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":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":"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":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":"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":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":"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":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":"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":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":"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":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":"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}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.0007
S Balarajah, L Martinez-Gili, J Alexander, B Mullish, R Perry, J Li, J Marchesi, M Parkes, T Orchard, L Hicks, H Williams
Background The current evidence suggests ethnic distinctions in IBD phenotype, and differences in the provision of treatment have been reported. This multi-centre cohort study utilised the UK IBD BioResource dataset to evaluate phenotypic differences between South Asian (SA) and White (WH) IBD, and to explore if these were associated with differences in treatment. Methods Phenotypic and outcome data were extracted from the IBD BioResource. Chi2 (categorical data) and Mann-Whitney U (continuous data) tests were used. Propensity score matching (PSM) accounted for age at diagnosis, sex, smoking status, disease location and behaviour and perianal disease (CD). Differences in medication use (multivariable logistic regression) and surgical outcomes (Kaplan-Meier and Cox regression analysis) were assessed in propensity-matched (PM) cohorts. Results 33,157 (31,932 WH; 1225 SA) individuals were included (48.1% CD, 45.4% UC, 6.5% IBD-U). UC was the predominant disease subtype in SA (UC, SA 57.3% vs WH 44.9%, p<0.001). SA were younger at diagnosis [CD, SA 24 (IQR 17-36) vs WH 26 (IQR 19-39) years, p<0.001; UC, SA 29 (IQR 22-38) vs WH 35 (25-48) years, p<0.001]. SA CD had less ileal disease (SA 30.3% vs WH 38.4%, padj=0.008), and more perianal involvement (SA 38.5% vs WH 32.3%, p=0.009) than WH. SA CD had less stricturing disease (SA 16.9% vs WH 25.6%, padj<0.001). SA UC were more likely to have extensive disease (SA 41.7% vs WH 34.1%, padj<0.001). Initial analyses in non-PSM cohorts showed that fewer SA CD underwent surgery [SA (n=157,37.4%) vs WH (n=7532,50.4%), p<0.001], and that similar proportions of SA (n=33,5.1%) and WH (n=747,5.5%; p=0.15) UC underwent a colectomy. PSM was used to match 355 SA to 355 WH in CD, and 525 SA to 525 WH in UC. Variables were well-balanced. There were no differences in 5-ASA, corticosteroid, thiopurine, anti-TNF or Vedolizumab use (Table 1). In CD, 126 (36.5%) SA and 152 (44.7%) had surgery. Survival analysis in CD showed no difference in the time to surgery (Fig 1A, log-rank 0.28). SA ethnicity was not associated with increased risk of surgery in CD (HR 0.82, 95% CI 0.63-1.07, p=0.14). In UC, 25 (4.8%) and 37 (7.1%) WH had a colectomy. There was no significant difference in the time to colectomy (Fig 1B, log-rank 0.12) nor was SA ethnicity associated with an increased risk of having a colectomy (HR 0.65, 95% CI 0.39-1.11, p=0.12). Conclusion In the largest analysis of SA IBD to date, we have demonstrated phenotypic differences associated with ethnicity. Accounting for these variations, we have shown comparable provision of medical and surgical treatment in SA and WH. These findings indicate consistent care of IBD patients from different ethnic backgrounds in the UK.
背景 目前的证据表明，IBD 的表型存在种族差异，在提供治疗方面也存在差异。这项多中心队列研究利用英国 IBD 生物资源数据集来评估南亚（SA）和白人（WH）IBD 的表型差异，并探讨这些差异是否与治疗差异有关。方法 从 IBD 生物资源中提取表型和结果数据。采用Chi2（分类数据）和Mann-Whitney U（连续数据）检验。倾向评分匹配（PSM）考虑了诊断时的年龄、性别、吸烟状况、患病部位和行为以及肛周疾病（CD）。在倾向匹配（PM）队列中评估了药物使用（多变量逻辑回归）和手术结果（Kaplan-Meier 和 Cox 回归分析）的差异。结果 共纳入 33157 例（31932 例 WH；1225 例 SA）患者（48.1% CD、45.4% UC、6.5% IBD-U）。UC是SA的主要疾病亚型（UC，SA 57.3% vs WH 44.9%，p<0.001）。南澳大利亚人确诊时更年轻[CD，南澳大利亚人 24（IQR 17-36）岁 vs WH 26（IQR 19-39）岁，p<0.001；UC，南澳大利亚人 29（IQR 22-38）岁 vs WH 35（25-48）岁，p<0.001]。与 WH 相比，SA CD 的回肠病变较少（SA 30.3% vs WH 38.4%，p<0.008），肛周受累较多（SA 38.5% vs WH 32.3%，p<0.009）。南澳大利亚州的 CD 病变较少（南澳大利亚州 16.9% vs WH 25.6%，padj<0.001）。SA UC 更有可能患有广泛性疾病（SA 41.7% vs WH 34.1%，padj<0.001）。对非PSM队列的初步分析表明，接受手术的SA CD较少[SA（n=157,37.4%） vs WH（n=75322,50.4%），p<0.001]，接受结肠切除术的SA（n=33,5.1%）和WH（n=747,5.5%；p=0.15）UC比例相似。使用 PSM 将 CD 中的 355 名 SA 与 355 名 WH 匹配，将 UC 中的 525 名 SA 与 525 名 WH 匹配。变量非常均衡。5-ASA、皮质类固醇、硫嘌呤、抗肿瘤坏死因子或维多珠单抗的使用没有差异（表 1）。在 CD 患者中，126 人（36.5%）接受了手术治疗，152 人（44.7%）接受了手术治疗。CD 患者的生存分析表明，手术时间没有差异（图 1A，log-rank 0.28）。在 CD 中，SA 族与手术风险增加无关（HR 0.82，95% CI 0.63-1.07，P=0.14）。在 UC 中，分别有 25 人（4.8%）和 37 人（7.1%）进行了结肠切除术。结肠切除术的时间没有明显差异（图 1B，log-rank 0.12），SA 族也与结肠切除术风险增加无关（HR 0.65，95% CI 0.39-1.11，p=0.12）。结论 在迄今为止最大规模的南澳大利亚 IBD 分析中，我们证实了与种族有关的表型差异。考虑到这些差异，我们发现南澳大利亚州和西澳大利亚州提供的内科和外科治疗具有可比性。这些研究结果表明，英国对不同种族背景的 IBD 患者提供了一致的治疗。
{"title":"OP07 Consistent IBD treatment approaches across South Asian and White ethnicities despite phenotypic variations: a study of 33,157 patients using the IBD BioResource","authors":"S Balarajah, L Martinez-Gili, J Alexander, B Mullish, R Perry, J Li, J Marchesi, M Parkes, T Orchard, L Hicks, H Williams","doi":"10.1093/ecco-jcc/jjad212.0007","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0007","url":null,"abstract":"Background The current evidence suggests ethnic distinctions in IBD phenotype, and differences in the provision of treatment have been reported. This multi-centre cohort study utilised the UK IBD BioResource dataset to evaluate phenotypic differences between South Asian (SA) and White (WH) IBD, and to explore if these were associated with differences in treatment. Methods Phenotypic and outcome data were extracted from the IBD BioResource. Chi2 (categorical data) and Mann-Whitney U (continuous data) tests were used. Propensity score matching (PSM) accounted for age at diagnosis, sex, smoking status, disease location and behaviour and perianal disease (CD). Differences in medication use (multivariable logistic regression) and surgical outcomes (Kaplan-Meier and Cox regression analysis) were assessed in propensity-matched (PM) cohorts. Results 33,157 (31,932 WH; 1225 SA) individuals were included (48.1% CD, 45.4% UC, 6.5% IBD-U). UC was the predominant disease subtype in SA (UC, SA 57.3% vs WH 44.9%, p&lt;0.001). SA were younger at diagnosis [CD, SA 24 (IQR 17-36) vs WH 26 (IQR 19-39) years, p&lt;0.001; UC, SA 29 (IQR 22-38) vs WH 35 (25-48) years, p&lt;0.001]. SA CD had less ileal disease (SA 30.3% vs WH 38.4%, padj=0.008), and more perianal involvement (SA 38.5% vs WH 32.3%, p=0.009) than WH. SA CD had less stricturing disease (SA 16.9% vs WH 25.6%, padj&lt;0.001). SA UC were more likely to have extensive disease (SA 41.7% vs WH 34.1%, padj&lt;0.001). Initial analyses in non-PSM cohorts showed that fewer SA CD underwent surgery [SA (n=157,37.4%) vs WH (n=7532,50.4%), p&lt;0.001], and that similar proportions of SA (n=33,5.1%) and WH (n=747,5.5%; p=0.15) UC underwent a colectomy. PSM was used to match 355 SA to 355 WH in CD, and 525 SA to 525 WH in UC. Variables were well-balanced. There were no differences in 5-ASA, corticosteroid, thiopurine, anti-TNF or Vedolizumab use (Table 1). In CD, 126 (36.5%) SA and 152 (44.7%) had surgery. Survival analysis in CD showed no difference in the time to surgery (Fig 1A, log-rank 0.28). SA ethnicity was not associated with increased risk of surgery in CD (HR 0.82, 95% CI 0.63-1.07, p=0.14). In UC, 25 (4.8%) and 37 (7.1%) WH had a colectomy. There was no significant difference in the time to colectomy (Fig 1B, log-rank 0.12) nor was SA ethnicity associated with an increased risk of having a colectomy (HR 0.65, 95% CI 0.39-1.11, p=0.12). Conclusion In the largest analysis of SA IBD to date, we have demonstrated phenotypic differences associated with ethnicity. Accounting for these variations, we have shown comparable provision of medical and surgical treatment in SA and WH. These findings indicate consistent care of IBD patients from different ethnic backgrounds in the UK.","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":"139559191","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/jjad212.0548
C Minsart, L Toris, C Husson, D Franchimont, C Liefferinckx
Background Current biomarkers of inflammatory bowel disease (IBD) monitoring (serum C-reactive protein (CRP) and faecal calprotectin (FC)) have limitations in terms of specificity (SP) and sensitivity (SE), especially for Crohn’s disease (CD) patients. Lipopolysaccharide-binding protein (LBP) is a soluble acute-phase protein and is thought to partly reflect intestinal permeability by binding to bacterial lipopolysaccharides. The search for new biomarkers to monitor disease activity would improve the management of IBD patients. Methods This is a retrospective study including 69 IBD patients (43 CD and 26 ulcerative colitis (UC)) and 21 healthy controls (HC). Serum LBP levels were measured by enzyme-linked immunosorbent assay. Clinical, biological and endoscopic parameters were analysed for IBD patients. Statistical tests, including nonparametric tests and receiver operating characteristic (ROC) curve analysis, were used to evaluate the diagnostic accuracy of LBP. Results Demographics and baseline data of the overall cohort is presented in Table 1. IBD patients displayed a significantly higher LBP median (29.6 µg/mL [19.8-38.8] in CD and 22.8 [13.7-38.8] in UC) than HC (5.5 [4.4-6.5], P < 0.001) with no overlapping distributions, a finding supported by an AUC of 0.997 and 0.989, respectively for CD and UC patients (Figures 1A). In CD patients, LBP levels gradually increased with endoscopic severity, demonstrating a 1.7-fold rise in active patients compared to remitter patients (P=0.02) (Figure 1B). LBP levels were higher in Montreal B1 compared to B2 and B3 CD patients (P < 0.001) (Figure 1C). Overall, a robust correlation was observed between LBP and CRP (ρ=0.75, P < 0.001). The correlation increased upon the exclusion of cases with normal CRP levels but active endoscopic disease (ρ=0.79, P < 0.001). In those endoscopically active patients with normal CRP, LBP level was higher than in remitter patients (34.3 [29.4-37.6] vs 19.1 [10-24.7], P=0.01) with a discriminative cut-off of 25 µg/mL (SE of 100%, SP of 89%). Likewise, LBP level exhibited a positive correlation with FC (ρ=0.42, P < 0.01) which was further strengthened after excluding cases where FC measurements did not align with endoscopic activity (ρ=0.53, P < 0.01). The median LBP for those patients was 25.6 [18.5-31.5], reflecting again the interest of LBP measurement to evaluate CD activity when FC lacks sensibility. Conclusion Our study suggests that LBP might be a promising non-invasive biomarker for monitoring disease activity, especially in CD patients. Furthermore, in clinical situations where current biomarkers (CRP and FC) lack sensitivity for assessing disease activity, LBP could be discriminative and help filling the gap for reliable therapeutic decisions.
背景 目前监测炎症性肠病（IBD）的生物标记物（血清C反应蛋白（CRP）和粪便钙蛋白（FC））在特异性（SP）和敏感性（SE）方面存在局限性，尤其是对克罗恩病（CD）患者而言。脂多糖结合蛋白（LBP）是一种可溶性急性期蛋白，被认为可通过与细菌脂多糖结合而部分反映肠道通透性。寻找新的生物标记物来监测疾病活动将改善对 IBD 患者的管理。方法 这是一项回顾性研究，包括 69 名 IBD 患者（43 名 CD 患者和 26 名溃疡性结肠炎（UC）患者）和 21 名健康对照组（HC）。血清枸杞多糖水平通过酶联免疫吸附试验测定。对 IBD 患者的临床、生物和内窥镜参数进行了分析。统计检验包括非参数检验和接收者操作特征曲线分析，用于评估枸杞多糖的诊断准确性。结果 表 1 列出了总体队列的人口统计学和基线数据。IBD 患者的枸杞多糖中位数（CD 患者为 29.6 µg/mL [19.8-38.8]，UC 患者为 22.8 [13.7-38.8]）明显高于 HC 患者（5.5 [4.4-6.5]，P< 0.001），且没有重叠分布，CD 和 UC 患者的 AUC 分别为 0.997 和 0.989（图 1A）。在 CD 患者中，枸杞多糖水平随内镜严重程度逐渐升高，活动期患者的枸杞多糖水平是缓解期患者的 1.7 倍（P=0.02）（图 1B）。与 B2 和 B3 CD 患者相比，蒙特利尔 B1 患者的枸杞多糖水平更高（P < 0.001）（图 1C）。总体而言，LBP 与 CRP 之间存在很强的相关性（ρ=0.75，P < 0.001）。在排除 CRP 水平正常但内镜疾病活跃的病例后，相关性增加（ρ=0.79，P < 0.001）。在 CRP 正常的内镜活动期患者中，枸杞多糖水平高于缓解期患者（34.3 [29.4-37.6] vs 19.1 [10-24.7]，P=0.01），分辨临界值为 25 µg/mL（SE 为 100%，SP 为 89%）。同样，枸杞多糖水平与 FC 呈正相关（ρ=0.42，P< 0.01），在排除 FC 测量与内镜活动不一致的病例后，这种相关性进一步加强（ρ=0.53，P< 0.01）。这些患者的 LBP 中位数为 25.6 [18.5-31.5]，再次反映了当 FC 缺乏敏感性时，用 LBP 测量来评估 CD 活动的意义。结论 我们的研究表明，枸杞苷可能是一种很有前景的监测疾病活动的非侵入性生物标志物，尤其是在 CD 患者中。此外，在目前的生物标志物（CRP 和 FC）对评估疾病活动性缺乏敏感性的临床情况下，枸杞多糖可以起到鉴别作用，有助于填补空白，做出可靠的治疗决定。
{"title":"P418 Lipopolysaccharide-Binding Protein (LBP) in Crohn's Disease (CD) Patients: A Promising Non-Invasive Biomarker Monitoring Disease Activity","authors":"C Minsart, L Toris, C Husson, D Franchimont, C Liefferinckx","doi":"10.1093/ecco-jcc/jjad212.0548","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0548","url":null,"abstract":"Background Current biomarkers of inflammatory bowel disease (IBD) monitoring (serum C-reactive protein (CRP) and faecal calprotectin (FC)) have limitations in terms of specificity (SP) and sensitivity (SE), especially for Crohn’s disease (CD) patients. Lipopolysaccharide-binding protein (LBP) is a soluble acute-phase protein and is thought to partly reflect intestinal permeability by binding to bacterial lipopolysaccharides. The search for new biomarkers to monitor disease activity would improve the management of IBD patients. Methods This is a retrospective study including 69 IBD patients (43 CD and 26 ulcerative colitis (UC)) and 21 healthy controls (HC). Serum LBP levels were measured by enzyme-linked immunosorbent assay. Clinical, biological and endoscopic parameters were analysed for IBD patients. Statistical tests, including nonparametric tests and receiver operating characteristic (ROC) curve analysis, were used to evaluate the diagnostic accuracy of LBP. Results Demographics and baseline data of the overall cohort is presented in Table 1. IBD patients displayed a significantly higher LBP median (29.6 µg/mL [19.8-38.8] in CD and 22.8 [13.7-38.8] in UC) than HC (5.5 [4.4-6.5], P &lt; 0.001) with no overlapping distributions, a finding supported by an AUC of 0.997 and 0.989, respectively for CD and UC patients (Figures 1A). In CD patients, LBP levels gradually increased with endoscopic severity, demonstrating a 1.7-fold rise in active patients compared to remitter patients (P=0.02) (Figure 1B). LBP levels were higher in Montreal B1 compared to B2 and B3 CD patients (P &lt; 0.001) (Figure 1C). Overall, a robust correlation was observed between LBP and CRP (ρ=0.75, P &lt; 0.001). The correlation increased upon the exclusion of cases with normal CRP levels but active endoscopic disease (ρ=0.79, P &lt; 0.001). In those endoscopically active patients with normal CRP, LBP level was higher than in remitter patients (34.3 [29.4-37.6] vs 19.1 [10-24.7], P=0.01) with a discriminative cut-off of 25 µg/mL (SE of 100%, SP of 89%). Likewise, LBP level exhibited a positive correlation with FC (ρ=0.42, P &lt; 0.01) which was further strengthened after excluding cases where FC measurements did not align with endoscopic activity (ρ=0.53, P &lt; 0.01). The median LBP for those patients was 25.6 [18.5-31.5], reflecting again the interest of LBP measurement to evaluate CD activity when FC lacks sensibility. Conclusion Our study suggests that LBP might be a promising non-invasive biomarker for monitoring disease activity, especially in CD patients. Furthermore, in clinical situations where current biomarkers (CRP and FC) lack sensitivity for assessing disease activity, LBP could be discriminative and help filling the gap for reliable therapeutic decisions.","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":"139559197","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/jjad212.1035
S Zeissig, R Schmelz, U Helwig, A R Moschen, T Greuter, I Fischer, L Hammer, S Rath, T Kucharzik, C Maaser
Background Upadacitinib (UPA) is an oral, reversible and selective Januskinase-inhibitor (JAKi) that was approved for the treatment of several immune-mediated inflammatory diseases, including moderate to severe ulcerative colitis (UC) (1). While the efficacy of UPA has been demonstrated in clinical trials in UC, real-word (RW) evidence on the effectiveness and safety of UPA in UC remains scarce (2). Here, we shed light on the clinical and sonographic results after 2 and 8 weeks of UPA induction in a large, multinational RW cohort of UC patients. Methods EUROPE is an ongoing, prospective, non-interventional, multi-country study in patients with active UC who initiate therapy with UPA. The study assesses the early clinical effectiveness and the predictive value of early disease improvements including sonographic parameters for the long-term outcome after 52 and 104 weeks. For this interim analysis, we report clinical and sonographic results at baseline (BL), week 2 (2W) and week 8 (8W) of 124 UC patients with a visit after 8W until August 2023. For 75 patients, sonographic BL data for the most affected bowel segment was available. Results Of the 124 UC patients, most were male (60.5%, n = 75) with a median age and disease duration of 37.5 years (27.5 – 50.9) and 6.58 years (2.40–12.13). Almost half of all patients had a pancolitis (48.4%, n = 60) The vast majority of patients was bio-experienced (85.5%, n = 106), a third had been exposed to ≥ 3 biologicals (28.2%, n = 35). At BL, patients had a median bowel wall thickness (BWT) of 5.0 mm (3.8-7.0) in the sigmoid colon. It was the most affected segment in 44.4% of patients (n = 55). Disease activity per paMayo score was 3.0 (2.0-5.0) points, with 72.6% (n = 90) and 38.8% (n = 48) of patients reporting ≥ 3 more stools than usual/day and blood in most stools or bleeding without stool, respectively. At 2W after UPA induction, stool frequency and rectal bleeding substantially improved as reflected by the rate of patients in symptomatic remission significantly increasing from 16.9% (n = 21) at BL to 43.5% (n = 54) at 2W and to 64.5% (n = 80) at W8 (both p < 0.001 vs. BL, fig.1). BWT was reduced significantly as early as 2W (n = 48; p < 0.001) and was ≤ 3mm in more than half of all patients. Considering the overall population, 156 patients were included in the safety analysis. Of these, 23.7% (n = 37) experienced an adverse event of which most were non-serious. Conclusion In this first interim analysis of the EUROPE study, UPA treatment in UC was associated with early clinical and sonographic improvement, with most patients achieving symptomatic remission and/or normalization of BWT by week 8 of treatment. 1-SmPC Upadacitinib 2-Danese, Vermeire et al. Lancet. 2022 Jun 4;399(10341):2113-2128
{"title":"P905 Symptomatic remission and IUS improvements in a multi-national real-world cohort of UC patients treated with Upadacitinib - First results from the IBD-DACH study EUROPE","authors":"S Zeissig, R Schmelz, U Helwig, A R Moschen, T Greuter, I Fischer, L Hammer, S Rath, T Kucharzik, C Maaser","doi":"10.1093/ecco-jcc/jjad212.1035","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.1035","url":null,"abstract":"Background Upadacitinib (UPA) is an oral, reversible and selective Januskinase-inhibitor (JAKi) that was approved for the treatment of several immune-mediated inflammatory diseases, including moderate to severe ulcerative colitis (UC) (1). While the efficacy of UPA has been demonstrated in clinical trials in UC, real-word (RW) evidence on the effectiveness and safety of UPA in UC remains scarce (2). Here, we shed light on the clinical and sonographic results after 2 and 8 weeks of UPA induction in a large, multinational RW cohort of UC patients. Methods EUROPE is an ongoing, prospective, non-interventional, multi-country study in patients with active UC who initiate therapy with UPA. The study assesses the early clinical effectiveness and the predictive value of early disease improvements including sonographic parameters for the long-term outcome after 52 and 104 weeks. For this interim analysis, we report clinical and sonographic results at baseline (BL), week 2 (2W) and week 8 (8W) of 124 UC patients with a visit after 8W until August 2023. For 75 patients, sonographic BL data for the most affected bowel segment was available. Results Of the 124 UC patients, most were male (60.5%, n = 75) with a median age and disease duration of 37.5 years (27.5 – 50.9) and 6.58 years (2.40–12.13). Almost half of all patients had a pancolitis (48.4%, n = 60) The vast majority of patients was bio-experienced (85.5%, n = 106), a third had been exposed to ≥ 3 biologicals (28.2%, n = 35). At BL, patients had a median bowel wall thickness (BWT) of 5.0 mm (3.8-7.0) in the sigmoid colon. It was the most affected segment in 44.4% of patients (n = 55). Disease activity per paMayo score was 3.0 (2.0-5.0) points, with 72.6% (n = 90) and 38.8% (n = 48) of patients reporting ≥ 3 more stools than usual/day and blood in most stools or bleeding without stool, respectively. At 2W after UPA induction, stool frequency and rectal bleeding substantially improved as reflected by the rate of patients in symptomatic remission significantly increasing from 16.9% (n = 21) at BL to 43.5% (n = 54) at 2W and to 64.5% (n = 80) at W8 (both p &lt; 0.001 vs. BL, fig.1). BWT was reduced significantly as early as 2W (n = 48; p &lt; 0.001) and was ≤ 3mm in more than half of all patients. Considering the overall population, 156 patients were included in the safety analysis. Of these, 23.7% (n = 37) experienced an adverse event of which most were non-serious. Conclusion In this first interim analysis of the EUROPE study, UPA treatment in UC was associated with early clinical and sonographic improvement, with most patients achieving symptomatic remission and/or normalization of BWT by week 8 of treatment. 1-SmPC Upadacitinib 2-Danese, Vermeire et al. Lancet. 2022 Jun 4;399(10341):2113-2128","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":"139559202","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/jjad212.0788
S Vermeire, P Dewint, M Vansteelant, M Peterka, D Štěpek, J Kierkuś, A Wiernicka, P Napora, Ł Wolański, A Kopoń, F Magro, I Pinheiro, S Possemiers, L Haazen, S Bolca
Background Treatment options for patients with mild to moderate ulcerative colitis (UC) failing 5-ASA are limited. MH002 is an optimized consortium of 6 non-pathogenic, well-characterized commensal bacteria with immune modulating, wound healing and gut barrier protective effects. This study evaluated the safety, efficacy, and mechanistic effects of MH002 in mild to moderate UC. Methods In this 2:1-randomized, double-blind, placebo-controlled first-in-disease study (EudraCT 2020-001355-33), 45 patients with mild to moderate active UC (Modified Mayo Score [MMS] =4-8 but including Mayo Endoscopic Sub-score [MES] ≥2) received treatment with 400mg MH002 or placebo (PBO) once daily for 8 wks. Full colonoscopies with biopsies were performed at baseline and wk8, biopsies and endoscopy videos were scored by blinded central readers. The primary endpoint was the rate of treatment-emergent adverse events (TEAEs). Exploratory efficacy endpoints included clinical remission (MMS ≤2 with all sub-scores ≤1 and rectal bleeding sub-score =0), endoscopic improvement (MES ≤1), and UC-100 and biomarker normalisation (C-reactive protein [CRP] ≤5mg/L, faecal calprotectin [FCP] ≤250mg/kg). Changes from baseline (CFBL) in MES and stool consistency (Bristol Stool Form Scale) were also evaluated. Results MH002 was safe and well tolerated: a TEAE was reported in 11/31 (35%) patients with MH002 and in 8/14 (57%) with PBO. Most TEAEs were mild and unrelated to study treatment. Early discontinuations (7/45; 16%) occurred similarly in both groups. At wk8, patients achieved clinical remission, endoscopic improvement, and biomarker improvements at higher rates with MH002 vs PBO (Table 1). Clinical remission rates were 14% for MH002 vs 7% for PBO (Per-protocol Set [PPS]: 18% vs 0%). Significant differences in favour of MH002 over PBO were seen in the CFBL for MES at wk8 (P=0.05, 1-sided Wilcoxon) and for stool consistency at wk2 (P=0.0057, 1-sided Student t). In total, 14/45 (31%) and 36/42 (86%) patients had elevated CRP and FCP levels at baseline, resp. Of these, more patients treated with MH002 achieved normalisation at wk8 (CRP: 60% vs 25%; FCP: 36% vs 15%). Decreases in FCP and stool consistency with MH002 were observed as early as wk2 and were greater than with PBO through wk8 (Fig 1). Conclusion MH002 treatment was safe and well tolerated and resulted in clinically meaningful improvements in disease activity and inflammatory parameters. MH002 therefore represents a promising new treatment for mild to moderate UC patients insufficiently controlled with 5ASA. These results warrant further development in a phase 2/3 study.
{"title":"P658 Safety and efficacy of MH002, an optimized live biotherapeutic product, for the treatment of mild to moderate ulcerative colitis: a first-in-disease, double-blind, randomized clinical trial","authors":"S Vermeire, P Dewint, M Vansteelant, M Peterka, D Štěpek, J Kierkuś, A Wiernicka, P Napora, Ł Wolański, A Kopoń, F Magro, I Pinheiro, S Possemiers, L Haazen, S Bolca","doi":"10.1093/ecco-jcc/jjad212.0788","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0788","url":null,"abstract":"Background Treatment options for patients with mild to moderate ulcerative colitis (UC) failing 5-ASA are limited. MH002 is an optimized consortium of 6 non-pathogenic, well-characterized commensal bacteria with immune modulating, wound healing and gut barrier protective effects. This study evaluated the safety, efficacy, and mechanistic effects of MH002 in mild to moderate UC. Methods In this 2:1-randomized, double-blind, placebo-controlled first-in-disease study (EudraCT 2020-001355-33), 45 patients with mild to moderate active UC (Modified Mayo Score [MMS] =4-8 but including Mayo Endoscopic Sub-score [MES] ≥2) received treatment with 400mg MH002 or placebo (PBO) once daily for 8 wks. Full colonoscopies with biopsies were performed at baseline and wk8, biopsies and endoscopy videos were scored by blinded central readers. The primary endpoint was the rate of treatment-emergent adverse events (TEAEs). Exploratory efficacy endpoints included clinical remission (MMS ≤2 with all sub-scores ≤1 and rectal bleeding sub-score =0), endoscopic improvement (MES ≤1), and UC-100 and biomarker normalisation (C-reactive protein [CRP] ≤5mg/L, faecal calprotectin [FCP] ≤250mg/kg). Changes from baseline (CFBL) in MES and stool consistency (Bristol Stool Form Scale) were also evaluated. Results MH002 was safe and well tolerated: a TEAE was reported in 11/31 (35%) patients with MH002 and in 8/14 (57%) with PBO. Most TEAEs were mild and unrelated to study treatment. Early discontinuations (7/45; 16%) occurred similarly in both groups. At wk8, patients achieved clinical remission, endoscopic improvement, and biomarker improvements at higher rates with MH002 vs PBO (Table 1). Clinical remission rates were 14% for MH002 vs 7% for PBO (Per-protocol Set [PPS]: 18% vs 0%). Significant differences in favour of MH002 over PBO were seen in the CFBL for MES at wk8 (P=0.05, 1-sided Wilcoxon) and for stool consistency at wk2 (P=0.0057, 1-sided Student t). In total, 14/45 (31%) and 36/42 (86%) patients had elevated CRP and FCP levels at baseline, resp. Of these, more patients treated with MH002 achieved normalisation at wk8 (CRP: 60% vs 25%; FCP: 36% vs 15%). Decreases in FCP and stool consistency with MH002 were observed as early as wk2 and were greater than with PBO through wk8 (Fig 1). Conclusion MH002 treatment was safe and well tolerated and resulted in clinically meaningful improvements in disease activity and inflammatory parameters. MH002 therefore represents a promising new treatment for mild to moderate UC patients insufficiently controlled with 5ASA. These results warrant further development in a phase 2/3 study.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559216","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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