Journal of Crohn's and Colitis最新文献

{"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":"30 1","pages":""},"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":"34 1","pages":""},"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":"121 1","pages":""},"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":"120 1","pages":""},"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}

{"title":"P1200 Study of correlation between polymorphisms of vitamin D metabolism genes and perianal disease in Crohn's disease","authors":"D G Ribaldone, C Cafasso, M Antonucci, A Palermiti, G P Caviglia, M Vernero, A D'Avolio, J Cusato","doi":"10.1093/ecco-jcc/jjad212.1330","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.1330","url":null,"abstract":"Background Vitamin D (VD) is a fat-soluble vitamin essential for calcium homeostasis and that acts at the extraskeletal level. UVB skin exposure allows the synthesis of provitamin D. This undergoes a first hydroxylation in the leaver by the CYP2R1 enzyme and a second hydroxylation in the kidney by the CYP27B1 enzyme: active VD is obtained. VD is transported into the circulation by VDBP and exerts its activity in the target cells binding its VDR receptor. Finally, VD is inactivated by the renal enzyme CYP24A1. Perianal disease (pCD) is a severe phenotypic manifestation of CD that may present as perianal fistula, abscess, recto-vaginal fistula, or stenosis. Among the mechanisms involved in its pathogenesis we recognise local inflammation and intestinal microbiota alteration. Vitamin D (VD) seems to act on these elements. As there are currently no studies on this subject in the literature, the aim of this study is to evaluate the presence of an association between SNPs of genes coding for enzymes, transporters and receptors involved in the VD pathway and the occurrence of pCD in CD patients. Methods The study was carried out on the biological samples of 206 patients with CD, including 34 with pCD, who were followed up at the inflammatory bowel disease clinic in Turin, Italy. Through the use of Real-Time PCR, the genotype distribution of the following genes were assessed: VDR, CYP27B1, CYP24A1, and GC. For the association study, chi-square test was performed with calculation of p value and, when significant, logistic regression and calculation of OR with 95% CI was performed. Results Studying the association between SNPs and the presence of pCD, the following results were obtained: BsmI p=0.0470 and Apal p=0.0251. For BsmI heterozygous genotype there was an OR=2.5 (95% CI 1.2-5.3) of developing perianal disease and p value=0.02, while for ApaI heterozygous there was OR=2.91 (95% CI 1.3-6.6) of presenting pCD, with p value=0.01. Conclusion In the literature, there are several studies examining the association between the heterozygous Aa genotypes of ApaI and Bb genotypes of BsmI and increased inflammatory markers. In addition, some studies suggest that these two genotypes represent a risk factor for some diseases, including multiple myeloma, systemic lupus erythematosus, and mild cognitive disorder. This study demonstrates for the first time an impact of polymorphisms of genes associated with the VD pathway in predicting the onset of pCD. Specifically, the presence of the heterozygous genotype of BsmI and ApaI significantly increases the risk. Future studies need to be performed in different and larger cohorts of patients in order to confirm these data.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559499","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":"P947 medical cannabis increases appetite but not body weight in patients with inflammatory bowel diseases","authors":"N. Fliss Isakov, C. Seidenberg, D. Meiri, M. Yackobovitch-Gavan, N. Maharshak, A. Hirsch","doi":"10.1093/ecco-jcc/jjad212.1077","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.1077","url":null,"abstract":"\u0000 \u0000 \u0000 Medical cannabis (MC) is prescribed to improve appetite and nutritional status in patients with inflammatory bowel diseases (IBD) despite no supporting evidence. We aimed to describe the effect of MC on appetite and dietary intake among patients with IBD.\u0000 \u0000 \u0000 \u0000 An observational prospective cohort study, among patients with IBD, initiating treatment with MC for disease related symptoms, at the IBD clinic of a tertiary referral medical center. Patients' demographics, anthropometric measurements, medical history, cannabis use history, and medical treatment were documented and an appetite questionnaire (SNAQ), and food frequency questionnaire (FFQ) were filled before MC initiation and throughout 6 months of treatment.\u0000 \u0000 \u0000 \u0000 Of patients enrolled in the study (n=149, age 39.0±14.1 years, 42.3% female) and treated with MC for disease related symptoms, on top of their routine therapy regimen, while 33.6% received MC for increasing appetite and improving nutritional status. Among patients treated for raising appetite and improving nutritional status, 34.0% experienced a significant increase in appetite after 3 months. None the less, all patients experienced a modest increase in appetite (P<0.05), a trend which was more profound among patients treated with high THC/CBD ratio (SNAQ score 27.0±4.1 at 3 months vs. 25.2±3.6 at baseline, P=0.021). Nonetheless, this increase in appetite throughout the study did not result in increased energy, macronutrient intake or in BMI following MC treatment. Among patients without a significant increase in appetite by 3 months of MC therapy, a significant decrease in BMI was noticed at 6 months (24.1±3.7 at baseline vs. 23.4±3.6 at 6 months, Pv=0.010).\u0000 \u0000 \u0000 \u0000 Use of MC, and specifically THC, may be a potential strategy to improve appetite among some patients with IBD. This increase in appetite was not associated with an increase in caloric intake or in BMI at follow-up.\u0000","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"31 28","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139631126","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":"P950 Advancing Precision Nutritional Assessment in Inflammatory Bowel Disease (IBD): Adding Fecal Calprotectin in the Malnutrition Inflammation Risk Tool (MIRT) score","authors":"P. Dhoble, D. Desai, P. Abraham, T. Gupta, V. Dharap, M. Kutar","doi":"10.1093/ecco-jcc/jjad212.1080","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.1080","url":null,"abstract":"\u0000 \u0000 \u0000 Most of the nutritional assessment tools assess only nutrition. The Malnutrition Inflammation Risk Tool (MIRT) incorporates both malnutrition and inflammation (CRP).1 However, CRP is a less sensitive biomarker than fecal calprotectin for the assessment of inflammation. Adding fecal calprotectin (FC) in the MIRT score may improve the assessment of malnutrition risk. FC level cutoff of < 250 mg/kg in adults correlate with endoscopic remission with good sensitivity and specificity.2 Fecal calprotectin level greater than 800 µg/g is predictive of a need for rescue therapy.3\u0000 \u0000 \u0000 \u0000 To study if adding fecal calprotectin to CRP by improves the yield of MIRT score\u0000 \u0000 \u0000 \u0000 This is a single center, prospective, cohort study including consecutive patients with IBD (Ulcerative colitis {UC} and Crohn’s disease {CD}). Malnutrition was defined as per European society for clinical nutrition and metabolism (ESPEN guidelines): BMI <18.5 kg/m2 or unintentional weight loss >10% (indefinite time). MIRT score was calculated with BMI, weight loss and CRP and MIRT-FC by adding FC to CRP with as shown in the table below:\u0000 \u0000 \u0000 \u0000 During 2019 to 2021, 200 patients included, median age 39 years (IQR 28-53) (105 UC, 93 CD and 2 IBD-U), 60 (30%) patients had malnutrition (32 UC, 26 CD and 2 IBD-U and 27 (45%) malnourished IBD patients had MIRT score > 3. CRP values were normal in 30 (50%). Adding fecal calprotectin to MIRT score malnourished IBD patients, 46 (76%) malnourished IBD patients had MIRT score > 3 (P=0.005). This modification (MIRT FC) increased the yield of existing MIRT score by 31%.\u0000 \u0000 \u0000 \u0000 MIRT-FC score improved the yield of MIRT score. Prospective studies are required to validate this further.\u0000 References:\u0000 1. Jansen I, Prager M, Valentini L, Büning C. Inflammation-driven malnutrition: a new screening tool predicts outcome in Crohn’s disease. British Journal of Nutrition. Cambridge University Press; 2016;116(6):1061–7.\u0000 2. D'Haens G, Ferrante M, Vermeire S, et al. Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflamm Bowel Dis 2012; 18:2218-2224.\u0000 3. Sasidharan S, Sasson AN, Shannon KM, Ananthakrishnan AN. Fecal Calprotectin Is a Predictor of Need for Rescue Therapy in Hospitalized Severe Colitis. Inflamm Bowel Dis. 2022;28(12):1833-1837.\u0000","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139631198","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":"P1061 TEV-48574, an anti-TL1A antibody in development for use in IBD, is safe and well tolerated following 16 weeks of subcutaneous treatment in adults with severe uncontrolled T2-low/non T2 asthma","authors":"G. Raphael, G. Damera, T. Angeles, S. Li, S. Stoyanov","doi":"10.1093/ecco-jcc/jjad212.1191","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.1191","url":null,"abstract":"\u0000 \u0000 \u0000 TEV-48574 is a human antibody that targets tumor necrosis factor (TNF)-like ligand 1A, also known as TNF superfamily member 15 (TNFSF15). It is in clinical development as a potential treatment for ulcerative colitis (UC) and Crohn’s disease (CD). TL1A signalling is believed to amplify immune-mediated inflammation in asthma and inflammatory bowel disease (IBD); thus, targeting TL1A may mitigate over-activation of immune responses. A proof-of-concept phase 2A study evaluated safety, tolerability and efficacy of TEV-48574 as treatment for adults with severe uncontrolled asthma (Clinicaltrials.gov NCT04545385). Although the study terminated (after meeting pre-specified criteria for futility at a preplanned interim analysis) the drug demonstrated favourable safety, tolerability and immunogenicity data, supporting the potential use of anti-TL1A treatment in patients with UC and CD.\u0000 \u0000 \u0000 \u0000 TEV-48574 was administered as a loading dose followed by 7 maintenance doses given subcutaneously (sc) every 2 weeks for 16 weeks in adult patients (n = 65) with severe T2-low asthma with no/low inflammation at baseline. The primary efficacy endpoint was reduction in patients who experience loss of asthma control (LoAC). Patients were monitored for LoAC at bi-weekly visits and daily by use of a handheld spirometer/e-diary. Safety was assessed throughout the study.\u0000 \u0000 \u0000 \u0000 Of 65 randomized patients, 64 received at least one dose of study drug and were included in the safety analysis (33 active drug; 31 placebo). There were no severe AEs, treatment related SAEs, deaths, or withdrawals due to adverse events, and no medical device-related issues. There were no clinically meaningful changes in lab parameters, vital signs or ECGs. Furthermore, there was no evidence of immune suppression, opportunistic infections, or malignancies. Mild treatment-related adverse reactions occurred in both treatment groups (erythema and pruritus in two placebo patients; erythema in one TEV-48574 treated patient). Mild injection site reactions occurred more frequently (not statistically different) in the TEV-48574 group. Treatment-emergent anti-drug antibodies were reported in patients taking TEV-48574 (3 patients; 9.09%), with no anaphylactic or severe systemic reactions.\u0000 \u0000 \u0000 \u0000 Overall, TEV-48574 administered every 2 weeks over 16 weeks demonstrated a favourable safety and tolerability profile with no emerging safety signals or evidence of immunosuppression. This is consistent with TL1A being an amplifier of inflammation. Treatment with TEV-48574 may dampen excessive inflammation without inducing a state of immunodeficiency in patients with conditions such as UC or CD, supporting further development in these indications.\u0000","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"5 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139631418","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":"P350 Development of consensus statements for transitional care for adolescents with Inflammatory bowel disease throughout Australia and New Zealand","authors":"A. Vernon-Roberts, P. Chan, B. Christensen, R. Havrlant, E. Giles, A. Williams","doi":"10.1093/ecco-jcc/jjad212.0480","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0480","url":null,"abstract":"\u0000 \u0000 \u0000 The incidence of paediatric inflammatory bowel disease (IBD) is rising, and as such there is an increasing need to support adolescents with IBD as they from transition from paediatric to adult care. The use of a structured process for transition is well supported in the literature, however, variation in the delivery of transitional care for adolescents with IBD has been identified across Australis and New Zealand. The aim of this study was to develop consensus statements, based on evidence and expert opinion, to guide transitional care services in IBD.\u0000 \u0000 \u0000 \u0000 The consensus statements were developed using a modified UCLA-RAND methodology. An IBD expert steering committee was formed, and then a systematic literature review conducted to grade the available evidence and inform initial development of consensus statements. A multi-disciplinary group was formed comprising 16 participants [clinicians, nurses, surgeons, psychologists], that voted anonymously on the level of appropriateness and necessity for each consensus statement, as well as provided general feedback for each. Scoring was facilitated using Likert scales [1=lowest, 9=highest] with a median ≥7 required for inclusion.\u0000 \u0000 \u0000 \u0000 Fourteen consensus statements were devised by the Steering committee (Table 1). Key recommendations including the use of a structured transition programme and transition coordinator. Statements recommended assessment of mental health and transition readiness, and outlined discussion points regarding lifestyle, environment and psychosocial factors to be held with adolescents. The importance of allied health input, the age for transition, recommendations for clinical communication and handover were highlighted, as well as considerations for individual patients. In the first voting round by the multi-disciplinary group each statement reached a median score of ≥ 8 for appropriateness, and ≥7 for necessity. An online meeting with both groups was held to discuss voting results and refine statements.\u0000 Table 1. Final consensus statements to guide transition of children with inflammatory bowel disease in Australasia.\u0000 \u0000 \u0000 \u0000 \u0000 There is an identified need for guidance in paediatric to adult transitional care for adolescents with IBD. Consensus statements were developed by a multi-disciplinary group, supported by published evidence, to provide this guidance. The planned publication of the consensus process and statements will facilitate standardize delivery of IBD transitional care within Australasia.\u0000","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"24 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139631470","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":"P566 Maintenance vedolizumab treatment in pediatric IBD: 54-week follow-up of the prospective multicenter VEDOKIDS study","authors":"O. Atia, Z. Shavit-Brunschwig, G. Focht, R. Lev-Tzion, R. Stein, E. Broide, D. Urlep, J. Hyams, B. Weiss, M. Aloi, A. Assa, R. Russell, D. Turner","doi":"10.1093/ecco-jcc/jjad212.0696","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0696","url":null,"abstract":"\u0000 \u0000 \u0000 Prospective long-term data on vedolizumab (VDZ) in children with Crohn’s disease (CD) and ulcerative colitis (UC) are lacking. In this prospective, multicenter cohort study, we aimed to evaluate the effectiveness and safety of maintenance therapy with VDZ in pediatric CD and UC.\u0000 \u0000 \u0000 \u0000 Children commenced on VDZ were followed at baseline and 2, 6, 14, 30 and 54 weeks thereafter. Serum for drug levels and stool for calprotectin were repeatedly obtained. The primary outcome was sustained steroid-free remission (SSFR), defined as clinical remission )PUCAI<10 or wPCDAI<12.5) without steroids/EEN at both 30 and 54 weeks, analyzed under the ITT principle.\u0000 \u0000 \u0000 \u0000 139 children were enrolled (77 [55%] UC, 62 [45%] CD; age 14.9 years (IQR 12.0-16.6). Of the 119 (86%) children >30kg, 110 (92%) received a dose of 300mg; 20 (14%) weighed<30 kg and received a dose of 8.3mg/kg (IQR 7–10.3). Week-54 remission rate was 52% in UC and 37% in CD; SSFR rates were 42% and 24%, respectively (OR 2.2 [95%CI 1.1-4.7] Figure). SSFR rate was numerically higher in isolated colonic CD than in ileal disease (5/11 [45%] vs 10/49 [20%], OR 3.3 [95%CI 0.8-12.9]; p=0.08). Infusion interval was shortened in 22 children (10 [13%] UC, 12 [19%] CD), of whom none achieved SSFR.\u0000 SSFR rate was higher in week-6 responders compared to non-responders in UC (51% vs 27%, OR 2.9 [1.1-7.7]) and CD (35% vs 14%, OR 3.4 [95%CI 0.95-12.4]), similar to the week-14 figures (UC: 50% vs 22%, OR 3.6 [1.2-11.1]; CD: 36% vs 8%, OR 6.2 [1.3-30.8]). SSFR was eventually achieved in 49% of UC children having mild disease at week-6 and 14% with moderate-severe disease (OR 5.8 [95%CI 1.2-28.2]); the corresponding rates in CD were 31% and 0% (p=0.02).\u0000 In multivariable models, the best predictors in CD were lower wPCDAI at baseline (AUROC 0.88 [95%CI 0.79-0.96]; optimal cutoff 25 (sens/spec 76%/80%)) and at week 6 (0.90 [0.82-0.98]; optimal cutoff 17.5 (80%/87%)). In UC, the best predictors were PUCAI at week 6 (0.70 [0.57-0.82]; optimal cutoff 10 (64%/57%)) and at week-14 (0.78 [0.67-0.89]; optimal cutoff 5 (76%/60%; Table).\u0000 In children <30kg, SSFR was associated with week 6 drug levels >30ug/mL, not reaching statistical significance (3/6 [50%] vs 1/8 [13%], OR 7.0 [95%CI 0.5-97]). By week 54, 197 adverse events were recorded, of which were VDZ-related in 8 (5.8%) children, and in 2 (1.4%) led to stopping VDZ; none were severe. There was 1 lymphoma case judged to be unrelated to VDZ.\u0000 \u0000 \u0000 \u0000 VDZ was effective for maintaining remission, more so in UC and in colonic CD. The likelihood of eventually achieving SSFR was very low in children with moderate-severe disease or those not showing response at week-6, particularly in CD.\u0000 \u0000 \u0000","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"22 24","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139631499","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}