Journal of Crohn's and Colitis最新文献

{"title":"New surgery and hospital-diagnosed infections in elderly patients with inflammatory bowel disease undergoing surgery - a nationwide cohort study","authors":"Bente Mertz Nørgård, Olav Sivertsen Garvik, Floor Dijkstra Zegers, Jan Nielsen, Ken Lund, Torben Knudsen, Jens Kjeldsen","doi":"10.1093/ecco-jcc/jjae047","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjae047","url":null,"abstract":"Background Elderly patients with inflammatory bowel disease (IBD) are fragile in many aspects. Therefore, in these patients, we studied post-operative complications (new abdominal surgery and serious infections after the first IBD surgery). Methods This is a nationwide cohort study based on Danish health registries and included patients with IBD undergoing surgery. The study population was split into ulcerative colitis (UC) and Crohn’s disease (CD). The exposed cohort (elderly) constituted those at an age of ≥ 60 years at first IBD surgery, and the unexposed (adults) those with surgery at the age of 18-59 years. We estimated adjusted Hazard Ratios (aHR) of a) new abdominal surgery within 2 years, and b) serious (hospital-diagnosed) infections within 6 and 12 months. We adjusted for several confounders including type of index surgery (laparoscopic or open). Results The aHR for a new surgery among elderly with UC and CD were 0.69 (95% CI 0.58-0.83) and 0.98 (95% CI 0.83-1.15), respectively. In elderly with UC, the aHRs of infections within 6 and 12 months after surgery were 1.07 (95% CI 0.81- 1.40) and 0.85 (95% CI 0.67-1.08), respectively. In the elderly with CD, the aHRs of infections within 6 and 12 months were 1.45 (95% CI 1.12-1.88) and 1.26 (95% CI 1.00-1.59), respectively. Conclusion The elderly with IBD did not have an increased risk of new abdominal surgery within two years of the first surgery. Elderly with CD, but not UC, had an increased risk of serious infections within 6 months of surgery.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140596556","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":"Fecal Microbiota Transplantation engraftment after budesonide or placebo in patients with active ulcerative colitis using pre-selected donors: a randomized pilot study","authors":"Emilie van Lingen, Sam Nooij, Elisabeth Terveer, Emily Crossette, Amanda Prince, Shakti Bhattarai, Andrea Watson, Gianluca Galazzo, Rajita Menon, Rose Szabady, Vanni Bucci, Jason Norman, Janneke van der Woude, Sander van der Marel, Hein Verspaget, Andrea van der Meulen – de Jong, Josbert Keller","doi":"10.1093/ecco-jcc/jjae043","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjae043","url":null,"abstract":"Background Fecal microbiota transplantation (FMT) shows some efficacy in treating patients with ulcerative colitis (UC), although variability has been observed among donors and treatment regimens. We investigated the effect of FMT using rationally selected donors after pretreatment with budesonide or placebo in active UC. Methods Patients ≥ 18 years old with mild to moderate active UC were randomly assigned to three weeks budesonide (9 mg) or placebo followed by four weekly infusions of a donor feces suspension. Two donors were selected based on microbiota composition, Treg induction and SCFA production in mice. The primary endpoint was engraftment of donor microbiota after FMT. In addition, clinical efficacy was assessed. Results In total, 24 patients were enrolled. Pretreatment with budesonide did not increase donor microbiota engraftment (p=0.56) nor clinical response, and engraftment was not associated with clinical response. At week 14, 10/24 (42%) of patients achieved (partial) remission. Remarkably, patients treated with FMT suspensions from one donor were associated with clinical response (80% of responders, p<0.05) but had lower overall engraftment of donor microbiota. Furthermore, differences in the taxonomic composition of the donors and the engraftment of certain taxa were associated with clinical response. Conclusion In this small study, pretreatment with budesonide did not significantly influence engraftment or clinical response after FMT. However, clinical response appeared donor-dependent. Response to FMT may be related to transfer of specific strains instead of overall engraftment, demonstrating the need to characterize mechanisms of actions of strains that maximize therapeutic benefit in ulcerative colitis.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140596311","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":"P611 Relation between AntiTNF levels during the induction and clinical and radiological outcomes in perianal Crohn´s disease","authors":"C Amiama Roig, C Suarez Ferrer, E Martin Arranz, J L Rueda Garcia, M Sánchez Azofra, J Poza Cordón, I Gonzalez Diaz, C Amor Costa, M D Martín-Arranz","doi":"10.1093/ecco-jcc/jjad212.0741","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0741","url":null,"abstract":"Background Perianal Crohn's disease(PCD) significantly impacts quality of life with poor long-term prognosis. Anti-tumor necrosis factor(anti-TNF) therapy improves fistula closure rates. However, achieving permanent closure remains challenging. Our aim is to evaluate the relation between antiTNF(infliximab (IFX) and adalimumab(ADA) serum concentrations at induction(w2 and 6), and clinical and radiological outcomes at w24 and w52 Methods We conducted a single tertiary center, retrospective, cohort study including patients with an established diagnosis of PCD treated with antiTNF because of perianal activity. Variables related to their PCD(phenotype, location, fistulas type) were collected. Regarding treatment, we collected serum levels at week 2,6,24 and 52, concomitant treatment and setons presence. We defined clinical response as the absence of drainage on physical examination and clinical remission as the absence of external fistula openings. Radiological response was defined as the absence of T2 hypersignal, gadolinium enhancement, abscess and proctitis in pelvic MRI Results 65 patients were included, baseline characteristics are in Table1. None of the demographic characteristics collected were statistically significant related to clinical or radiological response although non smokers(p=0.01), ileal(p=0.02) and non-stricturing disease(p=0.01) had statistically significant higher drug levels. Taking into account the clinical response at w52, IFX mean levels at w2 were 25.8µg/mL(SD 4.1) in non responders and 30.9µg/mL(SD 14) in responders(p=0.39). At w6 they were 17.2µg/mL(SD 12.2) and 19.4µg/mL(SD 13.8) respectively(p=0.7). ADA mean levels at w2 were 13.3µg/mL(SD 7.7) in non responders and 14µg/mL(SD 6.3) in responders(p=0.87). At w6 they were 10.1µg/mL(SD 3.3) and 12µg/mL(SD 6.1) respectively(p= 0.59). For radiological response at w52 IFX mean levels at w2 were 27µg/mL(SD 15.3) in non responders and 32.7µg/mL(SD 14.5) in responders(p=0.45). At w6 the mean levels were 15.9µg/mL(SD 6.7) and 23.7µg/mL(SD 14.8) respectively(p=0.27). In ADA group the mean levels at w2 were 14.8µg/mL(SD 7.6) in responders and only one patient did not respond. At w6 ADA mean levels were 12.3µg/mL(SD 5.9) in non responders and 12.7µg/mL(SD 6.2) in responders(p=0.94). Early response at w24 was related with a long-term response at w52, 89.9% of the patients who responded at w52, had already responded at w24. Conclusion In our study we observed that almost 90% of the patients who had an early response also responded at w52, so trying to achieve an early response should be an aim in clinical practice. Despite the limited number of patients, our study shows a trend in the relationship between higher antiTNF levels and clinical and radiological response rates","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":"139559212","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":"P425 Clinical Characteristics of Steroid-Dependent Ulcerative Colitis Patients after Acute Severe Ulcerative Colitis Treatment in East Asia and Australia/New Zealand: AOCC and ANZIBDC collaboration study","authors":"D H Kim, S H Park, H S Kim, S J Kim, K O Kim, Y J Lee, E M Song, E S Kim, H S Lee, Y K An, J Begun, L Ruddick-Collins, R Fernandes, J Liu, Q Cao, T Kobayashi, S C Wei","doi":"10.1093/ecco-jcc/jjad212.0555","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0555","url":null,"abstract":"Background Intravenous steroid therapy (IVS) is the main initial treatment for acute severe ulcerative colitis (ASUC). The study aimed to assess corticosteroid dependency after treating ASUC and to explore potential differences between East Asian and Caucasian populations within the steroid-dependent group. Methods Patients from East Asia (China, Japan, South Korea, and Taiwan) and Australia/New Zealand diagnosed with ASUC based on the Trulove and Witts criteria from January 2015 to September 2022 were retrospectively included in the study. We specifically chose individuals responsive to intravenous corticosteroid treatment and divided them into two groups based on steroid dependency. \"Steroid dependency\" was defined as the inability to reduce steroid medication to a dosage below 10 mg/d (equivalent to prednisolone) within three months of initiating steroid treatment or experiencing a relapse within three months of discontinuing steroid therapy. Patients with a history of biologics or small molecules and those currently receiving them were excluded. Results Among 861 patients with ASUC (430 from East Asia and 431 from Australia/New Zealand), 626 received initial IVS, and 381 showed steroid response. Among these steroid responders, 102 patients (26.7%) were classified as steroid-dependent with no significant difference between East Asians and Caucasians (28.3% vs. 24.1%, p=0.44). For 1 year after ASUC, the colectomy rate (7.8% vs. 2.9%, p=0.04) and ASUC relapse rate (18.6% vs. 10.2%, p=0.03) were higher in the steroid-dependent than non-dependent group. For the management of steroid dependency, East Asians mainly repeated steroid treatment (60.9%), while Caucasians mostly switched to infliximab (57.1%). In the Cox regression analysis of 3-year follow-up data for the steroid-dependent group, Caucasians showed a significant increase in colectomy rates (adjusted hazard ratio [aHR] 1.59, 95% confidential interval [CI] 1.12-2.25, p<0.01) compared to East Asians. Additionally, relapse rates increased in Caucasians (aHR 1.37, 95% CI 1.13-1.65, p<0.01), while relapse rates decreased in thiopurine users (aHR 0.32, 95% CI 0.12-0.87, p=0.03). Conclusion Around one-fourth of patients with ASUC who initially responded to IVS became steroid-dependent. East Asians showed a more favorable prognosis compared with Caucasian in this steroid-dependent group.","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":"139559389","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":"P144 Modulation of Immunometabolism via NLRX1 or PLXDC2: Novel Bimodal Mechanisms for the Treatment of Inflammatory Bowel Diseases","authors":"S Danese, J F Colombel, F Rieder, L Peyrin-Biroulet, B Siegmund, S Vermeire, M Dubinsky, S Schreiber, A Yarur, R Panaccione, B Feagan, R Mosig, F Cataldi, B Verstockt","doi":"10.1093/ecco-jcc/jjad212.0274","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0274","url":null,"abstract":"Background Immunometabolism exerts a bimodal action at the interface of extracellular immune response and intracellular metabolism. It controls both intracellular processes and extracellular inflammatory responses by regulating both cellular energy supply & demands, factors that determine how a cell responds to the extracellular signals. Hence, immunometabolic pathways represent an attractive target as a gate of entry & checkpoint for the inflammatory cascade. Nucleotide-binding oligomerization domain, Leucine Rich repeat containing X1 (NLRX1) & PLeXin Domain-Containing protein 2 (PLXDC2) have been identified in immunometabolic pathways for multiple cell types in immune mediated inflammatory diseases (IMIDs) and inflammatory bowel diseases (IBD)2,3. The goal of this analysis was to compare these two key immunometabolic pathways. Methods For both programs, in vitro murine T cell & macrophage differentiation & in vivo mouse dextran sodium sulfate (DSS) colitis models, gene expression, metabolic profiles & cytokine expression were assessed. Results NX-13, a novel NLRX1 agonist, resulted in regulation of cellular metabolism: activation of mitochondrial genes such as mt-nd3 & odgh, and concomitant down-regulation of glucose uptake by murine T cells (Fig1A). Simultaneously, NLRX1 stabilization by NX-13 increased antioxidant enzyme expression & reduced reactive oxygen species in T cells. NX-13 specifically reduced effector T cell differentiation (Fig1B) & inflammatory cytokine expression, while Treg differentiation was increased. Ultimately, these bimodal effects converge to dampened colitis severity scores in acute DSS colitis (Fig1C). PLXDC2 activation by LABP-69 directly reduced glycolysis, reflected by decreased extracellular acidification & oxygen consumption in bone marrow-derived macrophages (BMDM) stimulated with lipopolysaccharide (LPS, Fig1D). LABP-69 also reduced superoxide levels in BMDM. Of note, PLXDC2 activation downregulated cellular expression of the inflammatory cytokines TNFα & IFNγ by T cells (Fig1E). The PLXDC2 agonist PX-04 decreased inflammation in acute DSS colitis in mice as shown by disease activity score (Fig1F). Conclusion Agents targeting immunometabolism demonstrate a novel, innovative concept with potential therapeutic applicability in IBD & other IMID. NLRX1 & PLXDC2 represent distinct pathways that modulate the intracellular metabolic state simultaneously with extracellular inflammation and hence can be targeted to break the inflammatory cascade to stop chronic inflammation. These bimodal MOAs will be studied further to understand how they may synergistically address multiple aspects of chronic immune diseases such as IBD. 1Chi Cell Mol Immunol (19) 2Leber et al. J Immunol 203(12) 3Tubau-Juni et al. J Immunol 206(Supp)","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":"139559427","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":"DOP26 Metagenomic and metabolomic profiles in IBD: understanding microbial and metabolic shifts from a large deeply phenotyped cohort","authors":"B Marius, N Rolhion, L Creusot, A Lefevre, I Alonso, L Brot, C Danne, A Bourrier, L Parrot, D Mélanie, N Benech, I Nion-Larmurier, P Mclellan, C Landman, L Beaugerie, P Seksik, P Emond, J Kirchgesner, H Sokol","doi":"10.1093/ecco-jcc/jjad212.0066","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0066","url":null,"abstract":"Background Alterations in gut microbiota composition and functions are involved in the pathogenesis of Inflammatory Bowel Disease (IBD) and the role of specific bacterial taxa has been particularly pointed out. The role of microbiota-derived metabolites, including those produced from tryptophan, are major actors in host-microbiota interactions in health and in IBD. Large studies analyzing both gut microbiota and metabolomics data are scarce. Methods In the current study, we analyzed a total of 764 individuals from Saint Antoine Hospital cohort, including 447 patients with Crohn's disease (CD), 262 patients with Ulcerative Colitis (UC) and 55 healthy subjects. We performed shotgun metagenomic sequencing on fecal samples and integrated the results with deep clinical phenotyping and targeted metabolomics data encompassing 294 different molecules. Results We observed strong changes in the taxonomic composition and functional capabilities of the microbiota in CD and UC patients compared to healthy subjects. Besides disease itself, the most important drivers of microbiota composition were the disease location (Montreal classification), recent antibiotic treatment, disease activity (flare vs remission) and history of ileocecal resection. Interestingly, IBD diagnosis explained much more the variations of microbiota functions than taxonomy. The decrease in microbiota diversity was stronger in CD than in UC. In parallel to a decreased amount of Faecalibacterium in IBD, we also observed a decrease in the diversity of Faecalibacterium strains, with a stronger decrease in CD. Our multifactorial analysis revealed specific microbial taxa and functions affected by disease-related factors. We particularly identified many correlations between tryptophan metabolites and microbial abundance. Targeted gene analysis of tryptophan-related enzymes in metagenomes further supported these findings. A network analysis considering bacterial taxa and metabolites revealed profound alterations in IBD with some specificities between CD and UC. Conclusion We pointed out new microbiome and metabolome alterations associated with IBD, with some phenotype specificities. Overall, our findings provide crucial information and a substantial resource for understanding the interactions between the host and microbiome in the context of IBD.","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":"139559729","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":"P424 Analysis of the intestinal microbiome using an Endoscopic Brush in Ulcerative colitis","authors":"B Lee, B Keum, S Kim, H Jeon, Y Jeen, C Hoonjai","doi":"10.1093/ecco-jcc/jjad212.0554","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0554","url":null,"abstract":"Background The precise pathogenesis of the Ulcerative colitis is still yet unknown, but one of its cause is known to be microbial dysbiosis. The mucosa-associated microbiota are more deeply involved in the pathogenesis of UC. However, the optimal sampling of mucosa-associated microbiome has yet to be investigated. In this study, we investigated the mucosa-associated microbiome in patients with ulcerative colitis, using endoscopic brush samples. We hypothesized that endoscopic brushing is precise and noninvasive method to get sample of mucosa-associated microbiome. Methods Patients with UC who visited the gastroenterology department of Korea University Anam hospital were screened for this study. Clinical data such as medical records, colonoscopy and fecal samples were reviewed. Using a stool and saliva sample collector kit respectively, the subjects provided stool and saliva samples. Brushing samples were collected during the sigmoidoscopy procedure with 3-4 brush strokes on the colon mucosa using the cytology brush. The samples were analyzed for microbiome in the Korea University Medical Center. Results From July 2022 to January 2023, we prospectively enrolled 19 patients with UC. Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria were the most common species in microbiota of brush, stool and saliva.(Fig.1-1) The microbiome between stool and brush was no significant difference in alpha and beta diversities.(Fig.1-2) However, Oral microbiome was different from stool and brush in beta diversities.(Fig.1-3) Patients were categorized into to analyze the oral microbiome. A trend was observed where increased disease severity was associated with an increase in Firmicutes.(Fig.1-4) Conclusion The microbiome of stool and brush was no significantly different. However, the novel sampling of mucosa-associated microbiome, endoscopic brush, is not inferior compared to currently used sampling of stool. Also the analysis of the oral microbiome suggested that Firmicutes could be considered a useful biomarker for assessing disease severity. Therefore, it is necessary to conduct followup research by increasing the number of subjects.","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":"139559193","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":"P706 Tofacitinib in Moderate to Severe Ulcerative Colitis patients naïve to biological therapy: A prospective real world analysis of efficacy and safety","authors":"R Banerjee, M Dhanush, N Raghunathan, P Pal, V Joshi, R Patel, S Godbole, Y Akki, S Valluri, P Nagasuri, A Haridas","doi":"10.1093/ecco-jcc/jjad212.0836","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0836","url":null,"abstract":"Background Tofacitinib is an oral non-selective Janus Kinase inhibitor approved for Ulcerative colitis (UC) after the failure of biological therapy. Tofacitinib as first line therapy in biologic naive patients has not been evaluated. Methods We conducted a prospective study to assess the safety and efficacy of Tofacitinib as first line therapy in biologic naive moderate to severe UC. Tofacitinib was given at a dose of 10mg BD for 8 weeks followed by de-escalation to 5mg BD maintenance in responders. Dose escalation was done for relapses. Demographics, disease characteristics, concomitant medication, adverse events, severity and time to relapse were recorded. Clinical response and remission (defined as partial Mayo score: PMS decrease ≥2 and PMS ≤1 respectively) were measured at 4 weeks, 8 weeks, 24 weeks and 52 weeks. Endoscopic response (UCEIS score decrease ≥2) and remission (UCEIS 0-1) were assessed at 1 year. Time to event analysis was done to evaluate the cumulative rate of clinical response. Results 176 patients (136 biologic naive, 58% male; median age 40y [IQR:31-48y]) were included. Median baseline PMS and UCEIS score were 5 (IQR: 5-7 and 4-6 respectively) (Table 1). Of the biologic naïve cohort, clinical response was achieved in 68.4% and 79.4% at 4 and 8 weeks respectively. Clinical remission was achieved in 45.6%(4-weeks) and 55% (8-weeks). Maintenance of remission was seen in 44.1% and 32.4% in 24 and 52 weeks respectively (Fig1A). There was a significant reduction in PMS from baseline to end of 8-weeks (p<0.001) (Fig 1B). Corticosteroid-free clinical remission was achieved in 64.8% at 24-weeks. 106 patients (77.9%) maintained response till last follow-up. 11 relapsed after dose de-escalation (median time of 5m [range 3-22m]. 7/11 responded to dose escalation to 10mg. Endoscopic response was noted in 62.5% and remission in 33.9% with significant reduction in UCEIS from baseline to 52-weeks(p<0.001) (Fig 1B). Severe and minor adverse events were noted in 4 and 3 patients respectively (Table 1). Overall 1/3 of patients discontinued therapy at 24-weeks (14%) and 52 weeks (10%). No significant difference in proportion of clinical or endoscopic remission was observed between the biologic naïve and those with history of prior biologic usage (n=31, median time from withdrawal of biologics to Tofacitnib initiation=9 months). Conclusion Tofacitinib was effective in induction of clinical remission in more than half of biologic naive, moderate to severe UC . Three-fourth of these patients continued to be in remission at one year with few serious adverse events. Tofacitinib can be considered as upfront oral therapy after failure of conventional management.","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":"139559195","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":"P264 The utility of ANCA in Ulcerative Colitis and Crohn’s Disease: A Retrospective Cohort Study in Taiwan","authors":"Y H Wu, C P Wang, P J Huang, H C Lai, K S Cheng, J W Chou","doi":"10.1093/ecco-jcc/jjad212.0394","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0394","url":null,"abstract":"Background Inflammatory bowel disease (IBD) includes two chronic idiopathic inflammatory diseases: ulcerative colitis (UC) and Crohn disease (CD). The diagnosis of IBD depends on clinical, endoscopic, histological, radiological and biochemical criteria, which may be invasive, time consuming and usually not accepted by patients with IBD. Antineutrophil cytoplasmic antibodies (ANCAs) is believed to be related to IBD. The aim of this study was to investigate these serological markers and the evidence for their use in the diagnosis and management of IBD in Taiwan. Methods We conducted a retrospective cohort study in adult IBD patients who had received the serum examinations using the medical records of China Medical University Hospital between 1 January 1980 and 31 October. 2023. Results A total of 301 IBD patients (194 with UC, 107 with CD) were included in this current study. A high proportion were male (IBD 70.41%; UC 65.63%, and CD 76.71%). The mean diagnostic age of these enrolled patients was 42.9 years. In our patients, the prevalence of positive anti-HCV Ab is 0.0% in UC patients and 0.96% in CD patients. However, the prevalence of positive HBsAg was 14.5% in UC patients and 9.4% in CD patients. The prevalence of pANCA was 21.2% in UC patients and 1.4% in CD patients, respectively. The prevalence of cANCA was 3.1% in UC patients and 0.0% in CD patients. This pattern of low sensitivity and high specificity for pANCA is also seen in UC patients in various cohort studies. The serum positivity of p-ANCA was significantly higher in UC patients (Figure 1). UC patients with positive p-ANCA were older than CD patients with positive p-ANCA (44.9 vs. 37.3 years). Furthermore, we found that the incidence of positive p-ANCA in UC patients with E1, E2, and E3 at diagnosis was 3.5%, 39.2%, and 57.1%, respectively (Table 1). The serum levels of ANCA-IgG were indeed higher in patients in the severe group than those in the moderate and mild groups. Conclusion Serological biomarkers have been demonstrated to be a series of rapid, non-invasive approaches for assessments of early diagnosis, disease activity and prognosis for IBD. ANCA may be helpful in the early diagnosis of UC and in differentiating it from CD. UC patients with positive ANCA have a higher rate of intestinal mucosal vasculitis than UC patients with negative ANCA. Furthermore, ANCA may also contributes to the pathogenesis of HBV-related systemic vasculitis. Therefore, the management of HBV-related vasculitis includes control the immune complex formation and reaction as well as antiviral agents to reduce the antigenic load resulting in reduction of inflammation. Moreover, effective biomarkers with high sensitivity and specificity need to be investigated in the future.","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":"139559206","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":"P169 Circulating eNAMPT predicts anti-TNF response in IBD patients: possible place in therapy of anti-eNAMPT antibody","authors":"C Travelli, G Cascetta, G colombo, A Alessi, E Caputo, M V Lenti, A Pasini, C Porta, D Ribaldone, L Pastorelli, A Di Sabatino, A Genazzani, G P Caviglia, G Stocco","doi":"10.1093/ecco-jcc/jjad212.0299","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0299","url":null,"abstract":"Background extracellular Nicotinamide phosphoribosyltrasferase (eNAMPT) is a cytokine with paracrine and autocrine effects on different cell types. Importantly, eNAMPT levels are increased in patients suffering of Inflammatory Bowel Diseases (IBD). Biologic drugs have been found effective in many IBD patients; however, a large proportion of patients with severe disease fail to achieve remission due to lack of drug response, loss of response, drug intolerance, or severe side effects that require cessation of therapy. Therefore, there is a clinical need for predictive response biomarkers as well as for new therapeutic strategies. Methods First, we investigated the expression of NAMPT in biopsies, in stools and the secretion of eNAMPT in serum in four cohorts of IBD patients. Second, we investigated if circulating eNAMPT levels correlate with the clinical response to biologics (infliximab, adalimumab, ustekinumab, vedolizumab). Clinical response is defined as a reduction of >2 points in HBI (for CD) and in pMAYO (for UC) from baseline. Third, we have developed a monoclonal anti-eNAMPT antibody and we have evaluated its preclinical efficacy in acute and chronic preclinical models of IBD. Results We have determined the levels of circulating eNAMPT in three cohorts of patients that were not controlled by DMARDs and were treated with infliximab (IFX, cohort 1 and 3) or adalimumab (ADA, cohort 2). Notably, we confirmed a pronounced variability through the cohorts, identifying a group of patients with eNAMPT serum levels comparable with healthy adult populations and a group that showed elevated levels of eNAMPT. Performing a ROC curve analysis, a cutoff of 4.5 ng/ml can be extrapolated to discriminate these two populations. Noteworthy, 100% patients with levels of eNAMPT below 4.5 ng/ml were responsive to infliximab/adalimumab. In contrast, anti-TNF therapy failed either at 14 or 22 weeks in some patients with high circulating levels of eNAMPT, indicating that high systemic eNAMPT might be associated with an increased risk of resistance to anti-TNF therapy. Notably, we found also that eNAMPT levels in stools of IBD patients are elevated compared to healthy subjects. Then, we have developed and validated a candidate monoclonal antibody (called C269) which bind to eNAMPT, block is cytokine activity and reduces IBD symptoms, immune infiltrate and fibrosis in DSS and DNBS models. Conclusion Our data demonstrate that eNAMPT serum levels correlate with the clinical response to anti-TNF therapies suggesting that eNAMPT is not a simple by- stander of IBD, and that local and serum eNAMPT could be define as a biomarker to define the responsiveness to biologics. Notably, its neutralization might be a pharmacological strategy worth investigating.","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":"139559213","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}