Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.0609
S Choi, J H Ji, S J Park, J J Park, J H Cheon, T I Kim, J Park
Background The association of intestinal Behçet’s disease (BD) with the risk of hematologic malignancy is still unclear. We aimed to assess the prevalence and determine risk factors of hematologic malignancy in intestinal BD. Methods Using a cohort of patients with intestinal BD between 1997 and 2021, the prevalence and risk factors of hematologic malignancy were analysed by logistic regression analysis at inflammatory bowel disease centre of Severance Hospital, Seoul, Korea. Results Among 780 intestinal BD patients, 23 patients developed hematologic malignancy. Myelodysplastic syndrome (MDS) (n=12) was the most common hematologic malignancy, followed by aplastic anemia (AA) (n=7), leukemia (n=2), and lymphoma (n=2). Eight patients had developed hematologic malignancy before their intestinal BD diagnosis and 15 patients developed hematologic malignancy after their intestinal BD diagnosis. Of the 772 patients without previous hematologic malignancy, patients smoking history (p-value 0.019, odds ratio [OR] 49.513, 95% confidence interval [CI] 1.925-1273.4), history of at least one emergency room (ER) visit (p-value 0.025, OR 26.360, CI 1.501-462.92), and albumin lower than 3.3g/dL (p-value 0.046, OR 603.013, CI 0.108-328191.23) at diagnosis were positively associated with subsequent hematologic malignancy. Body mass index (BMI) (p-value 0.030, OR 0.569, CI 0.342-0.947) was negatively associated with hematologic malignancy. Conclusion The physicians who care for intestinal BD patients with risk factors should be aware and provide careful monitoring of the elevated risk of hematologic malignancy.
{"title":"P479 The prevalence and risk factors of hematologic malignancy in patients with intestinal Behçet’s disease","authors":"S Choi, J H Ji, S J Park, J J Park, J H Cheon, T I Kim, J Park","doi":"10.1093/ecco-jcc/jjad212.0609","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0609","url":null,"abstract":"Background The association of intestinal Behçet’s disease (BD) with the risk of hematologic malignancy is still unclear. We aimed to assess the prevalence and determine risk factors of hematologic malignancy in intestinal BD. Methods Using a cohort of patients with intestinal BD between 1997 and 2021, the prevalence and risk factors of hematologic malignancy were analysed by logistic regression analysis at inflammatory bowel disease centre of Severance Hospital, Seoul, Korea. Results Among 780 intestinal BD patients, 23 patients developed hematologic malignancy. Myelodysplastic syndrome (MDS) (n=12) was the most common hematologic malignancy, followed by aplastic anemia (AA) (n=7), leukemia (n=2), and lymphoma (n=2). Eight patients had developed hematologic malignancy before their intestinal BD diagnosis and 15 patients developed hematologic malignancy after their intestinal BD diagnosis. Of the 772 patients without previous hematologic malignancy, patients smoking history (p-value 0.019, odds ratio [OR] 49.513, 95% confidence interval [CI] 1.925-1273.4), history of at least one emergency room (ER) visit (p-value 0.025, OR 26.360, CI 1.501-462.92), and albumin lower than 3.3g/dL (p-value 0.046, OR 603.013, CI 0.108-328191.23) at diagnosis were positively associated with subsequent hematologic malignancy. Body mass index (BMI) (p-value 0.030, OR 0.569, CI 0.342-0.947) was negatively associated with hematologic malignancy. Conclusion The physicians who care for intestinal BD patients with risk factors should be aware and provide careful monitoring of the elevated risk of hematologic malignancy.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"155 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559434","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/jjad212.0158
Y Yasutomi, A Chiba, K Haga, G Murayama, A Makiyama, T Kuga, A Nagahara, T Nagaishi, S Miyake
Background It is known that the mucosal-associated invariant T (MAIT) cells are the innate-like T cells that are restricted by the major histocompatibility complex-related molecule 1 (MR1), and that these cells express a semi-invariant T cell receptor. We have previously reported that the activation status of the circulating MAIT cells in patients with Ulcerative Colitis (UC) is associated with disease activity, and these cells infiltrate the inflamed colonic mucosa. These findings imply that MAIT cells are involved in the pathogenesis of Inflammatory Bowel Disease (IBD). However, the role of MAIT cells in the setting of IBD has not been revealed. Therefore, we investigated the role of MAIT cells in an animal model of UC. Methods To this end, we utilized MR1 deficient mice (MR1-/-), which lack MAIT cells, and isobutyl 6-formyl pterin (i6-FP), which is a synthetic antagonistic MR1 ligand. MR1-/- on the C57BL/6 background, their littermate wild-type controls, and C57BL/6 mice were sensitized by rectal administration of oxazolone to induce colitis. These were then administered an oral i6-FP. Splenocytes (SPL) and colonic lamina propria lymphocytes (LPL) were isolated from mice receiving i6-FP to measure cytokine production. MR1-/-, i6-FP-treated mice and their controls were orally administered FITC-dextran to analyze intestinal permeability. The peripheral blood mononuclear cells (PBMC) from the patients with UC were also isolated to study the effect of i6-FP on cytokine production by MAIT cells. Results MR1 deficiency or i6-FP treatment resulted in reduced severity of oxazolone-induced colitis. Mice treated with i6-FP resulted in reduced MAIT cell production of pro-inflammatory cytokines such as IFN-g and TNF in both SPL and colonic LPL. Similar results were also observed in PBMC isolated from the patients with UC when incubated with i6-FP. Although MR1 deficiency resulted in increased intestinal permeability, i6-FP administration did not affect gut integrity in mice. Conclusion The current studies indicate that MAIT cells have a pathogenic role in colitis and suppressing activation of these cells may reduce the severity of colitis without affecting gut integrity. Thus, MAIT cells may be potential therapeutic targets for IBD including UC.
{"title":"P028 A pathogenic role of activated mucosal-associated invariant T cells in an animal model of Inflammatory Bowel Disease","authors":"Y Yasutomi, A Chiba, K Haga, G Murayama, A Makiyama, T Kuga, A Nagahara, T Nagaishi, S Miyake","doi":"10.1093/ecco-jcc/jjad212.0158","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0158","url":null,"abstract":"Background It is known that the mucosal-associated invariant T (MAIT) cells are the innate-like T cells that are restricted by the major histocompatibility complex-related molecule 1 (MR1), and that these cells express a semi-invariant T cell receptor. We have previously reported that the activation status of the circulating MAIT cells in patients with Ulcerative Colitis (UC) is associated with disease activity, and these cells infiltrate the inflamed colonic mucosa. These findings imply that MAIT cells are involved in the pathogenesis of Inflammatory Bowel Disease (IBD). However, the role of MAIT cells in the setting of IBD has not been revealed. Therefore, we investigated the role of MAIT cells in an animal model of UC. Methods To this end, we utilized MR1 deficient mice (MR1-/-), which lack MAIT cells, and isobutyl 6-formyl pterin (i6-FP), which is a synthetic antagonistic MR1 ligand. MR1-/- on the C57BL/6 background, their littermate wild-type controls, and C57BL/6 mice were sensitized by rectal administration of oxazolone to induce colitis. These were then administered an oral i6-FP. Splenocytes (SPL) and colonic lamina propria lymphocytes (LPL) were isolated from mice receiving i6-FP to measure cytokine production. MR1-/-, i6-FP-treated mice and their controls were orally administered FITC-dextran to analyze intestinal permeability. The peripheral blood mononuclear cells (PBMC) from the patients with UC were also isolated to study the effect of i6-FP on cytokine production by MAIT cells. Results MR1 deficiency or i6-FP treatment resulted in reduced severity of oxazolone-induced colitis. Mice treated with i6-FP resulted in reduced MAIT cell production of pro-inflammatory cytokines such as IFN-g and TNF in both SPL and colonic LPL. Similar results were also observed in PBMC isolated from the patients with UC when incubated with i6-FP. Although MR1 deficiency resulted in increased intestinal permeability, i6-FP administration did not affect gut integrity in mice. Conclusion The current studies indicate that MAIT cells have a pathogenic role in colitis and suppressing activation of these cells may reduce the severity of colitis without affecting gut integrity. Thus, MAIT cells may be potential therapeutic targets for IBD including UC.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"120 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559199","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/jjad212.1219
G Bröms, A Forss, J Eriksson, M Linder, C Eriksson, J Askling, J Halfvarson, J F Ludvigsson, O Olen
Background Studies from mainly before the wide use of targeted therapies and guidelines for thromboprophylaxis indicate that patients with inflammatory bowel disease (IBD) are at a doubled risk of venous thromboembolism (VTE). We studied the risk of VTE in a modern-day cohort of patients with IBD, overall and in subgroups of disease characteristics. Methods Using Swedish healthcare registers, we identified a nationwide population-based cohort of 55,252 patients with incident IBD between 2007 and 2021 with a median follow-up time of 6.5 years. Patients were matched by age, sex, calendar year and county of residence with up to ten reference individuals from the general population (N=536,067). The primary outcome was VTE, including pulmonary embolism and deep vein thrombosis. Incidence rates per 1,000 person-years and hazard ratios (HR) were calculated for IBD in general and according to disease subtype, sex, age and disease characteristics at diagnosis. HRs stratified by matching variables (model 1) and additionally adjusted for comorbidities and socioeconomic factors (model 2) were estimated by using Cox regression. Results The incidence rate of VTE among patients with IBD was 5.03 per 1,000 person-years compared with 2.34 per 1,000 person-years among reference individuals (Table 1). This corresponded to a doubled incidence of VTE (HR=2.18, 95% confidence interval (CI)=2.07-2.29, model 1). Adjusting further for covariates in model 2 had only minor effects on the HR. The HR was consistent across IBD subtypes and sex. The relative risk was higher for those with younger age (18-39 years) at IBD diagnosis (HR 2.52, 95% CI: 2.22-2.83) with a risk difference of 1.25 per 1,000 person-years. The IR, 10.64 per 1,000 person-years, and risk difference, 5.42 per 1,000 person-years, was the highest for those with elderly onset (≥60 years) IBD. There was a stronger association for those with extensive ulcerative colitis (E3), primary sclerosing cholangitis, extraintestinal manifestations and perianal disease. HRs for VTE were persistently elevated across follow-up time, but was higher during the first year of follow-up (Figure 1). Conclusion The risk of VTE was doubled in these modern-day data and remained elevated across follow-up time. Disease characteristics associated with higher inflammatory burden at diagnosis and older age are markers of increased risk. This underscores the importance of continuous vigilance and individual assessment of risk factors for VTE in patients with IBD.
{"title":"P1089 Disease characteristics at time of diagnosis of adult onset inflammatory bowel disease and the risk of venous thromboembolism in the modern era – A Swedish nationwide cohort study 2007-2021","authors":"G Bröms, A Forss, J Eriksson, M Linder, C Eriksson, J Askling, J Halfvarson, J F Ludvigsson, O Olen","doi":"10.1093/ecco-jcc/jjad212.1219","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.1219","url":null,"abstract":"Background Studies from mainly before the wide use of targeted therapies and guidelines for thromboprophylaxis indicate that patients with inflammatory bowel disease (IBD) are at a doubled risk of venous thromboembolism (VTE). We studied the risk of VTE in a modern-day cohort of patients with IBD, overall and in subgroups of disease characteristics. Methods Using Swedish healthcare registers, we identified a nationwide population-based cohort of 55,252 patients with incident IBD between 2007 and 2021 with a median follow-up time of 6.5 years. Patients were matched by age, sex, calendar year and county of residence with up to ten reference individuals from the general population (N=536,067). The primary outcome was VTE, including pulmonary embolism and deep vein thrombosis. Incidence rates per 1,000 person-years and hazard ratios (HR) were calculated for IBD in general and according to disease subtype, sex, age and disease characteristics at diagnosis. HRs stratified by matching variables (model 1) and additionally adjusted for comorbidities and socioeconomic factors (model 2) were estimated by using Cox regression. Results The incidence rate of VTE among patients with IBD was 5.03 per 1,000 person-years compared with 2.34 per 1,000 person-years among reference individuals (Table 1). This corresponded to a doubled incidence of VTE (HR=2.18, 95% confidence interval (CI)=2.07-2.29, model 1). Adjusting further for covariates in model 2 had only minor effects on the HR. The HR was consistent across IBD subtypes and sex. The relative risk was higher for those with younger age (18-39 years) at IBD diagnosis (HR 2.52, 95% CI: 2.22-2.83) with a risk difference of 1.25 per 1,000 person-years. The IR, 10.64 per 1,000 person-years, and risk difference, 5.42 per 1,000 person-years, was the highest for those with elderly onset (≥60 years) IBD. There was a stronger association for those with extensive ulcerative colitis (E3), primary sclerosing cholangitis, extraintestinal manifestations and perianal disease. HRs for VTE were persistently elevated across follow-up time, but was higher during the first year of follow-up (Figure 1). Conclusion The risk of VTE was doubled in these modern-day data and remained elevated across follow-up time. Disease characteristics associated with higher inflammatory burden at diagnosis and older age are markers of increased risk. This underscores the importance of continuous vigilance and individual assessment of risk factors for VTE in patients with IBD.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"55 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559205","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/jjad212.0350
O M Nardone, G Calabrese, M Allocca, F Caprioli, E D'Alessandro, M Fantini, S Onali, A Orlando, A Rispo, E Savarino, A Soriano, A Variola, F Castiglione
Background As an objective endpoint in IBD Disease-Modification Trials, measures of disability and health-related quality of life have been proposed. IBD-DISK is an easy-to-use, and self-administered analogic visual tool designed for assessing disability. However, successful dissemination of this tool will require a cultural adaptation and translation process. To date, the IBD-Disk has not been validated in Italian clinical practice. Hence, we aimed to validate the IBD-Disk in an Italian population-based cohort according to the COSMIN recommendations. Methods The IBD-Disk italian translation and validation study was a cross-sectional multicentre study conducted in 8 Italian IBD referral centres. After forward-backward translation into Italian, patients were consecutively recruited from February 2023 to October 2023. Patients completed the following questionnaires: IBD-Disk (at baseline, T0, and after seven days, T1) and IBD-Disability Index (IBD-DI) for disability, IBDQ-32, and SF-36 for quality of life. Validation included assessment of validity, reproducibility, internal consistency. We further investigated the correlation between IBD-Disk and IBD activity and clinical factors associated with IBD-Disk. Results At baseline, 513 patients (237,46.2% CD; 276,53.8% UC) completed the IBD-Disk[Table.1]. Internal consistency was excellent with a Cronbach’s α of 0.93. The intraclass correlation coefficient (ICC) was 0.94 for test-retest (T0 and T1) (p< 0.001). To evaluate construct validity, the IBD-Disk was compared with the IBD-DI, revealing a significant positive correlation (r = 0.70; p < 0.001). Furthermore, it exhibited a positive correlation with both IBDQ-32(r=0.82, p< 0.001) and SF-36(r=0.093, p= 0.035). The overall IBD-Disk median score was 32(12-52), with 219(42.7%) reporting moderate-to-severe disability (IBD-DISK ≥ 40). The IBD-Disk score was significantly higher in patients with active CD disease based on HBI ≥ 5 compared to patients with inactive disease(p < 0.001). Similarly, for UC, patients with active disease, measured with a partial Mayo score ≥2, showed a higher IBD-DISK score than those in clinical remission[Fig.1]. Additionally, moderate-to-severe disability significantly increased in female [OR =2.83; 95% CI(1,97-4,07)] and in patients with active extraintestinal manifestations [OR = 1,71; 95%CI(1,23-2,81) p=0.04]. Conclusion This study validated the IBD-Disk in a large cohort of Italian IBD patients, demonstrating that it is a valid, reliable and responsive tool for quantifying disability. This validation enables the broad implementation of IBD-DISK across Italy, facilitating its integration into the daily clinical management of IBD patients.
{"title":"P220 IBD-Disk: italian translation and validation in a population-based cohort","authors":"O M Nardone, G Calabrese, M Allocca, F Caprioli, E D'Alessandro, M Fantini, S Onali, A Orlando, A Rispo, E Savarino, A Soriano, A Variola, F Castiglione","doi":"10.1093/ecco-jcc/jjad212.0350","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0350","url":null,"abstract":"Background As an objective endpoint in IBD Disease-Modification Trials, measures of disability and health-related quality of life have been proposed. IBD-DISK is an easy-to-use, and self-administered analogic visual tool designed for assessing disability. However, successful dissemination of this tool will require a cultural adaptation and translation process. To date, the IBD-Disk has not been validated in Italian clinical practice. Hence, we aimed to validate the IBD-Disk in an Italian population-based cohort according to the COSMIN recommendations. Methods The IBD-Disk italian translation and validation study was a cross-sectional multicentre study conducted in 8 Italian IBD referral centres. After forward-backward translation into Italian, patients were consecutively recruited from February 2023 to October 2023. Patients completed the following questionnaires: IBD-Disk (at baseline, T0, and after seven days, T1) and IBD-Disability Index (IBD-DI) for disability, IBDQ-32, and SF-36 for quality of life. Validation included assessment of validity, reproducibility, internal consistency. We further investigated the correlation between IBD-Disk and IBD activity and clinical factors associated with IBD-Disk. Results At baseline, 513 patients (237,46.2% CD; 276,53.8% UC) completed the IBD-Disk[Table.1]. Internal consistency was excellent with a Cronbach’s α of 0.93. The intraclass correlation coefficient (ICC) was 0.94 for test-retest (T0 and T1) (p&lt; 0.001). To evaluate construct validity, the IBD-Disk was compared with the IBD-DI, revealing a significant positive correlation (r = 0.70; p &lt; 0.001). Furthermore, it exhibited a positive correlation with both IBDQ-32(r=0.82, p&lt; 0.001) and SF-36(r=0.093, p= 0.035). The overall IBD-Disk median score was 32(12-52), with 219(42.7%) reporting moderate-to-severe disability (IBD-DISK ≥ 40). The IBD-Disk score was significantly higher in patients with active CD disease based on HBI ≥ 5 compared to patients with inactive disease(p &lt; 0.001). Similarly, for UC, patients with active disease, measured with a partial Mayo score ≥2, showed a higher IBD-DISK score than those in clinical remission[Fig.1]. Additionally, moderate-to-severe disability significantly increased in female [OR =2.83; 95% CI(1,97-4,07)] and in patients with active extraintestinal manifestations [OR = 1,71; 95%CI(1,23-2,81) p=0.04]. Conclusion This study validated the IBD-Disk in a large cohort of Italian IBD patients, demonstrating that it is a valid, reliable and responsive tool for quantifying disability. This validation enables the broad implementation of IBD-DISK across Italy, facilitating its integration into the daily clinical management of IBD patients.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559270","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/jjad212.0018
Z Serclova, D Garcia-Olmo, S T Chen, S Wexner, J Panés, C Wu, P Fleshner, B Zhang, J F Colombel, M Song, C McKay, P Nazarey, E Wright, L Raffals
Background Complex perianal fistulas are a serious complication in patients with Crohn’s disease (CD). Darvadstrocel (DVS), a suspension of expanded adult allogeneic adipose-derived mesenchymal stem cells, is approved in Europe and Japan for treatment of complex Crohn’s perianal fistulas (CPF). The global ADMIRE-CD II phase 3 randomized double-blind placebo-controlled study evaluated the efficacy and safety of DVS for treatment of complex CPF. Methods Patients aged 18–75 years with clinically controlled, inactive or mildly active CD and complex CPF (≤2 internal openings [IO] and ≤3 external openings [EOs]) who had an inadequate, or a loss of response to immunosuppressive agents or biologics were included. Patients were randomized 1:1 to receive a local injection of DVS as a single dose (120 x 106 cells/24 mL) or placebo. In all patients, fistula preconditioning included vigorous curettage and seton placement 2–3 weeks before treatment, and seton removal, a further curettage and closure of IOs immediately before treatment. The primary endpoint was combined remission (closure of all treated EOs that were draining at baseline, despite gentle finger compression, and absence of collections >2 cm confirmed by MRI) at 24 weeks. Secondary endpoints included combined remission at 52 weeks, clinical remission (closure of all treated EOs without MRI confirmation) at 24 and 52 weeks, and time to clinical remission at 24 weeks. Safety was monitored up to 52 weeks. Results From 19 Oct 2017 to 26 Jul 2023, 568 patients received DVS (n = 283) or placebo (n = 285) with fistula preconditioning; 56.3% of patients enrolled in Europe and Israel, and 43.7% in North America. Mean (SD) age, sex and race were similar in the DVS and placebo arms (38.4 [11.9] vs 37.7 [10.8] years; 42.8% vs 45.6% female; 85.9% vs 89.1% White). Combined remission rates at 24 weeks did not statistically differ between treatments (48.8% DVS vs 46.3% placebo) and there were no differences in secondary endpoints (Table 1; Figure 1). Based on health authority guidelines, post hoc analyses of patients randomized before COVID-19 (11 March 2020; n = 141 DVS, n = 143 placebo) were performed: combined remission rates at 24 weeks were 46.8% (DVS) and 38.5% (placebo). The safety profile for DVS was consistent with prior studies with no new safety signals (Table 1). Conclusion The efficacy outcomes assessed did not statistically differ between DVS and placebo, and the placebo response rate (with fistula preconditioning) was higher than expected. Post hoc analyses revealed lower placebo response rates in patients randomized before COVID-19 (similar to the pivotal ADMIRE CD I study) than the overall placebo arm. DVS was well tolerated.
背景复杂性肛周瘘是克罗恩病（CD）患者的一种严重并发症。Darvadstrocel（DVS）是一种扩增的成人异体脂肪间充质干细胞悬浮液，已在欧洲和日本获准用于治疗复杂性克罗恩病肛周瘘。全球 ADMIRE-CD II 3 期随机双盲安慰剂对照研究评估了 DVS 治疗复杂性 CPF 的疗效和安全性。方法 纳入年龄为 18-75 岁、临床控制的非活动性或轻度活动性 CD 和复杂 CPF（≤2 个内开口 [IO] 和≤3 个外开口 [EO]）患者，这些患者对免疫抑制剂或生物制剂反应不足或失去反应。患者按 1:1 随机分配接受单剂量局部注射 DVS（120 x 106 cells/24 mL）或安慰剂。在所有患者中，瘘管预处理包括在治疗前2-3周进行剧烈刮宫和放置套管，以及在治疗前立即移除套管、进一步刮宫和关闭IO。主要终点是24周时的综合缓解（所有治疗后的瘘管在基线时均有引流，尽管手指轻轻按压，瘘管仍然闭合，并且经核磁共振成像确认没有>2厘米的积液）。次要终点包括：52周时的综合缓解、24周和52周时的临床缓解（所有治疗过的EO在未经核磁共振成像确认的情况下均已闭合）以及24周时的临床缓解时间。安全性监测持续到 52 周。结果 从2017年10月19日至2023年7月26日，568名患者接受了瘘管预处理的DVS（n = 283）或安慰剂（n = 285）治疗；56.3%的患者在欧洲和以色列入组，43.7%的患者在北美入组。DVS治疗组和安慰剂治疗组的平均（标清）年龄、性别和种族相似（38.4 [11.9] 岁 vs 37.7 [10.8]岁；42.8% vs 45.6%为女性；85.9% vs 89.1%为白人）。24周的综合缓解率在统计学上没有差异（DVS为48.8%，安慰剂为46.3%），次要终点也没有差异（表1；图1）。根据卫生部门的指导方针，对在COVID-19（2020年3月11日；n = 141 DVS，n = 143安慰剂）之前随机接受治疗的患者进行了事后分析：24周时的综合缓解率分别为46.8%（DVS）和38.5%（安慰剂）。DVS的安全性与之前的研究一致，没有出现新的安全信号（表1）。结论 DVS 和安慰剂的疗效评估结果没有统计学差异，安慰剂应答率（瘘管预处理）高于预期。事后分析显示，COVID-19（类似于关键的 ADMIRE CD I 研究）之前随机分组的患者的安慰剂应答率低于整个安慰剂组。DVS 的耐受性良好。
{"title":"OP18 Efficacy and safety of darvadstrocel treatment in patients with complex perianal fistulas and Crohn’s Disease: results from the global ADMIRE-CD II phase 3 study","authors":"Z Serclova, D Garcia-Olmo, S T Chen, S Wexner, J Panés, C Wu, P Fleshner, B Zhang, J F Colombel, M Song, C McKay, P Nazarey, E Wright, L Raffals","doi":"10.1093/ecco-jcc/jjad212.0018","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0018","url":null,"abstract":"Background Complex perianal fistulas are a serious complication in patients with Crohn’s disease (CD). Darvadstrocel (DVS), a suspension of expanded adult allogeneic adipose-derived mesenchymal stem cells, is approved in Europe and Japan for treatment of complex Crohn’s perianal fistulas (CPF). The global ADMIRE-CD II phase 3 randomized double-blind placebo-controlled study evaluated the efficacy and safety of DVS for treatment of complex CPF. Methods Patients aged 18–75 years with clinically controlled, inactive or mildly active CD and complex CPF (≤2 internal openings [IO] and ≤3 external openings [EOs]) who had an inadequate, or a loss of response to immunosuppressive agents or biologics were included. Patients were randomized 1:1 to receive a local injection of DVS as a single dose (120 x 106 cells/24 mL) or placebo. In all patients, fistula preconditioning included vigorous curettage and seton placement 2–3 weeks before treatment, and seton removal, a further curettage and closure of IOs immediately before treatment. The primary endpoint was combined remission (closure of all treated EOs that were draining at baseline, despite gentle finger compression, and absence of collections &gt;2 cm confirmed by MRI) at 24 weeks. Secondary endpoints included combined remission at 52 weeks, clinical remission (closure of all treated EOs without MRI confirmation) at 24 and 52 weeks, and time to clinical remission at 24 weeks. Safety was monitored up to 52 weeks. Results From 19 Oct 2017 to 26 Jul 2023, 568 patients received DVS (n = 283) or placebo (n = 285) with fistula preconditioning; 56.3% of patients enrolled in Europe and Israel, and 43.7% in North America. Mean (SD) age, sex and race were similar in the DVS and placebo arms (38.4 [11.9] vs 37.7 [10.8] years; 42.8% vs 45.6% female; 85.9% vs 89.1% White). Combined remission rates at 24 weeks did not statistically differ between treatments (48.8% DVS vs 46.3% placebo) and there were no differences in secondary endpoints (Table 1; Figure 1). Based on health authority guidelines, post hoc analyses of patients randomized before COVID-19 (11 March 2020; n = 141 DVS, n = 143 placebo) were performed: combined remission rates at 24 weeks were 46.8% (DVS) and 38.5% (placebo). The safety profile for DVS was consistent with prior studies with no new safety signals (Table 1). Conclusion The efficacy outcomes assessed did not statistically differ between DVS and placebo, and the placebo response rate (with fistula preconditioning) was higher than expected. Post hoc analyses revealed lower placebo response rates in patients randomized before COVID-19 (similar to the pivotal ADMIRE CD I study) than the overall placebo arm. DVS was well tolerated.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559380","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/jjad212.0719
C Harris, T Gee, A Barcan, Y Yanagisawa, M Brown, J N Gordon
Background Upadacitinib is a selective Janus kinase inhibitor that has recently been approved in England for the treatment of ulcerative colitis (UC) and Crohn’s disease (CD) though real-world data is lacking. Furthermore, there is very limited information available on patient reported experiences of treatment with a small molecule compared with biological therapies. The object of this study was to provide real-world data on the efficacy of upadacitinib in the treatment of IBD in conjugation with collecting specific patient-reported feedback on acceptability and experience of treatment with upadacitinib. Methods We prospectively collected data on all IBD patients treated with upadacitinib between November 2022 and November 2023 in a large NHS Trust serving approximately 1% of the population of England. The primary objective was to assess patient response to induction at 8 weeks (UC) and 12 weeks (CD). Demographic details, biochemical markers (faecal calprotectin and CRP) and disease activity scores were recorded. We also undertook a bespoke anonymised electronic survey to assess the patient experience and views on treatment with upadacitinib in comparison to previous treatments. Results Forty-two patients were included in the study (34 UC/8 CD). The average age was 41 (range 18-76) and 27 (64%) were male. 11/34 UC patients were biologic naïve. All CD patients were biologic experienced with the majority exposed to an anti-TNF, vedolizumab and ustekinumab. Overall, 34/40 (85%) patients responded to induction treatment based on disease activity scores (27 UC, 7CD), with 68% (22 UC, 5 CD) in remission. Data was missing for two patients. Response rates were similar between biologic naïve and biologic exposed patients (82% and 86% respectively). In the UC cohort, mean calprotectin at baseline improved from 1718ug/g (range 8-6000ug/g) to 311ug/g (4-3014ug/g). In the CD cohort, mean calprotectin improved from 1719ug/g (115-5874ug/g) to 314ug/g (4-917ug/g). 3/42 (7%) of patients discontinued upadacitinib due to disease progression with the remaining 93% continuing treatment. Our patient survey results revealed very high satisfaction with treatment (85%), with the vast majority preferring treatment with upadacitinib to their previous biological therapy. Conclusion In this real-world study, induction therapy with upadacitinib was well tolerated and demonstrated good efficacy with excellent response and remission rates in a mixed patient cohort that included many with highly refractory disease. No unexpected safety signals were seen. The patient experience was overwhelmingly positive. If this data is replicated in larger studies there is an increasingly strong rationale for introducing upadacitinib earlier in the sequencing of advanced therapies.
{"title":"P589 Real-world data on upadacitinib in the treatment of inflammatory bowel disease: safe and highly effective with extremely positive patient feedback","authors":"C Harris, T Gee, A Barcan, Y Yanagisawa, M Brown, J N Gordon","doi":"10.1093/ecco-jcc/jjad212.0719","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0719","url":null,"abstract":"Background Upadacitinib is a selective Janus kinase inhibitor that has recently been approved in England for the treatment of ulcerative colitis (UC) and Crohn’s disease (CD) though real-world data is lacking. Furthermore, there is very limited information available on patient reported experiences of treatment with a small molecule compared with biological therapies. The object of this study was to provide real-world data on the efficacy of upadacitinib in the treatment of IBD in conjugation with collecting specific patient-reported feedback on acceptability and experience of treatment with upadacitinib. Methods We prospectively collected data on all IBD patients treated with upadacitinib between November 2022 and November 2023 in a large NHS Trust serving approximately 1% of the population of England. The primary objective was to assess patient response to induction at 8 weeks (UC) and 12 weeks (CD). Demographic details, biochemical markers (faecal calprotectin and CRP) and disease activity scores were recorded. We also undertook a bespoke anonymised electronic survey to assess the patient experience and views on treatment with upadacitinib in comparison to previous treatments. Results Forty-two patients were included in the study (34 UC/8 CD). The average age was 41 (range 18-76) and 27 (64%) were male. 11/34 UC patients were biologic naïve. All CD patients were biologic experienced with the majority exposed to an anti-TNF, vedolizumab and ustekinumab. Overall, 34/40 (85%) patients responded to induction treatment based on disease activity scores (27 UC, 7CD), with 68% (22 UC, 5 CD) in remission. Data was missing for two patients. Response rates were similar between biologic naïve and biologic exposed patients (82% and 86% respectively). In the UC cohort, mean calprotectin at baseline improved from 1718ug/g (range 8-6000ug/g) to 311ug/g (4-3014ug/g). In the CD cohort, mean calprotectin improved from 1719ug/g (115-5874ug/g) to 314ug/g (4-917ug/g). 3/42 (7%) of patients discontinued upadacitinib due to disease progression with the remaining 93% continuing treatment. Our patient survey results revealed very high satisfaction with treatment (85%), with the vast majority preferring treatment with upadacitinib to their previous biological therapy. Conclusion In this real-world study, induction therapy with upadacitinib was well tolerated and demonstrated good efficacy with excellent response and remission rates in a mixed patient cohort that included many with highly refractory disease. No unexpected safety signals were seen. The patient experience was overwhelmingly positive. If this data is replicated in larger studies there is an increasingly strong rationale for introducing upadacitinib earlier in the sequencing of advanced therapies.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"120 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559383","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/jjad212.0352
C Soares, J Fiuza, C Rodrigues, J Gil, N Craveiro, P Ministro
Background Morphological and functional cardiac involvement is rarely seen in inflammatory bowel disease (IBD) patients but there is evidence that IBD patients have an increased risk of cardiovascular events despite the lower prevalence of traditional cardiovascular (CV) risk factors when compared to the general population. Our systematic review and meta-analysis examined the relationship between IBD and cardiac function, namely incidence of heart failure (HF) and clinical and subclinical echocardiographic changes. Methods Two medical databases, PubMed and Scopus, were systematically searched up to September 2022 to identify all studies reporting heart failure and/or echocardiographic changes in IBD patients. Results We identified 1287 original papers and included 18 in our qualitative analysis. Through analysis of echocardiographic data, we found subtle systolic and diastolic changes in IBD patients. We also found higher vascular dysfunction with increased aortic stiffness, coronary microvascular dysfunction resulting in worse cardiovascular outcomes. This group had an increased risk for HF hospitalizations compared with general population. We have also performed a meta-analysis with 9 studies which included echocardiographic data. In the IBD population we found reduced E/A ratio (Std. MD -0.51, 95% CI: -1.00 to -0.02, p = 0.04, I2 = 87%, p<0.0001), higher values of E/E’ ratio (Std. MD 1.46, 95% CI: 0.86 to 2.07, p<0.00001, I2 = 80%, p=0.02). We evaluated left ventricular function using longitudinal global strain which was decreased in IBD patients (Std. MD 0.66, 95% CI: 0.48 to 0.84, p<0.00001, I2 = 0%, p= 0.55). Overall IBD patients had increased LA diameter (Std. MD 0.06, 95% CI: 0.12 to 0.24, p = 0.50, I2 = 20%), and an increased LA area (Std. MD 0.03, 95% CI: 0.24 to 0.29, p = 0.85, I2 = 0%), but no statistical significance was not reached. A significant increase in inter-atrial and right intra-atrial conduction delay was observed in IBD patients (Std. MD 0.88, 95% CI: 0.45 to 1.31, p<0.0001, I2 = 42%; Std. MD 0.9, 95% CI: 0.57 to 1.22, p < 0.00001, I2 = 0%, respectively). We found no significant bias in our analysis using CASP checklist. Conclusion There is significant evidence to conclude that the IBD population has increased risk for LV and atrial dysfunction, vascular changes, arrhythmias, and heart failure hospitalization. Screening with sensitive imaging like speckle tracking echocardiography could identify early subclinical changes. IBD is in fact a cardiovascular risk factor and tight inflammation control may reduce the risk.
{"title":"P222 Inflammatory Bowel Disease and cardiac function: a systematic review of literature with meta-analysis","authors":"C Soares, J Fiuza, C Rodrigues, J Gil, N Craveiro, P Ministro","doi":"10.1093/ecco-jcc/jjad212.0352","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0352","url":null,"abstract":"Background Morphological and functional cardiac involvement is rarely seen in inflammatory bowel disease (IBD) patients but there is evidence that IBD patients have an increased risk of cardiovascular events despite the lower prevalence of traditional cardiovascular (CV) risk factors when compared to the general population. Our systematic review and meta-analysis examined the relationship between IBD and cardiac function, namely incidence of heart failure (HF) and clinical and subclinical echocardiographic changes. Methods Two medical databases, PubMed and Scopus, were systematically searched up to September 2022 to identify all studies reporting heart failure and/or echocardiographic changes in IBD patients. Results We identified 1287 original papers and included 18 in our qualitative analysis. Through analysis of echocardiographic data, we found subtle systolic and diastolic changes in IBD patients. We also found higher vascular dysfunction with increased aortic stiffness, coronary microvascular dysfunction resulting in worse cardiovascular outcomes. This group had an increased risk for HF hospitalizations compared with general population. We have also performed a meta-analysis with 9 studies which included echocardiographic data. In the IBD population we found reduced E/A ratio (Std. MD -0.51, 95% CI: -1.00 to -0.02, p = 0.04, I2 = 87%, p&lt;0.0001), higher values of E/E’ ratio (Std. MD 1.46, 95% CI: 0.86 to 2.07, p&lt;0.00001, I2 = 80%, p=0.02). We evaluated left ventricular function using longitudinal global strain which was decreased in IBD patients (Std. MD 0.66, 95% CI: 0.48 to 0.84, p&lt;0.00001, I2 = 0%, p= 0.55). Overall IBD patients had increased LA diameter (Std. MD 0.06, 95% CI: 0.12 to 0.24, p = 0.50, I2 = 20%), and an increased LA area (Std. MD 0.03, 95% CI: 0.24 to 0.29, p = 0.85, I2 = 0%), but no statistical significance was not reached. A significant increase in inter-atrial and right intra-atrial conduction delay was observed in IBD patients (Std. MD 0.88, 95% CI: 0.45 to 1.31, p&lt;0.0001, I2 = 42%; Std. MD 0.9, 95% CI: 0.57 to 1.22, p &lt; 0.00001, I2 = 0%, respectively). We found no significant bias in our analysis using CASP checklist. Conclusion There is significant evidence to conclude that the IBD population has increased risk for LV and atrial dysfunction, vascular changes, arrhythmias, and heart failure hospitalization. Screening with sensitive imaging like speckle tracking echocardiography could identify early subclinical changes. IBD is in fact a cardiovascular risk factor and tight inflammation control may reduce the risk.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559384","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/jjad212.1117
A Giordano, I Pérez Martínez, J P Gisbert, E Ricart, M A M Dolores, F Mesonero, D C P M Luisa, M Rivero, E Iglesias Flores, S Fernández-Prada, M Calafat, M Arroyo Villarino, M Á de Jorge Turrión, E Rodríguez-González, P Corsino Roche, D Carpio, E Brunet, F Rodriguez Moranta, L Arias García, I Pascual, F Bermejo, L Madero, M Esteve, C González Muñoza, P Martínez-Montiel, J M Huguet, J L Pérez Calle, I Rodríguez-Lago, M Sierra Ausín, R H Lorente Poyatos, O García-Bosch, G Surís Marín, C Taxonera, Á Ponferrada-Díaz, M Barreiro-de Acosta, L Bujanda, R Blat Serra, L Ramos, E Domènech, E Garcia Planella
Background Crohn's disease (CD) presents differences in genetics, inflammatory components, and microbiota depending on its location. Therapy efficacy may be linked to disease location, but existing research has yielded conflicting results. This study aims to investigate the impact of CD location on first-line biologic therapy requirement and persistence and the risk of intestinal resections. Methods CD patients included in the prospectively maintained ENEIDA registry between January 2005 and May 2023 were considered for the study. Demographics, disease phenotype and location, complications, the utilization of biologic therapies, and intestinal surgeries were analyzed. Cox proportional hazards and Kaplan-Meier methods were used for the analysis of biologic requirement and persistence and risk of surgery. Results A cohort of 17,508 patients was included, with a median follow-up period of 6 years (IQR 2-10 years). The most common disease locations were ileal (43.3%) and ileocolonic (39%), with lower frequency for colonic (16.4%) and upper-gastrointestinal disease (1.2%). A first biologic was used in 54.5% of patients (n=9,543), with a higher 5-year requirement in ileocolonic disease compared to ileal and colonic disease (60.1% vs 53% vs 49.9%, p<0.001). Ileal disease presented the lowest 5-year persistence rate compared to ileocolonic and colonic location (39% vs 41.6% vs 45.1%, p=0.004). Ileal location (aHR 1.084, 95%CI 1.006-1.167), female sex (adjusted Hazard Ratio [aHR] 1.173, 95%CI 1.096-1.254), extraintestinal manifestations (aHR 1.163, 95%CI 1.080-1.251), a history of abdominal surgery (aHR 1.539, 95%CI 1.426-1.661) were independent predictors of drug discontinuation. The cumulative need for intestinal resections was 25.8% (n=4,512), with ileal disease showing the highest hazard for 5-year surgery compared to ileo-colonic and colonic location (19.5% vs 17.8 vs 8.3%, p<0.001). Ileal disease (aHR 1.194, 95%CI 1.101-1.295), stricturing (aHR 2.575, 95%CI 2.378-2.787) and penetrating phenotypes (aHR 2.485, 95%CI 2.261-2.734), a history of biologic therapy (aHR 1.386, 95%CI 1.262-1.522) and smoking (aHR 1.089, 95%CI 1.004-1.180) were independent predictors of intestinal resections. Survival analysis for biologic requirement, persistence, and the risk of intestinal resections is illustrated in Figure 1. Conclusion Ileal disease is associated with a higher requirement for biologic therapy, showing the poorest persistence. It also demonstrates the highest probability of intestinal resections among CD locations. These findings provide valuable insights into tailoring treatment strategies based on CD location.
背景克罗恩病（CD）因发病部位不同而在遗传学、炎症成分和微生物群方面存在差异。治疗效果可能与患病部位有关，但现有研究得出的结果并不一致。本研究旨在探讨 CD 所在位置对一线生物治疗需求和持续性以及肠切除风险的影响。方法 本研究考虑了 2005 年 1 月至 2023 年 5 月期间纳入前瞻性 ENEIDA 登记的 CD 患者。研究分析了人口统计学、疾病表型和部位、并发症、生物疗法的使用以及肠道手术。采用 Cox 比例危险度法和 Kaplan-Meier 法分析生物制剂需求和持续性以及手术风险。结果 共纳入 17,508 名患者，中位随访时间为 6 年（IQR 2-10 年）。最常见的疾病部位是回肠（43.3%）和回结肠（39%），结肠（16.4%）和上消化道疾病（1.2%）的发病率较低。54.5%的患者（n=9,543）首次使用生物制剂，与回肠和结肠疾病相比，回结肠疾病的5年需求量更高（60.1% vs 53% vs 49.9%，p<0.001）。与回结肠和结肠疾病相比，回肠疾病的 5 年持续率最低（39% vs 41.6% vs 45.1%，p=0.004）。回肠部位（aHR 1.084，95%CI 1.006-1.167）、女性性别（调整后危险比 [aHR] 1.173，95%CI 1.096-1.254）、肠道外表现（aHR 1.163，95%CI 1.080-1.251）、腹部手术史（aHR 1.539，95%CI 1.426-1.661）是停药的独立预测因素。肠切除术的累计需求为 25.8%（n=4,512），与回肠结肠和结肠位置相比，回肠疾病显示出最高的 5 年手术风险（19.5% vs 17.8 vs 8.3%，p<0.001）。回肠疾病（aHR 1.194，95%CI 1.101-1.295）、狭窄（aHR 2.575，95%CI 2.378-2.787）和穿透表型（aHR 2.485，95%CI 2.261-2.734）、生物治疗史（aHR 1.386，95%CI 1.262-1.522）和吸烟（aHR 1.089，95%CI 1.004-1.180）是肠切除的独立预测因素。图 1 显示了生物需求、持续性和肠切除风险的生存分析。结论 回肠疾病对生物制剂治疗的需求较高，显示出最差的持续性。同时，在 CD 病变部位中，回肠切除的概率也最高。这些发现为根据 CD 病变部位制定治疗策略提供了宝贵的见解。
{"title":"P987 Impact of Crohn’s Disease Location on Biologic Therapy Persistence and the Risk of Intestinal Surgery: Insights from the ENEIDA Registry (the DISCOLOC Study)","authors":"A Giordano, I Pérez Martínez, J P Gisbert, E Ricart, M A M Dolores, F Mesonero, D C P M Luisa, M Rivero, E Iglesias Flores, S Fernández-Prada, M Calafat, M Arroyo Villarino, M Á de Jorge Turrión, E Rodríguez-González, P Corsino Roche, D Carpio, E Brunet, F Rodriguez Moranta, L Arias García, I Pascual, F Bermejo, L Madero, M Esteve, C González Muñoza, P Martínez-Montiel, J M Huguet, J L Pérez Calle, I Rodríguez-Lago, M Sierra Ausín, R H Lorente Poyatos, O García-Bosch, G Surís Marín, C Taxonera, Á Ponferrada-Díaz, M Barreiro-de Acosta, L Bujanda, R Blat Serra, L Ramos, E Domènech, E Garcia Planella","doi":"10.1093/ecco-jcc/jjad212.1117","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.1117","url":null,"abstract":"Background Crohn's disease (CD) presents differences in genetics, inflammatory components, and microbiota depending on its location. Therapy efficacy may be linked to disease location, but existing research has yielded conflicting results. This study aims to investigate the impact of CD location on first-line biologic therapy requirement and persistence and the risk of intestinal resections. Methods CD patients included in the prospectively maintained ENEIDA registry between January 2005 and May 2023 were considered for the study. Demographics, disease phenotype and location, complications, the utilization of biologic therapies, and intestinal surgeries were analyzed. Cox proportional hazards and Kaplan-Meier methods were used for the analysis of biologic requirement and persistence and risk of surgery. Results A cohort of 17,508 patients was included, with a median follow-up period of 6 years (IQR 2-10 years). The most common disease locations were ileal (43.3%) and ileocolonic (39%), with lower frequency for colonic (16.4%) and upper-gastrointestinal disease (1.2%). A first biologic was used in 54.5% of patients (n=9,543), with a higher 5-year requirement in ileocolonic disease compared to ileal and colonic disease (60.1% vs 53% vs 49.9%, p&lt;0.001). Ileal disease presented the lowest 5-year persistence rate compared to ileocolonic and colonic location (39% vs 41.6% vs 45.1%, p=0.004). Ileal location (aHR 1.084, 95%CI 1.006-1.167), female sex (adjusted Hazard Ratio [aHR] 1.173, 95%CI 1.096-1.254), extraintestinal manifestations (aHR 1.163, 95%CI 1.080-1.251), a history of abdominal surgery (aHR 1.539, 95%CI 1.426-1.661) were independent predictors of drug discontinuation. The cumulative need for intestinal resections was 25.8% (n=4,512), with ileal disease showing the highest hazard for 5-year surgery compared to ileo-colonic and colonic location (19.5% vs 17.8 vs 8.3%, p&lt;0.001). Ileal disease (aHR 1.194, 95%CI 1.101-1.295), stricturing (aHR 2.575, 95%CI 2.378-2.787) and penetrating phenotypes (aHR 2.485, 95%CI 2.261-2.734), a history of biologic therapy (aHR 1.386, 95%CI 1.262-1.522) and smoking (aHR 1.089, 95%CI 1.004-1.180) were independent predictors of intestinal resections. Survival analysis for biologic requirement, persistence, and the risk of intestinal resections is illustrated in Figure 1. Conclusion Ileal disease is associated with a higher requirement for biologic therapy, showing the poorest persistence. It also demonstrates the highest probability of intestinal resections among CD locations. These findings provide valuable insights into tailoring treatment strategies based on CD location.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559394","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/jjad212.1079
E Fuentes-Valenzuela, I Bastón-Rey, F J García-Alonso, E Leo Carnerero, I Garcia de la Filia, A Pedraza Pérez, R M Sáiz Chumillas, A Pascual Oliver, C Muñoz Villafranca, V Moreno, C Suárez Ferrer, G Molina Arriero, R Ferreiro-Iglesias, P Vega Villaamil, D Gardeazábal Mateos, J X Segarra-Ortega, A Garrido Marín, A I Doallo, A Elosua, H Alonso-Galán, E Brunet- Mas, N Jimenez García, F López Romero-Salazar, B Velayos, L Carballo-Folgoso, C Pérez Santamaría, L Mata Román, A Núñez Ortiz, J Barrio, M Barreiro-de Acosta, A Gutiérrez-Casbas
Background Few small studies have assessed the efficacy of topical therapy with tacrolimus in patients with ulcerative colitis (UC). The aim of our study was to evaluate its effectiveness and safety in a real-world setting. Methods A multicenter observational retrospective study at 25 Spanish GETECCU hospitals was performed. Adult patients with UC who received topical tacrolimus from January 2009 to January 2023 were eligible. Inclusion criteria were proctitis, left-sided, or extensive colitis with persistent distal colonic activity confirmed endoscopically during the previous 3 months. Clinical and biochemical data were collected at baseline, week 4, 8 and 54. Tacrolimus trough levels were evaluated in week 4 and 8. Primary outcome was clinical response at week 8, defined as a ≥3 points or ≥30% decrease of partial Mayo score with ≥1point reduction in the bleeding score. Mean partial mayo scores were compared using the t-test. A p<0.05 was considered statistically significant. Results 106 patients, 59 (55.6%) males, median age 48.7 years (IQR:39.9-59.7), received rectal tacrolimus during a median of 9.7 weeks (IQR:5-18.7). Sixty-four patients (60.4%) received suppositories, 41 (38.7%) enemas and 1 patient an ointment (0.9%). Thirty (28.3%) were patients with proctitis, 45 (42.4%) with left colitis and 31 (29.2%) with extensive colitis. At baseline, 54 patients (50.9%) received concomitant biological/small molecules therapy, while 14 patients received immunomodulators. Most common dose was 2 mg (84%) Q24H (71.7%). A significant decrease in mean partial mayo score was observed at week 4 and 8 (figure 1). Clinical response at week 8 was achieved in 63 patients (66.3%) and clinical remission in 42 (44.2%). 32 patients (33.7%) were non-responder at week 8. Clinical response and remission at week 4 were achieved in 56 (57.7%) and 33 (34.4%), respectively. Clinical response at week 8 was similar between the group with concomitant biological therapy and without (64.6.9% vs 68.1%, p=0.8). Clinical response at week 8 was similar among different extensions (proctitis: 55.6%; left colitis: 80%; extensive colitis 57.1%; p=0.052). Clinical outcomes are detailed in table 1. Median tacrolimus trough levels at week 4 was 3.4 ng/ml (IQR 1.5-6.7) and 2.9 ng/ml (IQR 1.5-6) at week 8. Adverse events were detected in 21 patients (19.8%), Thirteen were graded as mild and 8 moderate. Treatment was ceased due to adverse events in 11 (10.4%) patients. Conclusion Topical tacrolimus is effective in UC achieving clinical response in more than sixty percent at week 8 with even lower doses than reported in clinical trials. Adverse events reported in nearly 20% of patients were mostly mild.
{"title":"P949 Effectiveness and safety of rectal tacrolimus in patients with ulcerative colitis. TACRO-TOPIC study. A multicenter study from the young group of GETECCU","authors":"E Fuentes-Valenzuela, I Bastón-Rey, F J García-Alonso, E Leo Carnerero, I Garcia de la Filia, A Pedraza Pérez, R M Sáiz Chumillas, A Pascual Oliver, C Muñoz Villafranca, V Moreno, C Suárez Ferrer, G Molina Arriero, R Ferreiro-Iglesias, P Vega Villaamil, D Gardeazábal Mateos, J X Segarra-Ortega, A Garrido Marín, A I Doallo, A Elosua, H Alonso-Galán, E Brunet- Mas, N Jimenez García, F López Romero-Salazar, B Velayos, L Carballo-Folgoso, C Pérez Santamaría, L Mata Román, A Núñez Ortiz, J Barrio, M Barreiro-de Acosta, A Gutiérrez-Casbas","doi":"10.1093/ecco-jcc/jjad212.1079","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.1079","url":null,"abstract":"Background Few small studies have assessed the efficacy of topical therapy with tacrolimus in patients with ulcerative colitis (UC). The aim of our study was to evaluate its effectiveness and safety in a real-world setting. Methods A multicenter observational retrospective study at 25 Spanish GETECCU hospitals was performed. Adult patients with UC who received topical tacrolimus from January 2009 to January 2023 were eligible. Inclusion criteria were proctitis, left-sided, or extensive colitis with persistent distal colonic activity confirmed endoscopically during the previous 3 months. Clinical and biochemical data were collected at baseline, week 4, 8 and 54. Tacrolimus trough levels were evaluated in week 4 and 8. Primary outcome was clinical response at week 8, defined as a ≥3 points or ≥30% decrease of partial Mayo score with ≥1point reduction in the bleeding score. Mean partial mayo scores were compared using the t-test. A p&lt;0.05 was considered statistically significant. Results 106 patients, 59 (55.6%) males, median age 48.7 years (IQR:39.9-59.7), received rectal tacrolimus during a median of 9.7 weeks (IQR:5-18.7). Sixty-four patients (60.4%) received suppositories, 41 (38.7%) enemas and 1 patient an ointment (0.9%). Thirty (28.3%) were patients with proctitis, 45 (42.4%) with left colitis and 31 (29.2%) with extensive colitis. At baseline, 54 patients (50.9%) received concomitant biological/small molecules therapy, while 14 patients received immunomodulators. Most common dose was 2 mg (84%) Q24H (71.7%). A significant decrease in mean partial mayo score was observed at week 4 and 8 (figure 1). Clinical response at week 8 was achieved in 63 patients (66.3%) and clinical remission in 42 (44.2%). 32 patients (33.7%) were non-responder at week 8. Clinical response and remission at week 4 were achieved in 56 (57.7%) and 33 (34.4%), respectively. Clinical response at week 8 was similar between the group with concomitant biological therapy and without (64.6.9% vs 68.1%, p=0.8). Clinical response at week 8 was similar among different extensions (proctitis: 55.6%; left colitis: 80%; extensive colitis 57.1%; p=0.052). Clinical outcomes are detailed in table 1. Median tacrolimus trough levels at week 4 was 3.4 ng/ml (IQR 1.5-6.7) and 2.9 ng/ml (IQR 1.5-6) at week 8. Adverse events were detected in 21 patients (19.8%), Thirteen were graded as mild and 8 moderate. Treatment was ceased due to adverse events in 11 (10.4%) patients. Conclusion Topical tacrolimus is effective in UC achieving clinical response in more than sixty percent at week 8 with even lower doses than reported in clinical trials. Adverse events reported in nearly 20% of patients were mostly mild.","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":"139559422","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/jjad212.0648
A Jatkowska, B White, I Campbell, E Brownson, B Short, J Clowe, J P Seenan, D R Gaya, S Din, G T Ho, E Robertson, C Mowat, S Milling, J MacDonald, K Gerasimidis
Background Biologics, such as anti-TNFα agents, are commonly used in the management of Crohn’s disease (CD). A significant proportion of patients do not respond to treatment, necessitating the exploration of pre-treatment predictors of treatment response. Methods Anti-TNFα-naïve adults with active CD (Crohn’s Disease Activity Index; CDAI≥150) participating in an RCT (NCT04859088) were randomised to receive adalimumab monotherapy or adalimumab combination therapy with 50% partial enteral nutrition (PEN). Treatment response (CDAI<150) was assessed after 6 weeks, baseline diet was assessed with EPIC-Norfolk FFQ, alternative Mediterranean diet scores (aMED), and principal component analysis (PCA) with orthogonal (varimax) rotation was used to identify data-derived dietary patterns. Baseline predictors evaluated included PEN use, steroid use, immunomodulator use, age, disease duration, CDAI, C-Reactive protein (CRP), albumin, haemoglobin, Scottish Index of Multiple Deprivation (SIMD) score, adherence to dietary patterns identified, aMED score, smoking status, alcohol consumption, physical activity level, body mass index (BMI), fat mass (kg/m2), fat-free mass (kg/m2), and handgrip strength. Differential analysis between responders and non-responders was carried out with general linear model or chi-square test when appropriate. Random forest model with recursive feature elimination (RF-RFE) was used to identify the most predictive factors of treatment response. Results Of 42 participants recruited to the study, 62% (26) responded to treatment. PCA revealed four dietary patterns (Figure 1A). Responders to adalimumab were younger (mean (SD): 36.0 (17.1) vs 50.8 (10.0), P=0.004), had lower baseline CDAI (mean (SD): 228 (62) vs 286 (78), P=0.018), higher CRP (14.5 (19.2) vs 4.6 (5.8) mg/L, P=0.036), were less likely to smoke (31% (5 of 16) vs 8% (2 of 26), and less likely to adhere to a dietary pattern characterised by high consumption of animal products (PC2) (P=0.030). Adherence to PC2 also correlated positively with age (r=0.327, P=0.035). The RF-RFE algorithm highlighted young age, low baseline CDAI and low PC2 adherence as key factors (Sensitivity: 77%, Specificity: 63%, PPV: 77%, NPV: 63%, OOB: 29%, P=0.012) (Figure 1B). Interestingly, exclusion of dietary factors improved diagnostic performance of the model (Sensitivity: 77%, Specificity: 75%, PPV: 83%, NPV: 67%, OOB: 24%, P=0.003) (Figure 1C), indicating potential interactions by other factors like age. Conclusion Young age, non-smoking, low baseline CDAI and elevated CRP predict adalimumab response in anti-TNFα-naïve adults. While dietary factors may also play a role, their impact seems confounded by other non-dietary factors. Further research is warranted in this area.
{"title":"P518 Dietary and non-dietary predictors of treatment response to adalimumab in anti-TNFα-naïve adults with Crohn’s disease","authors":"A Jatkowska, B White, I Campbell, E Brownson, B Short, J Clowe, J P Seenan, D R Gaya, S Din, G T Ho, E Robertson, C Mowat, S Milling, J MacDonald, K Gerasimidis","doi":"10.1093/ecco-jcc/jjad212.0648","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0648","url":null,"abstract":"Background Biologics, such as anti-TNFα agents, are commonly used in the management of Crohn’s disease (CD). A significant proportion of patients do not respond to treatment, necessitating the exploration of pre-treatment predictors of treatment response. Methods Anti-TNFα-naïve adults with active CD (Crohn’s Disease Activity Index; CDAI≥150) participating in an RCT (NCT04859088) were randomised to receive adalimumab monotherapy or adalimumab combination therapy with 50% partial enteral nutrition (PEN). Treatment response (CDAI&lt;150) was assessed after 6 weeks, baseline diet was assessed with EPIC-Norfolk FFQ, alternative Mediterranean diet scores (aMED), and principal component analysis (PCA) with orthogonal (varimax) rotation was used to identify data-derived dietary patterns. Baseline predictors evaluated included PEN use, steroid use, immunomodulator use, age, disease duration, CDAI, C-Reactive protein (CRP), albumin, haemoglobin, Scottish Index of Multiple Deprivation (SIMD) score, adherence to dietary patterns identified, aMED score, smoking status, alcohol consumption, physical activity level, body mass index (BMI), fat mass (kg/m2), fat-free mass (kg/m2), and handgrip strength. Differential analysis between responders and non-responders was carried out with general linear model or chi-square test when appropriate. Random forest model with recursive feature elimination (RF-RFE) was used to identify the most predictive factors of treatment response. Results Of 42 participants recruited to the study, 62% (26) responded to treatment. PCA revealed four dietary patterns (Figure 1A). Responders to adalimumab were younger (mean (SD): 36.0 (17.1) vs 50.8 (10.0), P=0.004), had lower baseline CDAI (mean (SD): 228 (62) vs 286 (78), P=0.018), higher CRP (14.5 (19.2) vs 4.6 (5.8) mg/L, P=0.036), were less likely to smoke (31% (5 of 16) vs 8% (2 of 26), and less likely to adhere to a dietary pattern characterised by high consumption of animal products (PC2) (P=0.030). Adherence to PC2 also correlated positively with age (r=0.327, P=0.035). The RF-RFE algorithm highlighted young age, low baseline CDAI and low PC2 adherence as key factors (Sensitivity: 77%, Specificity: 63%, PPV: 77%, NPV: 63%, OOB: 29%, P=0.012) (Figure 1B). Interestingly, exclusion of dietary factors improved diagnostic performance of the model (Sensitivity: 77%, Specificity: 75%, PPV: 83%, NPV: 67%, OOB: 24%, P=0.003) (Figure 1C), indicating potential interactions by other factors like age. Conclusion Young age, non-smoking, low baseline CDAI and elevated CRP predict adalimumab response in anti-TNFα-naïve adults. While dietary factors may also play a role, their impact seems confounded by other non-dietary factors. Further research is warranted in this area.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":"88 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559424","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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