluated using the Simple Endoscopic Score for Crohn’s Disease (SES-CD)) were systematically collected. Results Involving 148 patients, the cohort comprised 48.9% with complex behavior of CD and 97.2% with previous anti-TNF exposure. Pre-induction remission rates were observed at 12.2% (HBI) and 5.1% (SES-CD). Clinical remission rates (HBI) at the end of the first, second, and third years were 52.2%, 55.6%, and 50.9%, respectively. Criteria for endoscopic remission were met in 14.3%, 27.5%, and 35.3% of subjects at the end of the first, second, and third years. Dose intensification was notable, with 84.0% of patients on an 8-weekly and 29.9% on a 4-weekly regimen by the end of year 3. Throughout the follow-up period, drug sustainability stood at 76.9%, and no serious adverse events were observed. Conclusion Our study confirms that ustekinumab is a sustainable, effective, and safe long-term treatment for Crohn's disease patients with a severe disease phenotype and a history of high anti-TNF failure, with the need for frequent dose adjustments.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P958 Comparison of Paediatric Patients and Young Adults with Moderately to Severely Active Crohn’s Disease Treated with Ustekinumab in the REALITI Real-World Evidence Effectiveness Study","authors":"S Steiner, S Shehzad, J Adler, R B Colletti, R Strauss, J Heile, O Adedokun, A Sheahan, R Zhang, K H Lo, L Kim, Y Xiao, S Volger","doi":"10.1093/ecco-jcc/jjad212.1088","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.1088","url":null,"abstract":"Background Few approved treatment options exist for paediatric patients (pts) with Crohn’s disease (CD). Paediatric inflammatory bowel disease (IBD) medication approvals are delayed nearly 7 years after adult approvals,1 resulting in off-label use and potential for incorrect dosing. The REALITI Study evaluated the effectiveness and safety of ustekinumab (UST) in routine clinical care in paediatric pts (age 2-<18) and young adults (age 18-25) with moderately to severely active CD (Short Paediatric CD activity [sPCDAI] score ≥30) using data from the ImproveCareNow (ICN) Registry. Methods Effectiveness data from pts with CD treated with UST were extracted from the ICN Registry between 10 January 2010 and 29 February 2020. A supplemental, retrospective chart review was conducted to collect data not in the ICN Registry. The primary endpoint was clinical remission (sPCDAI≤10) at Week (Wk) 52. All data were summarized descriptively, and the proportion of pts achieving clinical remission and associated 2-sided 95% confidence interval were calculated across multiple populations. Rates of discontinuations, IBD-related hospitalizations, surgeries, and serious infections were also calculated. Results A total of 479 CD pts in ICN were treated with UST, including 348 paediatric pts and 131 young adults. We report an analysis of 114 paediatric pts who weighed >40 kg and had a sPCDAI ≥30. All pts were treatment refractory; 99.1% had not responded to prior biologic therapies, with less than 1% biologic naïve. Results were compared to 51 ICN young adults with moderately to severely active CD, a population for which UST is approved. Clinical remission at Wk 52 was achieved in 22.8% (26/114; 95% CI: 16.1%, 31.3%) of paediatric pts vs 21.6% (11/51; 95% CI:12.5%, 34.6%) of young adults (Figure 1A). Discontinuation rates through Wk 52 were similar between paediatric pts (25.4%) and young adults (25.5%; Figure 1B). Overall, 36.0% of paediatric pts and 21.6% of young adults had IBD-related hospitalizations. IBD-related surgery was reported in 14.0% of paediatric pts and 11.8% of young adults. Serious infections occurred in 9.6% of paediatric pts and 3.9% of young adults. Opportunistic infections occurred in 1.8% of paediatric pts and 0% of young adults. No events of tuberculosis, malignancy, or anaphylaxis requiring UST discontinuation occurred in either group. No deaths were reported. Conclusion This study of real-world data from the ICN Registry found similar remissions rates in paediatric pts and young adults with CD treated with UST, suggesting comparable effectiveness of UST in both age groups. No new safety signals were identified. (Crowley E, et al. J Crohns Colitis. 2022 Feb 23;16(2):331-335.)","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P335 Development and validation of a Belgian set of quality indicators for inflammatory bowel diseases","authors":"L Fierens, C Liefferinckx, J Sabino, E de Dycker, V Wambacq, K Vanhaecht, F Rademakers, P Bossuyt, F Baert, D Baert, M Ferrante","doi":"10.1093/ecco-jcc/jjad212.0465","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0465","url":null,"abstract":"Background Quality indicators are standardized, evidence-based measures of health care quality, categorised as structure (to assess the care setting), process (to assess high-quality care actions by healthcare professionals) or outcome indicators (results of actions undertaken by healthcare professionals). Several quality indicator sets have been developed to standardise, measure and optimise IBD care. Our aim was to develop and validate a set to assess IBD care in Belgium and to select a subset of indicators with room for improvement that can be used to implement and improve care in clinical practice. Methods The importance of 221 quality indicators (49 structure, 135 process and 37 outcome) identified through literature was scored on a 10-point Likert scale in a two-round modified Delphi exercise by IBD experts. In a third round, the experts indicated and ranked their top 10 indicators with most room for improvement benefitting the patient in the Belgian healthcare system to agree on an improvement subset. In parallel, patient perspectives were collected through two linguistic patient focus groups, one in Flemish (6 participants) and one in French (4 participants). A final consensus meeting was organised to discuss 1) the patient perspectives gained through the focus groups, 2) the results of two Delphi scoring rounds and 3) the results of the additional ranking round. Indicators scoring ≥7 by ≥80% of the participants during the second scoring round, or based on agreement during the consensus meeting, were included in the final set. Results Thirty-two experts (11 IBD nurses and 21 clinicians including 2 paediatricians) participated in all three voting rounds, of which 19 also participated in the consensus meeting (6 IBD nurses and 13 IBD clinicians including 2 IBD paediatricians). In total, 199 quality indicators were agreed upon to assess IBD care in Belgium (41 structure, 123 process and 35 outcome). Eighteen (3 structure, 14 process and 1 outcome; Table) were retained in the improvement subset, related to patient characteristics, endoscopy guidelines, infection prevention, steroid use, the IBD care team, services provided in the IBD clinic, the documentation of patient characteristics, the care pathway and the monitoring of disease activity. The decision to include the latter five themes was driven by the importance to patients, which was evident from the patient focus groups. Conclusion An evidence and consensus based set of quality indicators was developed and validated - including an improvement subset - allowing Belgian IBD centres to evaluate quality of provided care, set up quality improvement projects and potentially launch a benchmarking study.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P374 Real-life effectiveness and safety of ustekinumab treatment in patients with ulcerative colitis: An Asan-Crohn’s and Colitis Association in Daegu-Gyeongbuk (CCAiD) multicenter cohort study","authors":"J E Baek, E S Kim, K O Kim, H H Jo, S W Hwang, S H Park, B I Jang, E Y Kim, S K Yang, S K Kim, B D Ye","doi":"10.1093/ecco-jcc/jjad212.0504","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0504","url":null,"abstract":"Background The real-life data on ustekinumab (UST) for Asian patients with ulcerative colitis (UC) are limited. We aimed to assess effectiveness and safety of UST for Korean patients with UC. Methods This was a multicenter retrospective study on patients with UC who received UST at 4 academic centers in Korea between January 2021 and April 2023. The primary endpoint was clinical remission defined as partial Mayo score (PMS) ≤2 and no subscore >1 at week (W) 8 of therapy. Secondary endpoints included clinical remission (W16–20 and W52–56), corticosteroid-free clinical remission (W8, W16–20 and W52–56), clinical response defined as reduction of PMS ≥3 and at least 30% from baseline with either a decrease in rectal bleeding subscore ≥1 or an absolute rectal bleeding subscore ≤1 (W8, W16–20 and W52–56), endoscopic remission defined as Mayo endoscopic subscore 0–1 (W16–20 and W52–56), durability of UST at W52–56 and adverse events. Results A total of 55 patients were included and 54 were analyzed excluding one in clinical remission at baseline (Male, 66.7%; Median age at UST initiation, 44.5 years; Disease duration at UST initiation, 7.5 years; Previous exposure to biologics/small molecules, 70.4%; Extensive colitis, 64.8%; Median baseline Mayo score, 8; Concomitant use of systemic corticosteroids, 48.1%; Concomitant use of immunomodulators, 38.9%). Out of 54 patients, 27 patients (50%) reached to W52–56 or stopped UST, while remained 27 patients still under maintenance UST therapy, not reaching W52–56. At W8, W16–20, and W52–56, 53.7% (29/54), 63% (34/54), and 44.4% (12/27) achieved clinical remission and 68.5% (37/54), 70.4% (38/54), and 51.9% (14/27) showed clinical response, respectively (Figure 1). Endoscopic remission rates at W16–20 and W52–56 were 57.4% (31/54) and 37% (10/27), respectively (Figure 1). The durability of UST at W52–56 was 74.1% (20/27). Multivariable analysis revealed that previous exposure to biologics/small molecules was negatively associated with clinical remission at W8 (OR: 0.10; 95% confidence interval [CI] 0.02–0.57; p=0.01) and W16–20 (OR: 0.18; 95% CI 0.04–0.91; p=0.04), whereas the concomitant use of immunomodulators showed a positive association with clinical remission at W8 (OR: 4.19; 95% CI 1.11–15.77; p=0.03). Adverse events occurred in 23 patients (42.6%) and serious adverse event in one patient (1.9%) (Table 1). Conclusion UST was effective with an acceptable safety profile for Korean patients with UC. Previous exposure to biologics/small molecules was negatively associated with clinical remission at both W8 and W16–20. Financial Support This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT) (NRF-2021R1A2C2095096).","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P698 Effectiveness and Safety of Ustekinumab for Ulcerative Colitis: A Brazilian Multicentre Real-World Observational Study","authors":"R Parra, J M F Chebli, M Freitas Cardoso de Azevedo, L A Chebli, G P Zabot, O S Cassol, R D S B Fróes, G O Santana, M Lubini, D O Magro, M Imbrizi, A C S Moraes, F V Teixeira, A J T Alves Jr, N L T Gasparetti Junior, S D C Ferreira, N S F Queiroz, P G Kotze, O Féres","doi":"10.1093/ecco-jcc/jjad212.0828","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0828","url":null,"abstract":"Background Real-world data on the effectiveness and safety of ustekinumab (UST) in ulcerative colitis (UC) are lacking in Latin America. In this study, we aimed to describe the effectiveness and safety of UST in a real-world multicentre cohort of Brazilian patients with UC. Methods We conducted a multicentre retrospective observational cohort study, including patients with moderate to severe UC (Total Mayo score 6-12, with an endoscopic subscore of 2 or 3) who received UST. The co-primary endpoints were clinical remission, defined as a total Mayo score ≤2 at 1 year, with a combined rectal bleeding and stool frequency subscore of ≤1, and endoscopic remission (endoscopic Mayo subscore of zero) within one year from baseline. Secondary endpoints included clinical response between weeks 12-16, endoscopic response within one year of starting UST, steroid-free clinical remission at week 52, and biochemical remission at week 52. We also evaluated UST treatment persistence and safety. Results A total of 50 patients were included (female, n=36, 72.0%), with a median disease duration of 9.2 years (1-27). Most patients had extensive colitis (n=38, 76.0%), and 43 (86.0%) were steroid-dependent at baseline. Forty patients (80.0%) were previously exposed to biologics (anti-TNF drugs, n=31; vedolizumab [VDZ], n=27). The co-primary endpoints of clinical remission and endoscopic remission at 1 year were achieved by 50.0% and 36.0% of patients, respectively. Clinical response at weeks 12-16 was 56.0%, endoscopic response, steroid-free clinical remission, and biochemical remission at week 52 were 68.0%, 67.4%, and 50.0%, respectively. The UST treatment persistence rates at 24 months was 73.7%. During the follow-up, 10 patients (20.0%) were hospitalized, mostly due to disease progression, and three patients required colectomy. Nine patients (18.0%) discontinued the drug mainly due to a lack of effectiveness. Twenty-six adverse events (AEs) were reported, 15 of which were considered as serious AEs. Conclusion This is the first real-world experience study to report the effectiveness and safety of UST specifically in a Latin American population. In this real-world cohort of difficult-to-treat UC patients, UST was associated with improvements in clinical, biochemical, and endoscopic outcomes. The safety profile was favorable, consistent with the known profile of UST.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DOP73 Early biological use in a Belgian, prospective inception cohort of patients with Inflammatory Bowel Disease: the PANTHER cohort","authors":"S Verstockt, E Glorieus, M De Wolf, M Lenfant, M Barbaraci, J Sabino, M Ferrante, J Geldof, B Verstockt, D Laukens, I Cleynen, L Vandermeulen, T Lobaton, S Vermeire","doi":"10.1093/ecco-jcc/jjad212.0113","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0113","url":null,"abstract":"Background The growing number of advanced therapies has revolutionized the management of inflammatory bowel disease (IBD). Although early use of biological therapies is associated with better long-term outcomes, no data exist for the Belgian population. To this end, we evaluated treatment patterns in biological use and persistence in a Belgian inception cohort. Methods The PANTHER (Prognostic biobANk of paTients witH Early cRohn’s or colitis) cohort consists of adult IBD patients recruited in 3 Belgian IBD referral centres. Patients are included within 3 months after diagnosis and are naïve for immunosuppressives and biologicals, and without previous IBD-related surgery. Treatment use and outcomes are prospectively collected, and time trends for biological use were analysed using log-rank tests and Cox regression (R 4.3.2). Results Between 2015 and 2023, a total of 473 newly-diagnosed IBD patients were recruited (270 Crohn’s disease (CD) [57%]; 199 ulcerative colitis (UC) [42%]; 4 [1%] IBD type unclassified) (Table 1). During a median (IQR) follow-up of 2.6 (1.3-4.3) years, 64 patients (14%) required surgery (n=10 colectomy; n=54 ileocecal/small bowel resection); and 250 patients (53%) received biological therapy within the 1st year after diagnosis. Most patients were treated with anti-TNF (CD 67%; UC 55%) as first-line biological, followed by anti-integrins (CD 24%; UC 43%) and anti-IL12/23 (CD 9%; UC 2%). Time series analysis showed a significant increase in biological use within the 1st year after diagnosis when comparing patients diagnosed between 2015-2017 (44%) to those between 2018-2020 (57%), and to 2021-2023 (66%) (p=0.03) (Fig. 1A). Factors associated to this early biological use were younger age (HR=0.99 [95%CI: 0.98-0.99]), a diagnosis of CD (HR=2.2 [95%CI: 1.6-2.8]); and perianal disease in CD (HR=2.8 [95%CI: 1.8-12.8]). Within this early biological exposure group, 26 patients (10%) needed a resection later on. Therapy persistence over time was higher with early exposure rates in patients diagnosed in 2021-2023 (82%) and 2018-2021 (71%), as compared to 2015-2017 (63%) (p=0.08) (Fig.1B). The mode-of-action of first-line biological did not show any association with persistence (HR=1.0 [95%CI: 0.4-3.0]). Overall, only 26% of patients had to switch to a second-line, with a switch [anti-TNF >anti-IL12/23] being the most frequent in CD (50%); and from [anti-TNF >anti-integrins] (46%) or vice versa (40%) in UC. Conclusion In this Belgian inception cohort, two thirds of patients are currently initiated with biological therapy within the first year after diagnosis. This increased biological use is associated with high therapy persistence rates of >80% after a median follow-up of 1.5 years, and with low rates of surgical resections.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P354 Tryptophan metabolites as predictive biomarkers for dietary therapy outcomes in paediatric Crohn's disease","authors":"M Ghiboub, N van der Kruk, R Sigall Boneh, E Wine, C M Verburgt, T G J de Meij, M Löwenberg, K B Gecse, J P M Derikx, W J de Jonge, G D’Haens, J E Van Limbergen","doi":"10.1093/ecco-jcc/jjad212.0484","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0484","url":null,"abstract":"Background Crohn's disease (CD) exclusion diet combined with partial enteral nutrition (CDED+PEN) and exclusive enteral nutrition (EEN) are effective in inducing remission in mild-to-moderate paediatric CD. While tolerance is higher with CDED+PEN than with EEN, a subset of patients still does not achieve remission. Diet-induced remission at week 6 was associated with changes in tryptophan (Trp) metabolism.1 Our aim was to investigate whether baseline Trp metabolites could predict dietary therapy outcomes in paediatric CD. Methods In total, 26 mild-to-moderate treatment-naive paediatric CD patients from a prior randomized controlled trial 2, were classified as having remission 6 (R, n =19 (CDED+PEN=10 and EEN=9)) and No-Remission (NR, n=7 (CDED+PEN=3 and EEN=4)) following 6 weeks of CDED+PEN or EEN therapy, based on the Paediatric Crohn’s Disease Activity Index (PDCAI) score (≤10 remission, >10 no remission). We performed targeted quantitative analysis of 21 tryptophan metabolites in baseline faecal samples from both groups, utilizing liquid chromatography coupled with quadrupole mass spectrometry. Receiving Operator Characteristic Curve (ROC) and Random Forest Analysis were used to assess the predictive power of Trp metabolites for dietary outcomes. Results Baseline clinical characteristics were comparable between R and NR. Baseline fecal kynurenine was significantly higher in NR compared to R for CDED+PEN (p=0.02) (Fig 1A) and EEN (p=0.04) (Fig 2A). ROC analysis highlighted the robust predictive power of kynurenine for CDED+PEN (area under the curve (AUC)=0.97) (Fig 1B) and EEN (AUC=0.88) (Fig 2B) induced remission. Random Forest analysis corroborated these observations. Ratios of Trp metabolites were compared to investigate different downstream Trp pathways. The ratio serotonin/kynurenine was the strongest predictor of CDED+PEN-induced remission (AUC=1) (Fig 1C). The ratio 5-OH-Tryptophan/kynurenine (AUC=0.88) (Fig 2C) predicted EEN-induced remission. When data from CDED+PEN and EEN were combined, kynurenine (AUC=0.91) and the ratios of quinolinic acid/kynurenine (AUC=0.93) and kynurenine/indole-3-acetic acid (AUC=0.88) demonstrated strong predictive performance for dietary therapy in general (Fig 3A,B and C). Conclusion Baseline faecal kynurenine has potential as a prognostic biomarker for dietary therapies. Trp metabolite ratios, notably serotonin/kynurenine for CDED+PEN and 5-OH-tryptophan/kynurenine for EEN, showed promising predictive capabilities. If confirmed in validation studies, baseline faecal Trp markers may be able to provide much needed guidance to personalize dietary intervention within the management of paediatric CD. References 1. Gastroenterology. 2022 Oct;163(4):922-936. 2. Gastroenterology. 2019 Aug;157(2):440-450.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P245 Biologics Sequencing in Clinical Units (BISCUITS): Comparing outcomes in Crohn’s disease patients on second-line biologics","authors":"G Bartalucci, F Taylor, C Gleave, L Dobson, K Bodger, S Dodd, S Bloom, A Passey, R Nissinen, D Wirth, D Andreas, J Lee, J R F Cummings","doi":"10.1093/ecco-jcc/jjad212.0375","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0375","url":null,"abstract":"Background Optimal drug sequencing for patients with Crohn’s disease (CD) who fail first line therapy with TNF-α inhibitors (TNFi) remains unclear. BISCUITS uses validated real world data from the UK IBD Registry (IBDR) to compare outcomes in CD patients who failed first line therapy with TNFi and underwent either a within-class switch (WCS) to an alternative TNFi or an out-of-class switch (OCS) to a different mechanism of action. Methods A feasibility study of 86,000 IBDR patient records identified a potential cohort of 2,678 CD patients who switched from a TNFi to a second biologic. Patients with no other prior IBD diagnosis who switched between 26/08/2015 and 31/03/2021 were included. The primary outcome was time to treatment failure after WCS or OCS, defined as days between initiation of second line (index) biologic and cessation, analysed using unadjusted Kaplan-Meier survival curves & Cox proportional-hazards models. Secondary outcomes included corticosteroid- and surgery- free drug persistence at one year (no drug stop, no steroid treatment or IBD related surgery within 365 days of index), analysed using binary logistic regression adjusting for age at index, early or later treatment with first line TNFi, primary non-response (PNR) or secondary loss of response (SLOR) to first-line TNFi, and immunomodulation therapy at index. Results An initial cohort of seven UK sites contacted, consented, and validated data for 180 patients; demographics and significant differences in case mix are shown in Table 1. Preliminary unadjusted findings suggest that OCS were less likely to discontinue index treatment compared to WCS (hazard ratio (HR): 0.64, 95% Confidence Interval (CI): 0.42 – 0.96, p = 0.03). Subgroup analysis in patients who experienced PNR to their initial TNFi indicated OCS were less likely to discontinue index treatment compared to WCS (HR: 0.25, 95% CI: 0.12 – 0.51, p < 0.001). Conversely, no significant difference in drug persistence was seen in the SLOR group (HR = 0.81, 95% CI: 0.49 – 1.36, p = 0.4), as shown in Figure 1. Binary logistic regression indicated OCS were more likely to show steroid-free drug survival at one year (adjusted odds ratio (aOR): 2.10, 95% CI: 1.10 -– 4.10, p = 0.026), surgery-free drug survival at one year (aOR = 3.31, 95% CI: 1.70 – 6.65, p < 0.001), and steroid- & surgery- free drug survival at one year (aOR = 2.14, 95% CI: 1.13 – 4.10, p = 0.02). Conclusion Real world data from this study shows overall higher drug persistence rates in OCS patients and higher steroid- and surgery- free drug survival at one year. OCS was similarly associated with significantly higher rates of drug survival in patients with PNR, but no significant difference was seen in patients with SLOR.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P915 Multi-Omics Biomarkers for the Prediction of Response to Biologics in Patients with Inflammatory Bowel Disease","authors":"L Chen, C Zhang, R Niu, R Mao, Y Qiu, R Feng","doi":"10.1093/ecco-jcc/jjad212.1045","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.1045","url":null,"abstract":"Background The treatment concept for inflammatory bowel disease (IBD) has been transformed with biologics now recommended as the first-line therapy for moderate-to-severe patients. However, the significant heterogeneity among IBD patients has limited the efficacy of selected biologics based on traditional clinical factors. Therefore, it is imperative to molecularly stratify patients to match them with the most appropriate biologics. In this study, we systematically reviewed baseline omics biomarkers that have the potential to predict response to biological therapies, aiming to facilitate precision medicine in IBD. Methods We conducted a comprehensive literature search using PubMed by which we included studies that explore the role of omics biomarkers in predicting the efficacy of various biologics including anti-TNFα, anti-integrin, anti-IL-12/23P40 and anti-IL-23 P19 in patients with IBD. Results Our review included 110 studies. Of these, 86 studies focused on anti-TNFα, 17 focused on anti-integrin and 7 focused on anti-IL-12/23P40 and/or anti-IL-23P19. These studies investigated multi-levels baseline biomarkers, including genomics, transcriptomics (bulk RNA and sc-RNA sequence), proteomics, microbiome, and metabolomics (derived from serum, urine, or stool). Furthermore, recent studies already focused on integrating multiple omics analysis and showed that the predictive model based on multi-omics data could significantly enhance their performance. Among the available biomarkers, mucosal transcription of OSM (AUROC = 0.83), IL-13RA2 (AUROC = 0.90), and TREM-1 transcription in mucosal biopsy (AUROC = 0.77) as well as in PBMC ( AUROC varies between 0.78 and 0.94) could accurately predict the response to anti-TNFα. The mucosal IL-23A transcription could discriminate responders from non-responders to anti-IL-12/23P40 with an AUROC of 0.90. OSM, biomarkers of intestinal collagen turnover like C4M, IL-17, IL-22, and TNFα in serum also showed significant potential in predicting the response to anti-TNFα, anti-integrin and anti-IL-12/23P40. In addition, single-cell molecular signatures with sc-RNA sequencing provided more profound insights into predicting the response to biologics. The lack of reproducibility in results across different groups may be due to the disparity in patient selection, methodology, and study designs among different investigations. Conclusion Numerous omics markers have shown great potential in predicting the efficacy of biologics. However, it is crucial to explore and validate these novel biomarkers in larger cohorts using harmonized protocols to facilitate their evaluation into actual clinical practice, especially for newer biologics like anti-IL-12/23P40 and anti-IL-23P19.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}