Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.0554
B Lee, B Keum, S Kim, H Jeon, Y Jeen, C Hoonjai
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.
{"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":"4 1","pages":""},"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}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.0836
R Banerjee, M Dhanush, N Raghunathan, P Pal, V Joshi, R Patel, S Godbole, Y Akki, S Valluri, P Nagasuri, A Haridas
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.
{"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&lt;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&lt;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":"16 1","pages":""},"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}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.0394
Y H Wu, C P Wang, P J Huang, H C Lai, K S Cheng, J W Chou
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.
{"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":"25 1","pages":""},"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}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.0299
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
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.
{"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 &gt;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":"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":"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}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.1090
L Vuitton, N Mathieu, B D Ye, D H Kim, A L Jeong, Y N Lee, S Schreiber
Background Clinical associations between initial response and long-term outcome are well established for IV IFX in IBD.1,2 In 2020, SC IFX was approved in Europe for treating moderate-to-severe Crohn’s disease (CD) or ulcerative colitis (UC), based on a pivotal randomised trial (NCT02883452) comparing SC and IV IFX.3 This post hoc analysis investigated clinical outcomes in patients (pts) treated with SC or IV IFX, by response to IV IFX induction. Methods In the pivotal trial, adults with active CD or UC received IV IFX induction (5 mg/kg; Week [W] 0 and W2), before randomisation to SC (n=66) or IV (n=65) arms. W6 clinical response (≥70-point decrease in Crohn’s Disease Activity Index [CDAI] score [CD]; ≥2-point decrease in partial Mayo score with ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding subscore of 0 or 1 [UC]) was a stratification factor. The SC arm received SC IFX (120/240 mg for pts weighing <80/≥80 kg) every 2 weeks from W6–54; the IV arm received IV IFX 5 mg/kg every 8 weeks (W6–22), then switched to SC IFX (W30–54). Rates of clinical remission (CDAI score <150 [CD]; partial Mayo score ≤1 [UC]) and trough IFX concentrations (Ctrough) were assessed at W6, W30 and W54. Analyses were descriptive. Results There were 101 induction responders (IRs) to IV IFX, who were randomised to the SC arm (n=49, 74.2%; SC-IR subset) or the IV arm (n=52, 80.0%; IV-IR subset). Correspondingly, there were 17 (25.8%) and 13 (20.0%) induction non-responders (INRs; SC-INR and IV-INR subsets, respectively). In both study arms, IRs had higher clinical remission rates than INRs at both W30 and W54 (Figure A). Comparing by formulation, the SC-INR subset had nearly twice the W30 clinical remission rate of the IV-INR subset (58.8% vs. 30.8%; p=0.159 [Fisher exact test]). In addition, IV-INR subset clinical remission rates numerically increased after pts switched to SC IFX (W30: 30.8% vs. W54: 46.2%; p=0.476 [McNemar test]). These observations were generally consistent with Ctrough findings (Figure B); median Ctrough in the IV-INR subset increased from 1.5 to 18.3 µg/mL (p=0.005 [Wilcoxon signe-drank test]) after switching to SC IFX. Conclusion Findings suggested associations between initial response to IFX induction therapy and positive long-term outcomes for both SC and IV IFX, and supported potential benefits with SC IFX maintenance therapy for INRs, compared with the option of IV IFX maintenance. Given the post hoc nature of the analysis and the small analysis population (thus statistical inconclusiveness), investigation in larger studies is warranted. 1Murthy SK et al. Inflamm Bowel Dis 2015;21:2090–6. 2Wong ECL et al. J Crohns Colitis 2021;15:1114–9. 3Schreiber S et al. Gastroenterology 2021;160:2340–53.
{"title":"P960 Comparison of clinical outcomes by induction therapy response status in patients with Inflammatory Bowel Disease (IBD) treated with subcutaneous (SC) versus intravenous (IV) infliximab (IFX): Post hoc analysis of a pivotal, randomised controlled trial","authors":"L Vuitton, N Mathieu, B D Ye, D H Kim, A L Jeong, Y N Lee, S Schreiber","doi":"10.1093/ecco-jcc/jjad212.1090","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.1090","url":null,"abstract":"Background Clinical associations between initial response and long-term outcome are well established for IV IFX in IBD.1,2 In 2020, SC IFX was approved in Europe for treating moderate-to-severe Crohn’s disease (CD) or ulcerative colitis (UC), based on a pivotal randomised trial (NCT02883452) comparing SC and IV IFX.3 This post hoc analysis investigated clinical outcomes in patients (pts) treated with SC or IV IFX, by response to IV IFX induction. Methods In the pivotal trial, adults with active CD or UC received IV IFX induction (5 mg/kg; Week [W] 0 and W2), before randomisation to SC (n=66) or IV (n=65) arms. W6 clinical response (≥70-point decrease in Crohn’s Disease Activity Index [CDAI] score [CD]; ≥2-point decrease in partial Mayo score with ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding subscore of 0 or 1 [UC]) was a stratification factor. The SC arm received SC IFX (120/240 mg for pts weighing &lt;80/≥80 kg) every 2 weeks from W6–54; the IV arm received IV IFX 5 mg/kg every 8 weeks (W6–22), then switched to SC IFX (W30–54). Rates of clinical remission (CDAI score &lt;150 [CD]; partial Mayo score ≤1 [UC]) and trough IFX concentrations (Ctrough) were assessed at W6, W30 and W54. Analyses were descriptive. Results There were 101 induction responders (IRs) to IV IFX, who were randomised to the SC arm (n=49, 74.2%; SC-IR subset) or the IV arm (n=52, 80.0%; IV-IR subset). Correspondingly, there were 17 (25.8%) and 13 (20.0%) induction non-responders (INRs; SC-INR and IV-INR subsets, respectively). In both study arms, IRs had higher clinical remission rates than INRs at both W30 and W54 (Figure A). Comparing by formulation, the SC-INR subset had nearly twice the W30 clinical remission rate of the IV-INR subset (58.8% vs. 30.8%; p=0.159 [Fisher exact test]). In addition, IV-INR subset clinical remission rates numerically increased after pts switched to SC IFX (W30: 30.8% vs. W54: 46.2%; p=0.476 [McNemar test]). These observations were generally consistent with Ctrough findings (Figure B); median Ctrough in the IV-INR subset increased from 1.5 to 18.3 µg/mL (p=0.005 [Wilcoxon signe-drank test]) after switching to SC IFX. Conclusion Findings suggested associations between initial response to IFX induction therapy and positive long-term outcomes for both SC and IV IFX, and supported potential benefits with SC IFX maintenance therapy for INRs, compared with the option of IV IFX maintenance. Given the post hoc nature of the analysis and the small analysis population (thus statistical inconclusiveness), investigation in larger studies is warranted. 1Murthy SK et al. Inflamm Bowel Dis 2015;21:2090–6. 2Wong ECL et al. J Crohns Colitis 2021;15:1114–9. 3Schreiber S et al. Gastroenterology 2021;160:2340–53.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559255","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}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.0595
N Krugliak Cleveland, N K Choi, J A Klein, E N Fear, Z D Fine, N M Garcia, E A Picker, S R Friedberg, R D Cohen, S R Dalal, J Pekow, D Choi, D T Rubin
Background Upadacitinib (UPA) is a novel selective Janus kinase 1 inhibitor that has shown efficacy and received approval for the treatment of moderate-to-severe ulcerative colitis (UC) and Crohn's disease (CD). We previously reported a large real-world experience of UPA induction in UC and CD (Friedberg, CGH. 2023). Here we report our 1-year real-world experience. Methods This is a prospectively collected study of clinical outcomes of UPA treatment in patients with UC and CD using predetermined intervals at weeks 0, 2, 4, 8, then every 3 months until week 52 as part of a formalized treatment protocol at our institution. We used the Simple Clinical Colitis Activity Index and the Harvey-Bradshaw index, as well as C-reactive protein and faecal calprotectin to assess efficacy, and also recorded treatment-related adverse events and serious adverse events. Results 110 patients were initiated on UPA and followed for a one-year period (CD=57, UC=44, IBDU=5, pouchitis=4). 109/110 (99%) were biologic exposed and 31/110 (28.2 %) were tofacitinib exposed. 99/110 (90%) were initiated on UPA for luminal disease (Table 1). 54 patients remained on UPA therapy at 1 year. In UC: week 8 clinical response and remission was 24/47 (51.1%), 39/47 (83%), respectively; week 26 clinical response and remission was 20/34 (58.8%), 24/34 (70.6%), respectively; 52 week clinical response and remission was 17/30 (56.7%), 29/30 (96.7%), respectively. In CD: week 8 clinical response and remission was 14/32 (43.8%), 25/32 (78.1%%), respectively; week 26 clinical response and remission was 9/22 (40.9%), 15/22 (68.2%), respectively; 52 week clinical response and remission was 10/17 (58.8%), 13/17 (76.5%), respectively. 56 patients discontinued UPA prior to the 1 year follow-up, 13 were due to adverse events[DR1] . The most commonly experienced AEs leading to discontinuation was dermatological side effects (CD=2, UC=2). One instance of shingles occurred leading to discontinuation. No other serious infections or serious adverse events including VTE, MACE, or malignancies occurred. Conclusion In this large 1-year real-world experience in medically resistant patients with UC or CD, we report that UPA is both effective and safe, including in those who had prior exposure to tofacitinib.
{"title":"P465 Upadacitinib is effective and safe for the treatment of ulcerative colitis and Crohn’s disease: 1-year prospective real-world experience","authors":"N Krugliak Cleveland, N K Choi, J A Klein, E N Fear, Z D Fine, N M Garcia, E A Picker, S R Friedberg, R D Cohen, S R Dalal, J Pekow, D Choi, D T Rubin","doi":"10.1093/ecco-jcc/jjad212.0595","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0595","url":null,"abstract":"Background Upadacitinib (UPA) is a novel selective Janus kinase 1 inhibitor that has shown efficacy and received approval for the treatment of moderate-to-severe ulcerative colitis (UC) and Crohn's disease (CD). We previously reported a large real-world experience of UPA induction in UC and CD (Friedberg, CGH. 2023). Here we report our 1-year real-world experience. Methods This is a prospectively collected study of clinical outcomes of UPA treatment in patients with UC and CD using predetermined intervals at weeks 0, 2, 4, 8, then every 3 months until week 52 as part of a formalized treatment protocol at our institution. We used the Simple Clinical Colitis Activity Index and the Harvey-Bradshaw index, as well as C-reactive protein and faecal calprotectin to assess efficacy, and also recorded treatment-related adverse events and serious adverse events. Results 110 patients were initiated on UPA and followed for a one-year period (CD=57, UC=44, IBDU=5, pouchitis=4). 109/110 (99%) were biologic exposed and 31/110 (28.2 %) were tofacitinib exposed. 99/110 (90%) were initiated on UPA for luminal disease (Table 1). 54 patients remained on UPA therapy at 1 year. In UC: week 8 clinical response and remission was 24/47 (51.1%), 39/47 (83%), respectively; week 26 clinical response and remission was 20/34 (58.8%), 24/34 (70.6%), respectively; 52 week clinical response and remission was 17/30 (56.7%), 29/30 (96.7%), respectively. In CD: week 8 clinical response and remission was 14/32 (43.8%), 25/32 (78.1%%), respectively; week 26 clinical response and remission was 9/22 (40.9%), 15/22 (68.2%), respectively; 52 week clinical response and remission was 10/17 (58.8%), 13/17 (76.5%), respectively. 56 patients discontinued UPA prior to the 1 year follow-up, 13 were due to adverse events[DR1] . The most commonly experienced AEs leading to discontinuation was dermatological side effects (CD=2, UC=2). One instance of shingles occurred leading to discontinuation. No other serious infections or serious adverse events including VTE, MACE, or malignancies occurred. Conclusion In this large 1-year real-world experience in medically resistant patients with UC or CD, we report that UPA is both effective and safe, including in those who had prior exposure to tofacitinib.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559269","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}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.0563
N L Avellaneda, G Pellino, A Maroli, A Tottrup, G Bislenghi, J Colpaert, A D'Hoore, L Giorgi, P Juachon, S Harsløf, A de Buck Van Overstraeten, P Olivera, J Gomez, S Holubar, E Lincango Naranjo, S Steele, A Merchea, A Shacker, M Marti Gallostra, M Kraft, P G Kotze, B Yuki Maruyana, S Wexner, Z Garoufalia, C Zhihui, D Hahnloser, D Rrupa, C Buskens, A Haanappel, J Warusavitarne, K Williams, P Christensen, A Spinelli
Background Recent evidence challenges the current standard of offering surgery to patients with ileocecal Crohn’s disease only when they present complications of the disease. Methods A retrospective, multicenter comparative analysis was performed including patients operated for primary ileocecal CD at 12 referral centers. Patients were divided in 2 groups, according to indication of surgery for inflammatory (ICD) or complicated (CCD) phenotype. Short-term results were compared. Patients operated on for primary isolated ileocaecal CD (last 50 cm of the terminal ileum and cecum), either for predominantly inflammatory phenotype or for complications of the disease (stricturing or fistulizing pattern), between January 2012 - December 2021 were considered eligible to participate in this study. Patients with previous abdominal procedures for CD, and patients who had activity of the disease in other intestinal segments other than the ileocaecal region at the time of surgery, were excluded from the study. Results 2013 patients were included, 291 (14.5%) in the ICD group. No differences were found between groups in time from diagnosis to surgery or in the levels of exposure to biologic drugs before indication of surgery. CCD patients had higher rates of low BMI, anemia (40.9 vs. 27%, p: < 0.001), and low albumin (11.3 vs. 2.6%, p: < 0.001). CCD patients had longer operations, lower rates of laparoscopic approach (84.3 vs. 93.1%, p: 0.001), and higher conversion rates (9.3 vs. 1.9%, p: < 0.001). CCD had longer hospital stay and higher postoperative complication rates (26.1 vs. 21.3%, p: 0.083). Anastomotic leakage and reoperations were also more frequent in this group. More patients in the CCD group required an extended bowel resection (14.1 vs. 8.3%, p: 0.017). In multivariate analysis, CCD was associated with prolonged surgeries (OR: 3.44, p: 0.001) and requirements of multiple intraoperative procedures (OR: 8.39, p: 0.030). Conclusion Indication of surgery in patients who present an inflammatory phenotype of CD was associated with better outcomes when compared to patients operated on for complications of the disease, without a difference between groups in time from diagnosis to surgery.
{"title":"P433 Short-term outcomes of surgical treatment in primary ileocecal Crohn’s disease patients. Results of Crohn’s(urg) study, multicenter, retrospective, comparative analysis between indications for luminal and complicated phenotype","authors":"N L Avellaneda, G Pellino, A Maroli, A Tottrup, G Bislenghi, J Colpaert, A D'Hoore, L Giorgi, P Juachon, S Harsløf, A de Buck Van Overstraeten, P Olivera, J Gomez, S Holubar, E Lincango Naranjo, S Steele, A Merchea, A Shacker, M Marti Gallostra, M Kraft, P G Kotze, B Yuki Maruyana, S Wexner, Z Garoufalia, C Zhihui, D Hahnloser, D Rrupa, C Buskens, A Haanappel, J Warusavitarne, K Williams, P Christensen, A Spinelli","doi":"10.1093/ecco-jcc/jjad212.0563","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0563","url":null,"abstract":"Background Recent evidence challenges the current standard of offering surgery to patients with ileocecal Crohn’s disease only when they present complications of the disease. Methods A retrospective, multicenter comparative analysis was performed including patients operated for primary ileocecal CD at 12 referral centers. Patients were divided in 2 groups, according to indication of surgery for inflammatory (ICD) or complicated (CCD) phenotype. Short-term results were compared. Patients operated on for primary isolated ileocaecal CD (last 50 cm of the terminal ileum and cecum), either for predominantly inflammatory phenotype or for complications of the disease (stricturing or fistulizing pattern), between January 2012 - December 2021 were considered eligible to participate in this study. Patients with previous abdominal procedures for CD, and patients who had activity of the disease in other intestinal segments other than the ileocaecal region at the time of surgery, were excluded from the study. Results 2013 patients were included, 291 (14.5%) in the ICD group. No differences were found between groups in time from diagnosis to surgery or in the levels of exposure to biologic drugs before indication of surgery. CCD patients had higher rates of low BMI, anemia (40.9 vs. 27%, p: &lt; 0.001), and low albumin (11.3 vs. 2.6%, p: &lt; 0.001). CCD patients had longer operations, lower rates of laparoscopic approach (84.3 vs. 93.1%, p: 0.001), and higher conversion rates (9.3 vs. 1.9%, p: &lt; 0.001). CCD had longer hospital stay and higher postoperative complication rates (26.1 vs. 21.3%, p: 0.083). Anastomotic leakage and reoperations were also more frequent in this group. More patients in the CCD group required an extended bowel resection (14.1 vs. 8.3%, p: 0.017). In multivariate analysis, CCD was associated with prolonged surgeries (OR: 3.44, p: 0.001) and requirements of multiple intraoperative procedures (OR: 8.39, p: 0.030). Conclusion Indication of surgery in patients who present an inflammatory phenotype of CD was associated with better outcomes when compared to patients operated on for complications of the disease, without a difference between groups in time from diagnosis to surgery.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559381","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}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.0411
M Peng, T Pu, Y Zhao
Background As a non-invasive, accurate, and feasible examination, transabdominal ultrasound（TAUS） is of great value in disease monitoring of ulcerative colitis. The cut-off for disease activity of 3.0 or 4.0 mm is often debated， and studies lacked assessment of treatment response. This study aimed to assess the diagnostic accuracy of TAUS in detecting disease activity in adult patients with UC using endoscopy as the reference standard and evaluate TAUS for treatment response in a longitudinal cohort. Methods This study prospectively consecutive adult patients with an established diagnosis of UC in the First Affiliated Hospital of Zhengzhou University between June 2022 and September 2023. The patients with moderate-to-severe disease activity at baseline should have follow-up endoscopic assessment after induction, with available corresponding TAUS. The primary outcome of this study was the difference in BWT in the descending colon(DC) or sigmoid colon(SC) for patients with and without segmental endoscopic response after treatment. Endoscopic remission was defined as MES=0-1 or UCEIS=0-1, and Endoscopic response as a decrease of MES ≥1 or a reduction of UCEIS ≥2. Results A total of 315 colon segments in 80 patients were included. 171 (54.3%) colorectal segments had endoscopic remission and 144(45.7%) were in endoscopic activity. The TAUS parameters correlated with the Mayo endoscopic sub-score with significant differences between patients in endoscopic remission and patients in endoscopic activity. And we found 3.45mm(AUROC 0.833;95%CI 0.789-0.878， P＜0.001) to be the cutoff for endoscopic remission with 78% sensitivity and 75% specificity. The multivariable analysis identified BWT， the Colour Doppler Signal(CDS), and the wall layer stratification as independent predictors for endoscopic activity（ P＜0.001、=0.004、=0.001）. BWT in the DC or SC was significantly lower in patients with endoscopic response than those without after treatment. A 28% decrease in BWT from baseline predicted endoscopic response [AUROC 0.743;95%CI 0.589-0.896， P=0.015] with 58% sensitivity and 93% specificity. Multivariable analysis among all the ultrasound parameters considered normal wall layer stratification at baseline as the only independent predictor of endoscopic response at reassessment (odds ratio [OR]23.334, 95% CI 2.257-241.219; p = 0.008). Conclusion TAUS, importantly BWT, CDS, and wall layer stratification as the crucial parameters, is highly accurate in detecting disease activity and treatment response when evaluated against endoscopic outcomes. Normal intestinal wall stratification at baseline predicts long-term endoscopic response.
{"title":"P281 The role of transabdominal ultrasound in evaluating Ulcerative Colitis disease activity and predicting treatment response","authors":"M Peng, T Pu, Y Zhao","doi":"10.1093/ecco-jcc/jjad212.0411","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0411","url":null,"abstract":"Background As a non-invasive, accurate, and feasible examination, transabdominal ultrasound（TAUS） is of great value in disease monitoring of ulcerative colitis. The cut-off for disease activity of 3.0 or 4.0 mm is often debated， and studies lacked assessment of treatment response. This study aimed to assess the diagnostic accuracy of TAUS in detecting disease activity in adult patients with UC using endoscopy as the reference standard and evaluate TAUS for treatment response in a longitudinal cohort. Methods This study prospectively consecutive adult patients with an established diagnosis of UC in the First Affiliated Hospital of Zhengzhou University between June 2022 and September 2023. The patients with moderate-to-severe disease activity at baseline should have follow-up endoscopic assessment after induction, with available corresponding TAUS. The primary outcome of this study was the difference in BWT in the descending colon(DC) or sigmoid colon(SC) for patients with and without segmental endoscopic response after treatment. Endoscopic remission was defined as MES=0-1 or UCEIS=0-1, and Endoscopic response as a decrease of MES ≥1 or a reduction of UCEIS ≥2. Results A total of 315 colon segments in 80 patients were included. 171 (54.3%) colorectal segments had endoscopic remission and 144(45.7%) were in endoscopic activity. The TAUS parameters correlated with the Mayo endoscopic sub-score with significant differences between patients in endoscopic remission and patients in endoscopic activity. And we found 3.45mm(AUROC 0.833;95%CI 0.789-0.878， P＜0.001) to be the cutoff for endoscopic remission with 78% sensitivity and 75% specificity. The multivariable analysis identified BWT， the Colour Doppler Signal(CDS), and the wall layer stratification as independent predictors for endoscopic activity（ P＜0.001、=0.004、=0.001）. BWT in the DC or SC was significantly lower in patients with endoscopic response than those without after treatment. A 28% decrease in BWT from baseline predicted endoscopic response [AUROC 0.743;95%CI 0.589-0.896， P=0.015] with 58% sensitivity and 93% specificity. Multivariable analysis among all the ultrasound parameters considered normal wall layer stratification at baseline as the only independent predictor of endoscopic response at reassessment (odds ratio [OR]23.334, 95% CI 2.257-241.219; p = 0.008). Conclusion TAUS, importantly BWT, CDS, and wall layer stratification as the crucial parameters, is highly accurate in detecting disease activity and treatment response when evaluated against endoscopic outcomes. Normal intestinal wall stratification at baseline predicts long-term endoscopic response.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559392","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}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.1359
S Shin Shin, Y J Cho, J Yang, H K Kim, P Rintarhat, M Park, K Lagree, D M Underhill, C S Yang, J M Moon, J Seo, K Kim, W H Jung, C H Choi
Background Accumulating evidence has underscored the role of gut fungal microbiota (mycobiota) in the development of inflammatory bowel disease. We aimed to isolate a Malassezia strain directly from the human intestine mucosal surface from the patients with ulcerative colitis (UC) and investigated its genome and virulence in comparison with the same fungal species isolated from the human skin. Methods Mucosal lavage samples were collected separately from colonic areas with and without inflammation in patients with UC. Samples from healthy individuals (HT) were obtained in the same manner as from patients with UC at sigmoid or descending colon. Skin samples were taken from HT in our previous work. DNA was extracted from these lavage samples, and fungal isolation was conducted using PCR amplification with ITS4 and ITS5 primers. Comprehensive analysis and comparison of the genomes, transcriptomes, and virulence between M. globosa gut isolates and those of M. globosa strains isolated from the skin were performed. To determine the contribution of M. globosa gut isolates to exacerbating inflammation, 1107 fungal cells were orally gavaged to DSS-induced colitis mouse model for three days. Results Total 56 and 11 intestinal water-lavage samples from 29 UC patients and 11 HT were obtained respectively. The α- and b-diversities of mycobiota showed no significant differences between the groups, patients with UC vs. HT or the sites with inflammation vs. non-inflammation of the patient with UC. Malassezia was the fifth most frequently found fungal genus throughout the samples, and live fungal strains belong to 28 and 7 different species were isolated from the patients with UC and HT, respectively. The patients with UC tend to have higher frequency of M. globosa and M. restricta than HT in their gut mucosal surface with inflammation. Whole genome sequencing showed no specific genomic characteristics between gut-isolated M. globosa and skin-isolated M. globosa. However, gut-isolated M. globosa were suffered more from the higher oxygen levels than the skin isolates in different oxygen concentrations. In a mouse model, gut-isolated M. globosa exhibited a more pronounced exacerbation of DSS-induced colitis and elevated production of inflammatory cytokines, including TNF-a, IL-6, IL-12p40, IL-1b, and IL-18, while the skin isolates showed no difference compared to the negative control (Figure). Conclusion Our data shed new light on the pivotal role of M. globosa in the pathogenesis of UC, highlighting the potential influence of niche-specific adaptations on the virulence of this fungus. These findings provide critical insights into the complex interplay between the member of the gut mycobiota and host health.
{"title":"P1229 The Role and Niche-Specific Adaptation of Malassezia in patients with Ulcerative colitis","authors":"S Shin Shin, Y J Cho, J Yang, H K Kim, P Rintarhat, M Park, K Lagree, D M Underhill, C S Yang, J M Moon, J Seo, K Kim, W H Jung, C H Choi","doi":"10.1093/ecco-jcc/jjad212.1359","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.1359","url":null,"abstract":"Background Accumulating evidence has underscored the role of gut fungal microbiota (mycobiota) in the development of inflammatory bowel disease. We aimed to isolate a Malassezia strain directly from the human intestine mucosal surface from the patients with ulcerative colitis (UC) and investigated its genome and virulence in comparison with the same fungal species isolated from the human skin. Methods Mucosal lavage samples were collected separately from colonic areas with and without inflammation in patients with UC. Samples from healthy individuals (HT) were obtained in the same manner as from patients with UC at sigmoid or descending colon. Skin samples were taken from HT in our previous work. DNA was extracted from these lavage samples, and fungal isolation was conducted using PCR amplification with ITS4 and ITS5 primers. Comprehensive analysis and comparison of the genomes, transcriptomes, and virulence between M. globosa gut isolates and those of M. globosa strains isolated from the skin were performed. To determine the contribution of M. globosa gut isolates to exacerbating inflammation, 1107 fungal cells were orally gavaged to DSS-induced colitis mouse model for three days. Results Total 56 and 11 intestinal water-lavage samples from 29 UC patients and 11 HT were obtained respectively. The α- and b-diversities of mycobiota showed no significant differences between the groups, patients with UC vs. HT or the sites with inflammation vs. non-inflammation of the patient with UC. Malassezia was the fifth most frequently found fungal genus throughout the samples, and live fungal strains belong to 28 and 7 different species were isolated from the patients with UC and HT, respectively. The patients with UC tend to have higher frequency of M. globosa and M. restricta than HT in their gut mucosal surface with inflammation. Whole genome sequencing showed no specific genomic characteristics between gut-isolated M. globosa and skin-isolated M. globosa. However, gut-isolated M. globosa were suffered more from the higher oxygen levels than the skin isolates in different oxygen concentrations. In a mouse model, gut-isolated M. globosa exhibited a more pronounced exacerbation of DSS-induced colitis and elevated production of inflammatory cytokines, including TNF-a, IL-6, IL-12p40, IL-1b, and IL-18, while the skin isolates showed no difference compared to the negative control (Figure). Conclusion Our data shed new light on the pivotal role of M. globosa in the pathogenesis of UC, highlighting the potential influence of niche-specific adaptations on the virulence of this fungus. These findings provide critical insights into the complex interplay between the member of the gut mycobiota and host health.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559402","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}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.1381
M van Gaalen, M van Pieterson, L de Ridder, L Derikx, J Escher
Background Transition programs are designed to prepare adolescent patients with inflammatory bowel disease (IBD) for their new role in adult care. The outcome of these programs is often assessed in a qualitative way (patient satisfaction, quality of life, disease burden). However, there is no quantitative measure to evaluate the effect of a transition program. The aim of this study was to develop and validate a Transition Success Score (TSS) by the identified key components of successful transition. Methods The TSS was developed through an international Delphi consensus study, with the expert panel of pediatric and adult healthcare providers and patients. The top 10 key outcome items associated with success of transition were collated into one questionnaire. In every round, the minimum response rate required was 80%, and a consensus of more than 80% was necessary for each item. After four rounds of discussion, a consensus was reached on the initial version of the TSS. This score included seven items for adult healthcare providers to evaluate the patient's disease management behavior, including shared decision making, therapy adherence, and appointment attendance. Additionally, two items concern patient and parent experience concerning the transition period. The TSS was subsequently employed and validated in a prospective multicenter cohort of young adult IBD patients, who made the transfer 9-15 months ago, in the Netherlands. Results In seven hospitals, 160 IBD patients (median age 19.05, male 48.8%, Crohn's disease 56%, median age at diagnose 13.97) completed the TSS, at 9-15 months after transfer to adult care. Hypothesis testing for construct validation revealed significant association of characteristics related to transition care such as knowledge (RTT), independence (TRAQ), and quality of life (IBDQ) (p=<0.005). In addition, Rasch analysis for structural validation showed that the TSS was discriminating at lower levels of transition success (Figure 1). Internal consistency, as measured by Cronbach alpha, was acceptable at 0.64. TSS was significantly lower in patients with high disease burden, exacerbation within the first year after transfer and parental dependency. Also, TSS was lower in certain patient profile types, characterized as either "laid back, nonchalant" or "worried and uncertain". Conclusion The Transition Success Score (TSS) can serve as a quantitative measure to help identify IBD patients who did not have successful transition to adult care. TSS can be utilized for identifying factors that impact successful transition and for measuring the effect of various transition programs in IBD.
{"title":"N09 Transition Success Score as a valid quantitative measure to evaluate the effect of transitional care in IBD patients","authors":"M van Gaalen, M van Pieterson, L de Ridder, L Derikx, J Escher","doi":"10.1093/ecco-jcc/jjad212.1381","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.1381","url":null,"abstract":"Background Transition programs are designed to prepare adolescent patients with inflammatory bowel disease (IBD) for their new role in adult care. The outcome of these programs is often assessed in a qualitative way (patient satisfaction, quality of life, disease burden). However, there is no quantitative measure to evaluate the effect of a transition program. The aim of this study was to develop and validate a Transition Success Score (TSS) by the identified key components of successful transition. Methods The TSS was developed through an international Delphi consensus study, with the expert panel of pediatric and adult healthcare providers and patients. The top 10 key outcome items associated with success of transition were collated into one questionnaire. In every round, the minimum response rate required was 80%, and a consensus of more than 80% was necessary for each item. After four rounds of discussion, a consensus was reached on the initial version of the TSS. This score included seven items for adult healthcare providers to evaluate the patient's disease management behavior, including shared decision making, therapy adherence, and appointment attendance. Additionally, two items concern patient and parent experience concerning the transition period. The TSS was subsequently employed and validated in a prospective multicenter cohort of young adult IBD patients, who made the transfer 9-15 months ago, in the Netherlands. Results In seven hospitals, 160 IBD patients (median age 19.05, male 48.8%, Crohn's disease 56%, median age at diagnose 13.97) completed the TSS, at 9-15 months after transfer to adult care. Hypothesis testing for construct validation revealed significant association of characteristics related to transition care such as knowledge (RTT), independence (TRAQ), and quality of life (IBDQ) (p=&lt;0.005). In addition, Rasch analysis for structural validation showed that the TSS was discriminating at lower levels of transition success (Figure 1). Internal consistency, as measured by Cronbach alpha, was acceptable at 0.64. TSS was significantly lower in patients with high disease burden, exacerbation within the first year after transfer and parental dependency. Also, TSS was lower in certain patient profile types, characterized as either \"laid back, nonchalant\" or \"worried and uncertain\". Conclusion The Transition Success Score (TSS) can serve as a quantitative measure to help identify IBD patients who did not have successful transition to adult care. TSS can be utilized for identifying factors that impact successful transition and for measuring the effect of various transition programs in IBD.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"57 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559406","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}
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