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":"13 1","pages":""},"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":"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":"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":"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":"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":"122 1","pages":""},"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}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.0516
A Buisson, A Amiot, M Nachury, R Altwegg, M Serrero, T Guilmoteau, X Treton, L Caillo, L Vuitton, G Bouguen, B Pereira, M Fumery
Background STRIDE 2 recommendations define clinical remission as no rectal bleeding and normalization of stool frequency in patients with ulcerative colitis (UC), without including bowel urgency (BU) despite its negative impact on quality of life. In this large multicenter cohort, we aimed to assess whether the persistence of BU after induction therapy is independently associated with poor long-term outcomes in patients with UC. Methods From a multicenter retrospective study, we included consecutive UC adult patients previously exposed to at least one anti-TNF agent, with partial Mayo score (pMS) > 2, who started biologics or small molecules between Jan2019 and June2022. BU was defined as a binary criterion based on the SCCAI definition. The primary endpoint was the time to drug discontinuation due to active UC. Secondary endpoints were time to relapse, time to colectomy as well as steroid-free clinical remission (pMS ≤ 2) (CFREM), endoscopic remission (CFREM + Mayo endoscopic score (MES) ≤ 1), and mucosal healing (CFREM + MES ≤ 1 + histological remission i.e. Nancy index ≤ 1) at last follow-up. Results Among 473 patients with UC, 270 were assessed for BU after induction therapy (week 16) (mean age 43.0±17.0 years-old, median UC duration 6 [3-11] years, female gender=54.0%, pancolitis=45.9%). The median follow-up was 14 [8-22] months. The rate of CFREM after induction therapy was 54.4% (147/270) while 21.5% (58/270) had remaining bowel urgencies after induction therapy. Among the 147 patients achieving remission after induction therapy, 12 had persistent BU (8.2%), while 62.6% (77/123) of patients with no CFREM after induction therapy did not have any BU. The agreements between BU and rectal bleeding (75.2%, κ-coefficient = 0.33±0.06) or normalization of stools frequency (67.9%,κ-coefficient = 0.35±0.05) were mild. Among the patients with persistent BU after induction therapy, only 3.7% had no endoscopic activity (MES = 0). In multivariable analyses including CFREM at week 16, persistence of BU after induction therapy was independently associated with the time to drug discontinuation (HR=2.0[1.1-3.5], p=0.016) and colectomy (HR=4.4[2.3-8.4], p<0.001), and absence of mucosal healing (OR = 5.0[1.1-24.8], p=0.046) at last follow-up. A trend was also observed regarding the association between remaining BU after induction therapy and no CFREM (OR=6.1[0.8-48.0], p=0.085) or absence of endoscopic remission (OR=2.4[0.9-6.1], p=0.077) at last follow-up. Conclusion Persistence of BU despite clinical remission is associated with higher risk of drug discontinuation due to active UC, colectomy and lower likelihood of mucosal healing. Bowel urgency should be implemented into international guidelines to define clinical remission in patients with UC.
{"title":"P386 Persistence of bowel urgency despite clinical remission after induction therapy is associated with unfavorable long-term outcomes in patients with ulcerative colitis: results from the multicenter UC-RGENCY study","authors":"A Buisson, A Amiot, M Nachury, R Altwegg, M Serrero, T Guilmoteau, X Treton, L Caillo, L Vuitton, G Bouguen, B Pereira, M Fumery","doi":"10.1093/ecco-jcc/jjad212.0516","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0516","url":null,"abstract":"Background STRIDE 2 recommendations define clinical remission as no rectal bleeding and normalization of stool frequency in patients with ulcerative colitis (UC), without including bowel urgency (BU) despite its negative impact on quality of life. In this large multicenter cohort, we aimed to assess whether the persistence of BU after induction therapy is independently associated with poor long-term outcomes in patients with UC. Methods From a multicenter retrospective study, we included consecutive UC adult patients previously exposed to at least one anti-TNF agent, with partial Mayo score (pMS) &gt; 2, who started biologics or small molecules between Jan2019 and June2022. BU was defined as a binary criterion based on the SCCAI definition. The primary endpoint was the time to drug discontinuation due to active UC. Secondary endpoints were time to relapse, time to colectomy as well as steroid-free clinical remission (pMS ≤ 2) (CFREM), endoscopic remission (CFREM + Mayo endoscopic score (MES) ≤ 1), and mucosal healing (CFREM + MES ≤ 1 + histological remission i.e. Nancy index ≤ 1) at last follow-up. Results Among 473 patients with UC, 270 were assessed for BU after induction therapy (week 16) (mean age 43.0±17.0 years-old, median UC duration 6 [3-11] years, female gender=54.0%, pancolitis=45.9%). The median follow-up was 14 [8-22] months. The rate of CFREM after induction therapy was 54.4% (147/270) while 21.5% (58/270) had remaining bowel urgencies after induction therapy. Among the 147 patients achieving remission after induction therapy, 12 had persistent BU (8.2%), while 62.6% (77/123) of patients with no CFREM after induction therapy did not have any BU. The agreements between BU and rectal bleeding (75.2%, κ-coefficient = 0.33±0.06) or normalization of stools frequency (67.9%,κ-coefficient = 0.35±0.05) were mild. Among the patients with persistent BU after induction therapy, only 3.7% had no endoscopic activity (MES = 0). In multivariable analyses including CFREM at week 16, persistence of BU after induction therapy was independently associated with the time to drug discontinuation (HR=2.0[1.1-3.5], p=0.016) and colectomy (HR=4.4[2.3-8.4], p&lt;0.001), and absence of mucosal healing (OR = 5.0[1.1-24.8], p=0.046) at last follow-up. A trend was also observed regarding the association between remaining BU after induction therapy and no CFREM (OR=6.1[0.8-48.0], p=0.085) or absence of endoscopic remission (OR=2.4[0.9-6.1], p=0.077) at last follow-up. Conclusion Persistence of BU despite clinical remission is associated with higher risk of drug discontinuation due to active UC, colectomy and lower likelihood of mucosal healing. Bowel urgency should be implemented into international guidelines to define clinical remission in patients with UC.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559391","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/jjad212.0831
D C Balderramo, J Etchevers, C Fuxman, P Lubrano, M Bellicoso, G Correa, J Trakal, M R Defago, J Montero, M Toro, A Novillo, M Bonardo, N Arancibia, S Motañez, S Quines, S Huernos, A Gil, R Gonzalez, S Goncalves
Background Vedolizumab (VDZ) is a gut-selective integrin inhibitor used to treat Crohn's disease (CD). Most of the information regarding real-life data on response to VDZ has been published from North America and Europe cohorts and there is scarce information from Latin America related to effectiveness of VDZ in patients with CD. The aims of this study were: i) to describe the clinical characteristics of patients with CD who received VDZ, ii) to know in which biologic line VDZ was indicated, and iii) to evaluate the clinical response at one year and the persistence of treatment during follow-up. Methods A retrospective multicenter study was conducted in 18 Argentinean centers. We included CD adult patients (age ≥18y) who started VDZ between 01/06/2015 and 31/10/2023 and completed at least VDZ induction. Baseline demographic characteristics, response at 12 months (m), need for optimization, and treatment persistence during follow-up were assessed. Logistic regression was used to evaluate predictors for response at 12m and treatment persistence. Results A total of 113 CD patients (57% male), mean age 52 years (range 18-87 years) were included. Colonic (47%) and ileal (29%) were the most frequent CD involvement. Inflammatory (68%) was the most frequent phenotype compared to stenosing (23%) and fistulizing (9%). Perianal involvement was present in 9% of patients. VDZ was indicated as first-line in 61 (54%) patients, second-line 31 (27.4%) patients, third line 17 (15%) patients, and fourth-line 4 (3.5%) patients. At 12 m of follow-up, clinical remission was observed in 37 (32.7%) patients and clinical response in 56 (49.6%) patients. Eighteen (15.9%) patients presented a lack of response/primary failure. Adverse effects leading to VDZ discontinuation prior to 12m occurred in 2 (1.8%) patients. Mean follow-up time in those patients that achieved clinical remission/response at 12m was 23 (SD 15) m. Thirty-five (37.6%) of those patients required dose optimization and 69 (74.2%) persisted on treatment during follow-up. Male sex (OR 2.93, 95%CI 1.04-8.26) and inflammatory phenotype (OR 5.37, 95%CI 1.16-24.9) were independent predictors for clinical response/remission at 12m. VDZ in first-line (OR 3, 95%CI 1.05-8.52) and inflammatory phenotype (OR 2.96, 95%CI 1.07-8.22) were independent predictors for treatment persistence in those patients that achieved clinical remission/response at 12m. Conclusion This is the first real-life multicenter study on the effectiveness of VZD in CD in Argentina and one of the largest in Latin America. VDZ showed an effective therapeutic option in a real-life setting. A higher efficacy was observed in males, inflammatory phenotype and in biologic-naïve patients.
{"title":"P701 Evaluation of the effectiveness of vedolizumab in patients with Crohn's disease: a multicenter real-life study from Argentina","authors":"D C Balderramo, J Etchevers, C Fuxman, P Lubrano, M Bellicoso, G Correa, J Trakal, M R Defago, J Montero, M Toro, A Novillo, M Bonardo, N Arancibia, S Motañez, S Quines, S Huernos, A Gil, R Gonzalez, S Goncalves","doi":"10.1093/ecco-jcc/jjad212.0831","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0831","url":null,"abstract":"Background Vedolizumab (VDZ) is a gut-selective integrin inhibitor used to treat Crohn's disease (CD). Most of the information regarding real-life data on response to VDZ has been published from North America and Europe cohorts and there is scarce information from Latin America related to effectiveness of VDZ in patients with CD. The aims of this study were: i) to describe the clinical characteristics of patients with CD who received VDZ, ii) to know in which biologic line VDZ was indicated, and iii) to evaluate the clinical response at one year and the persistence of treatment during follow-up. Methods A retrospective multicenter study was conducted in 18 Argentinean centers. We included CD adult patients (age ≥18y) who started VDZ between 01/06/2015 and 31/10/2023 and completed at least VDZ induction. Baseline demographic characteristics, response at 12 months (m), need for optimization, and treatment persistence during follow-up were assessed. Logistic regression was used to evaluate predictors for response at 12m and treatment persistence. Results A total of 113 CD patients (57% male), mean age 52 years (range 18-87 years) were included. Colonic (47%) and ileal (29%) were the most frequent CD involvement. Inflammatory (68%) was the most frequent phenotype compared to stenosing (23%) and fistulizing (9%). Perianal involvement was present in 9% of patients. VDZ was indicated as first-line in 61 (54%) patients, second-line 31 (27.4%) patients, third line 17 (15%) patients, and fourth-line 4 (3.5%) patients. At 12 m of follow-up, clinical remission was observed in 37 (32.7%) patients and clinical response in 56 (49.6%) patients. Eighteen (15.9%) patients presented a lack of response/primary failure. Adverse effects leading to VDZ discontinuation prior to 12m occurred in 2 (1.8%) patients. Mean follow-up time in those patients that achieved clinical remission/response at 12m was 23 (SD 15) m. Thirty-five (37.6%) of those patients required dose optimization and 69 (74.2%) persisted on treatment during follow-up. Male sex (OR 2.93, 95%CI 1.04-8.26) and inflammatory phenotype (OR 5.37, 95%CI 1.16-24.9) were independent predictors for clinical response/remission at 12m. VDZ in first-line (OR 3, 95%CI 1.05-8.52) and inflammatory phenotype (OR 2.96, 95%CI 1.07-8.22) were independent predictors for treatment persistence in those patients that achieved clinical remission/response at 12m. Conclusion This is the first real-life multicenter study on the effectiveness of VZD in CD in Argentina and one of the largest in Latin America. VDZ showed an effective therapeutic option in a real-life setting. A higher efficacy was observed in males, inflammatory phenotype and in biologic-naïve patients.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"163 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559395","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/jjad212.0303
P Riviere, M Dallmann-Sauer, R Enaud, T Bessissow, X Treton, M Uzzan, F Poullenot, F Zerbib, D Laharie, E Schurr
Background Limited understanding exists regarding the pathogenesis of acute severe ulcerative colitis (UC). Microorganisms are proposed as potential triggers due to the resemblances to infectious colitis and the essential role played by gut microbiota in UC-related inflammation. Our aim was to identify microbiome elements and host factors associated with acute severe UC. Methods This was a prospective study across three referral centers comparing two UC patient groups: acute severe hospitalized UC (as per Truelove and Witts criteria) and non-severe UC. We analyzed gut microbiota using 16S rRNA gene sequencing and conducted single-cell RNA-Seq on rectal biopsies in a subgroup of patients to uncover cellular subtypes and pathways involved in mucosal inflammation. We utilized whole blood RNA-Seq to investigate the host pathways involved in mediating systemic inflammation. Results Forty-one patients (23 (56%) female, median (interquartile range IQR) age 42 (34 – 57) years were included: 19 with acute severe UC and 22 with non-severe UC. Compared to patients with non-severe UC, those with acute severe UC displayed distinct gut microbiota with reduced diversity, increased Proteobacteria (Escherichia/Shigella genus), and decreased Lachnospiraceae and Ruminococcaceae. In severe cases (n=4 - 13,047 cells), single-cell RNA-Seq analysis of rectal biopsies revealed distinctive patterns compared to non-severe cases (n=5 - 18,433 cells): plasmablasts showed an altered transcriptomic profile with heightened IgG expression, and there was an expanded cluster of interleukin (IL) 26 expressing T cell population. Innate immune cells exhibited a pro-inflammatory profile marked by increased expression of the IL1B gene. In blood samples, we observed no distinct differentiation of transcriptomic profiles between severe and non-severe cases. Conclusion Our multi-omics study reveals key cellular and bacterial components in acute severe UC pathogenesis. We identified Proteobacteria, especially Escherichia coli as a potential pathobiont in acute severe UC. At the colonic level, we observed an increased IgG/IgA ratio, while both T cells and innate immune cells indicated a pro-Th17 mucosal environment. Enhanced systemic inflammation in acute severe UC was not reflected by specific changes in immune circulating cells. These insights may pave the way for future research focusing on microbiome modulation, interventions targeting plasmablasts, or nuanced inhibition of the Th17/IL-23 axis in acute severe UC.
{"title":"P173 Characterization of the gut microbiota and the colonic immune response in acute severe ulcerative colitis : the multi-omics ITAC project","authors":"P Riviere, M Dallmann-Sauer, R Enaud, T Bessissow, X Treton, M Uzzan, F Poullenot, F Zerbib, D Laharie, E Schurr","doi":"10.1093/ecco-jcc/jjad212.0303","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0303","url":null,"abstract":"Background Limited understanding exists regarding the pathogenesis of acute severe ulcerative colitis (UC). Microorganisms are proposed as potential triggers due to the resemblances to infectious colitis and the essential role played by gut microbiota in UC-related inflammation. Our aim was to identify microbiome elements and host factors associated with acute severe UC. Methods This was a prospective study across three referral centers comparing two UC patient groups: acute severe hospitalized UC (as per Truelove and Witts criteria) and non-severe UC. We analyzed gut microbiota using 16S rRNA gene sequencing and conducted single-cell RNA-Seq on rectal biopsies in a subgroup of patients to uncover cellular subtypes and pathways involved in mucosal inflammation. We utilized whole blood RNA-Seq to investigate the host pathways involved in mediating systemic inflammation. Results Forty-one patients (23 (56%) female, median (interquartile range IQR) age 42 (34 – 57) years were included: 19 with acute severe UC and 22 with non-severe UC. Compared to patients with non-severe UC, those with acute severe UC displayed distinct gut microbiota with reduced diversity, increased Proteobacteria (Escherichia/Shigella genus), and decreased Lachnospiraceae and Ruminococcaceae. In severe cases (n=4 - 13,047 cells), single-cell RNA-Seq analysis of rectal biopsies revealed distinctive patterns compared to non-severe cases (n=5 - 18,433 cells): plasmablasts showed an altered transcriptomic profile with heightened IgG expression, and there was an expanded cluster of interleukin (IL) 26 expressing T cell population. Innate immune cells exhibited a pro-inflammatory profile marked by increased expression of the IL1B gene. In blood samples, we observed no distinct differentiation of transcriptomic profiles between severe and non-severe cases. Conclusion Our multi-omics study reveals key cellular and bacterial components in acute severe UC pathogenesis. We identified Proteobacteria, especially Escherichia coli as a potential pathobiont in acute severe UC. At the colonic level, we observed an increased IgG/IgA ratio, while both T cells and innate immune cells indicated a pro-Th17 mucosal environment. Enhanced systemic inflammation in acute severe UC was not reflected by specific changes in immune circulating cells. These insights may pave the way for future research focusing on microbiome modulation, interventions targeting plasmablasts, or nuanced inhibition of the Th17/IL-23 axis in acute severe UC.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559397","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/jjad212.0326
H Y Wu, C N Chen, M T Weng, C B Huang, P N Tsao, S C Wei
Background The incidence of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), has exhibited a consistent rise in recent years across Asia and Taiwan. Existing literature suggests that women with IBD may experience suboptimal perinatal outcomes. However, the specific relationship between IBD in pregnant Taiwanese women and the subsequent health outcomes of their newborns remains unclear. This study aims to meticulously examine the association between maternal IBD and perinatal outcomes using extensive and representative health databases in Taiwan. Methods We utilized four large national representative health and welfare databases: 1) Maternal and Child Health Database, 2) Birth Certificate Database, 3) National Health Insurance Database, and 4) Catastrophic Illness Database. Data spanning from 2004 to 2018 were linked using encrypted personal IDs to establish a birth cohort during this period. Mothers identified with a registered IBD diagnosis (CD: ICD 9=555, ICD 10= K50.00-K50.919; UC: ICD 9=556.0-556.6 and 556.8-556.9, ICD 10= K51.00-K51.919) in the Catastrophic Illness Database were defined as cases, with a comparison group of healthy pregnant women matched 1:10 in the same birth year and maternal age. Statistical analyses were done by chi-square tests and conditional logistic regression models. Results Among the 3,059,647 births between 2004 and 2018, 146 newborns (126 UC; 20 CD) were born by mothers with a registered IBD diagnosis (Figure 1). No statistically significant differences were observed in stillbirth, preterm birth, cesarean delivery, low birth weight, small-for-gestational-age (SGA), large-for-gestational-age (LGA), and low Apgar scores when compared to the 1,460 matched healthy mothers (Table 1). The only significant difference was observed in the incidence of hypertensive disorders of pregnancy, with a lower prevalence in the IBD group compared to the control group (4.1% vs. 13.6%; p=0.001). Multivariate conditional logistic regression analysis disclosed no significant differences in the aforementioned perinatal outcomes. Subgroup analysis demonstrated that no difference was noted between the CD and UC groups. Conclusion Through this comprehensive analysis of long-term health and welfare databases in Taiwan, we found comparable perinatal outcomes between women with IBD and matched healthy women. The birth outcomes are also improved compared with previous studies. This may be associated with advancements in medical management for IBD in recent years. Further research is needed to explore the long-term neurodevelopmental outcomes of these newborns.
{"title":"P196 Pregnancy and perinatal outcomes of Inflammatory Bowel Disease mothers in Taiwan - a nationwide health and welfare databases analysis","authors":"H Y Wu, C N Chen, M T Weng, C B Huang, P N Tsao, S C Wei","doi":"10.1093/ecco-jcc/jjad212.0326","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0326","url":null,"abstract":"Background The incidence of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), has exhibited a consistent rise in recent years across Asia and Taiwan. Existing literature suggests that women with IBD may experience suboptimal perinatal outcomes. However, the specific relationship between IBD in pregnant Taiwanese women and the subsequent health outcomes of their newborns remains unclear. This study aims to meticulously examine the association between maternal IBD and perinatal outcomes using extensive and representative health databases in Taiwan. Methods We utilized four large national representative health and welfare databases: 1) Maternal and Child Health Database, 2) Birth Certificate Database, 3) National Health Insurance Database, and 4) Catastrophic Illness Database. Data spanning from 2004 to 2018 were linked using encrypted personal IDs to establish a birth cohort during this period. Mothers identified with a registered IBD diagnosis (CD: ICD 9=555, ICD 10= K50.00-K50.919; UC: ICD 9=556.0-556.6 and 556.8-556.9, ICD 10= K51.00-K51.919) in the Catastrophic Illness Database were defined as cases, with a comparison group of healthy pregnant women matched 1:10 in the same birth year and maternal age. Statistical analyses were done by chi-square tests and conditional logistic regression models. Results Among the 3,059,647 births between 2004 and 2018, 146 newborns (126 UC; 20 CD) were born by mothers with a registered IBD diagnosis (Figure 1). No statistically significant differences were observed in stillbirth, preterm birth, cesarean delivery, low birth weight, small-for-gestational-age (SGA), large-for-gestational-age (LGA), and low Apgar scores when compared to the 1,460 matched healthy mothers (Table 1). The only significant difference was observed in the incidence of hypertensive disorders of pregnancy, with a lower prevalence in the IBD group compared to the control group (4.1% vs. 13.6%; p=0.001). Multivariate conditional logistic regression analysis disclosed no significant differences in the aforementioned perinatal outcomes. Subgroup analysis demonstrated that no difference was noted between the CD and UC groups. Conclusion Through this comprehensive analysis of long-term health and welfare databases in Taiwan, we found comparable perinatal outcomes between women with IBD and matched healthy women. The birth outcomes are also improved compared with previous studies. This may be associated with advancements in medical management for IBD in recent years. Further research is needed to explore the long-term neurodevelopmental outcomes of these newborns.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"65 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559421","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/jjad212.0244
B Verstockt, S Vermeire, L Peyrin-Biroulet, A Yarur, R Panaccione, R Mosig, F Cataldi, S Danese
Background NLRX1 activation reduces inflammation by decreasing oxidative stress and altering cellular metabolism within multiple cell types implicated in ulcerative colitis (UC). Colitis animal models demonstrated reduced disease severity and a phase 1b clinical trial showed signs of rapid symptom and endoscopic improvement in patients with active UC.1, 2 Abdominal pain driven by visceral hypersensitivity may persist in patients even after inflammation has resolved, negatively affecting their quality of life.3, 4 Therapeutic agents which address inflammation, epithelial healing, and visceral hypersensitivity concurrently may provide greater symptomatic relief and improved quality of life as many patients, even in remission, still complain of abdominal pain. We here describe the effects of oral NX-13 in a rat model of visceral hypersensitivity. Methods Rats (n=8) were dosed daily for a period of 3 days with NX-13 or vehicle. Under anesthesia, electrodes were positioned to monitor oblique abdominal muscle contraction and a colonic balloon catheter was inserted intra-anally. Visceral pain was assessed at baseline and 3 h post lipopolysaccharide injection (1 mg/kg subcutaneous) through measuring of visceromotor response (VMR) via electromyogram (EMG) recording and visual assessment of abdominal withdrawal reflex (AWR). Data are represented as median (IQR) and statistical significance determined by non-parametric Mann-Whitney U test. Results Compared to the vehicle control, oral NX-13 delayed the onset of muscle contraction in response to colonic distension in LPS-treated rats. Further, NX-13 treated rats experienced reduced contraction intensity and reduced sustained abdominal muscle contraction period compared to the vehicle control. Specifically, NX-13 decreased the number of AWR during colonic expansion compared to the control group (p=0.01, Fig1A). Moreover, NX-13 desensitized the VMR response by numerically increasing the minimum volume of the colonic distension balloon required to induce significant VMR. The mean minimum volume of water injected required to induce significant VMR increased 23%, from 650 μL in the vehicle group to 800 μL in the NX-13 treated rats (p=0.16, Fig1B). Lastly, NX-13 visually reduced the maximum abdominal EMG amplitude during colonic distention (p=0.19, Fig1C). Conclusion Adequate management of persistent pain in IBD patients with or without active bowel inflammation remains an unmet need in the treatment of IBD. The potential for NX-13 to specifically reduce visceral hypersensitivity and abdominal pain will be evaluated further in the ongoing phase 2 human NEXUS trial in patients with UC. 1Leber et al. J Immunol 203(12) 2Peyrin-Biroulet et al. JCC (17)Supp 3Abreu et al. JCC (14)Supp 4Wils et al. J Clin Med 11(15)
{"title":"P114 Role of NLRX1 Agonist NX-13 in Reducing Visceral Hypersensitivity in Preclinical Gastrointestinal Inflammation","authors":"B Verstockt, S Vermeire, L Peyrin-Biroulet, A Yarur, R Panaccione, R Mosig, F Cataldi, S Danese","doi":"10.1093/ecco-jcc/jjad212.0244","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0244","url":null,"abstract":"Background NLRX1 activation reduces inflammation by decreasing oxidative stress and altering cellular metabolism within multiple cell types implicated in ulcerative colitis (UC). Colitis animal models demonstrated reduced disease severity and a phase 1b clinical trial showed signs of rapid symptom and endoscopic improvement in patients with active UC.1, 2 Abdominal pain driven by visceral hypersensitivity may persist in patients even after inflammation has resolved, negatively affecting their quality of life.3, 4 Therapeutic agents which address inflammation, epithelial healing, and visceral hypersensitivity concurrently may provide greater symptomatic relief and improved quality of life as many patients, even in remission, still complain of abdominal pain. We here describe the effects of oral NX-13 in a rat model of visceral hypersensitivity. Methods Rats (n=8) were dosed daily for a period of 3 days with NX-13 or vehicle. Under anesthesia, electrodes were positioned to monitor oblique abdominal muscle contraction and a colonic balloon catheter was inserted intra-anally. Visceral pain was assessed at baseline and 3 h post lipopolysaccharide injection (1 mg/kg subcutaneous) through measuring of visceromotor response (VMR) via electromyogram (EMG) recording and visual assessment of abdominal withdrawal reflex (AWR). Data are represented as median (IQR) and statistical significance determined by non-parametric Mann-Whitney U test. Results Compared to the vehicle control, oral NX-13 delayed the onset of muscle contraction in response to colonic distension in LPS-treated rats. Further, NX-13 treated rats experienced reduced contraction intensity and reduced sustained abdominal muscle contraction period compared to the vehicle control. Specifically, NX-13 decreased the number of AWR during colonic expansion compared to the control group (p=0.01, Fig1A). Moreover, NX-13 desensitized the VMR response by numerically increasing the minimum volume of the colonic distension balloon required to induce significant VMR. The mean minimum volume of water injected required to induce significant VMR increased 23%, from 650 μL in the vehicle group to 800 μL in the NX-13 treated rats (p=0.16, Fig1B). Lastly, NX-13 visually reduced the maximum abdominal EMG amplitude during colonic distention (p=0.19, Fig1C). Conclusion Adequate management of persistent pain in IBD patients with or without active bowel inflammation remains an unmet need in the treatment of IBD. The potential for NX-13 to specifically reduce visceral hypersensitivity and abdominal pain will be evaluated further in the ongoing phase 2 human NEXUS trial in patients with UC. 1Leber et al. J Immunol 203(12) 2Peyrin-Biroulet et al. JCC (17)Supp 3Abreu et al. JCC (14)Supp 4Wils et al. J Clin Med 11(15)","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"163 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559425","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/jjad212.0827
M Belkovsky, B Cohen, J Sommovilla, T Hull, S Holubar
Background Non-conventional strictureplasties, specifically the Finney and Michelassi technique, are bowel-preserving surgical techniques for diffuse jejunoileal Crohn’s Disease (CD). We investigated the association of biologic use during non-conventional strictureplasty for Crohn's jejunoileitis and its short- and long-term outcomes. Methods We conducted a retrospective review of all patients with CD who underwent non-conventional strictureplasty at our centre, e.g., side-to-side antiperistaltic strictureplasty (SSAS) according to the Finney or modified Finney technique, or side-to-side isoperistaltic (SSIS) according to the Michelassi or modified Michelassi techniques from January 2000 to October 2022. Patients were categorized into BIO and NoBIO groups based on their uninterrupted use of biologics until the moment of surgery. Our outcomes of interest were: (a)30-day complications; and (b)surgical recurrence. Statistical analysis was performed using R version 4.3.1. Results A total of 71 patients underwent non-conventional strictureplasty: 80 SSAS and 14 SSIS. Group 1 had 17 patients in which 15 SSAS and 3 SSIS were performed. Group 2 had 54 patients in which 65 SSAS and 11 SSIS were performed. Most patients also underwent concurrent Heineke-Mikulicz strictureplasty in 49 patients (69%) and concurrent small bowel resection in 53 patients (74.6%). The patients in the BIO and NoBIO groups had similar baseline characteristics (Table 1). No differences were observed in perioperative outcomes (Table 2). No difference was observed when comparing surgical recurrence rates, but a longer median time to recurrence was observed in the BIO group (4.7 vs. 4.4 years, p=0.004). Conclusion Biologic use at the time of non-conventional strictureplasty for diffuse jejunoileal Crohn’s disease is safe and is associated with a longer median time to recurrence.
{"title":"P697 Short- and long-term outcomes following biologic use before non-conventional stricureplasty for Crohn’s Jejunoileitis","authors":"M Belkovsky, B Cohen, J Sommovilla, T Hull, S Holubar","doi":"10.1093/ecco-jcc/jjad212.0827","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0827","url":null,"abstract":"Background Non-conventional strictureplasties, specifically the Finney and Michelassi technique, are bowel-preserving surgical techniques for diffuse jejunoileal Crohn’s Disease (CD). We investigated the association of biologic use during non-conventional strictureplasty for Crohn's jejunoileitis and its short- and long-term outcomes. Methods We conducted a retrospective review of all patients with CD who underwent non-conventional strictureplasty at our centre, e.g., side-to-side antiperistaltic strictureplasty (SSAS) according to the Finney or modified Finney technique, or side-to-side isoperistaltic (SSIS) according to the Michelassi or modified Michelassi techniques from January 2000 to October 2022. Patients were categorized into BIO and NoBIO groups based on their uninterrupted use of biologics until the moment of surgery. Our outcomes of interest were: (a)30-day complications; and (b)surgical recurrence. Statistical analysis was performed using R version 4.3.1. Results A total of 71 patients underwent non-conventional strictureplasty: 80 SSAS and 14 SSIS. Group 1 had 17 patients in which 15 SSAS and 3 SSIS were performed. Group 2 had 54 patients in which 65 SSAS and 11 SSIS were performed. Most patients also underwent concurrent Heineke-Mikulicz strictureplasty in 49 patients (69%) and concurrent small bowel resection in 53 patients (74.6%). The patients in the BIO and NoBIO groups had similar baseline characteristics (Table 1). No differences were observed in perioperative outcomes (Table 2). No difference was observed when comparing surgical recurrence rates, but a longer median time to recurrence was observed in the BIO group (4.7 vs. 4.4 years, p=0.004). Conclusion Biologic use at the time of non-conventional strictureplasty for diffuse jejunoileal Crohn’s disease is safe and is associated with a longer median time to recurrence.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559200","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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