Pub Date : 2024-01-27DOI: 10.1093/ecco-jcc/jjad125
Bénédicte Caron, Vipul Jairath, Valérie Laurent, Jaap Stoker, Andrea Laghi, Geert R D'Haens, Silvio Danese, Laurent Peyrin-Biroulet
Background: Magnetic resonance imaging is increasingly used to assess treatment response in Crohn's disease clinical trials. We aimed to describe the definition of MRI response and remission as assessed by magnetic resonance enterography [MRE] to evaluate treatment efficacy in these patients.
Methods: Electronic databases were searched up to May 1, 2023. All published studies enrolling patients with inflammatory bowel disease and assessment of treatment efficacy with MRE were eligible for inclusion.
Results: Eighteen studies were included. All studies were performed in patients with Crohn's disease. The study period ranged from 2008 to 2023. The majority of studies used endoscopy as the reference standard [61.1%]. MRE response was defined in 11 studies [61.1%]. Five scores and nine different definitions were proposed for MRE response. MRE remission was defined in 12 studies [66.7%]. Three scores and nine different definitions for MRE remission were described. The MaRIA score was the most frequent index used to evaluate MRE response [63.6%] and remission [41.7%]. MRE response was defined as MaRIA score <11 in 63.6% of studies using this index. In 60% of studies using the MaRIA score, MRE remission was defined as MaRIA score <7. In addition, 11 different time points of assessment were reported, ranging from 6 weeks to years.
Conclusion: In this systematic review, significant heterogeneity in the definition of MRE response and remission evaluated in patients with Crohn's disease was observed. Harmonization of eligibility and outcome criteria for MRE in Crohn's Disease clinical trials is needed.
{"title":"Defining Magnetic Resonance Imaging Treatment Response and Remission in Crohn's Disease: A Systematic Review.","authors":"Bénédicte Caron, Vipul Jairath, Valérie Laurent, Jaap Stoker, Andrea Laghi, Geert R D'Haens, Silvio Danese, Laurent Peyrin-Biroulet","doi":"10.1093/ecco-jcc/jjad125","DOIUrl":"10.1093/ecco-jcc/jjad125","url":null,"abstract":"<p><strong>Background: </strong>Magnetic resonance imaging is increasingly used to assess treatment response in Crohn's disease clinical trials. We aimed to describe the definition of MRI response and remission as assessed by magnetic resonance enterography [MRE] to evaluate treatment efficacy in these patients.</p><p><strong>Methods: </strong>Electronic databases were searched up to May 1, 2023. All published studies enrolling patients with inflammatory bowel disease and assessment of treatment efficacy with MRE were eligible for inclusion.</p><p><strong>Results: </strong>Eighteen studies were included. All studies were performed in patients with Crohn's disease. The study period ranged from 2008 to 2023. The majority of studies used endoscopy as the reference standard [61.1%]. MRE response was defined in 11 studies [61.1%]. Five scores and nine different definitions were proposed for MRE response. MRE remission was defined in 12 studies [66.7%]. Three scores and nine different definitions for MRE remission were described. The MaRIA score was the most frequent index used to evaluate MRE response [63.6%] and remission [41.7%]. MRE response was defined as MaRIA score <11 in 63.6% of studies using this index. In 60% of studies using the MaRIA score, MRE remission was defined as MaRIA score <7. In addition, 11 different time points of assessment were reported, ranging from 6 weeks to years.</p><p><strong>Conclusion: </strong>In this systematic review, significant heterogeneity in the definition of MRE response and remission evaluated in patients with Crohn's disease was observed. Harmonization of eligibility and outcome criteria for MRE in Crohn's Disease clinical trials is needed.</p>","PeriodicalId":15547,"journal":{"name":"Journal of Crohns & Colitis","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10274647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-27DOI: 10.1093/ecco-jcc/jjad121
Ohad Atia, Chagit Friss, Gili Focht, Ramit Magen Rimon, Natan Ledderman, Shira Greenfeld, Amir Ben-Tov, Yiska Loewenberg Weisband, Eran Matz, Yuri Gorelik, Yehuda Chowers, Iris Dotan, Dan Turner
Background: In this nationwide study we aimed to compare the durability of the first initiated biologic in Crohn's disease [CD], stratified by monotherapy and combotherapy.
Methods: We used data from the epi-IIRN cohort, which includes 98% of the Israeli inflammatory bowel disease population [2005-2020]. Durability was defined as consistent treatment without surgery or added medications [except for combination therapy with thiopurines or methotrexate]. All comparisons were based on stringent propensity-score matching and paired time-to-event analyses.
Results: A total of 19 264 patients with CD were included, of whom 7452 [39%] received biologics with a median follow-up of 6.8 years (interquartile range [IQR] 3.6-10.7). Time to biologics decreased gradually from 6.7 years [IQR 2.7-10.4] in 2005 to 0.2 years [0.07-0.23] in 2020. The durability of the first biologic after 1 and 3 years was higher with adalimumab monotherapy [88%/61%] than vedolizumab monotherapy [81%/59%; n = 394 matched patients, p = 0.04] and similar between infliximab monotherapy and vedolizumab monotherapy [65%/43%; n = 182 matched patients, p = 0.1]. Durability was higher in adalimumab monotherapy vs infliximab monotherapy [83%/62% vs 71%/48% at 1/3 years; p <0.001] and it was similar in adalimumab monotherapy vs infliximab combotherapy [87%/63% vs 80%/58%, respectively; p = 0.1]. Durability was higher in combotherapy compared with monotherapy for both infliximab [85%/64% vs 67%/43%, respectively; n = 496 matched pairs, p <0.001], and adalimumab [93%/76% vs 82%/62%, respectively; n = 540 matched pairs, p <0.001].
Conclusion: Durability of the first biologic in CD was highest for adalimumab monotherapy. Combotherapy further increased the durability of adalimumab and infliximab. Unless otherwise indicated, our data may support using anti-tumour necrosis factors [TNFs] as first-line biologics in CD, particularly adalimumab if monotherapy is advised.
{"title":"Durability of the First Biologic in Patients with Crohn's Disease: A Nationwide Study from the epi-IIRN.","authors":"Ohad Atia, Chagit Friss, Gili Focht, Ramit Magen Rimon, Natan Ledderman, Shira Greenfeld, Amir Ben-Tov, Yiska Loewenberg Weisband, Eran Matz, Yuri Gorelik, Yehuda Chowers, Iris Dotan, Dan Turner","doi":"10.1093/ecco-jcc/jjad121","DOIUrl":"10.1093/ecco-jcc/jjad121","url":null,"abstract":"<p><strong>Background: </strong>In this nationwide study we aimed to compare the durability of the first initiated biologic in Crohn's disease [CD], stratified by monotherapy and combotherapy.</p><p><strong>Methods: </strong>We used data from the epi-IIRN cohort, which includes 98% of the Israeli inflammatory bowel disease population [2005-2020]. Durability was defined as consistent treatment without surgery or added medications [except for combination therapy with thiopurines or methotrexate]. All comparisons were based on stringent propensity-score matching and paired time-to-event analyses.</p><p><strong>Results: </strong>A total of 19 264 patients with CD were included, of whom 7452 [39%] received biologics with a median follow-up of 6.8 years (interquartile range [IQR] 3.6-10.7). Time to biologics decreased gradually from 6.7 years [IQR 2.7-10.4] in 2005 to 0.2 years [0.07-0.23] in 2020. The durability of the first biologic after 1 and 3 years was higher with adalimumab monotherapy [88%/61%] than vedolizumab monotherapy [81%/59%; n = 394 matched patients, p = 0.04] and similar between infliximab monotherapy and vedolizumab monotherapy [65%/43%; n = 182 matched patients, p = 0.1]. Durability was higher in adalimumab monotherapy vs infliximab monotherapy [83%/62% vs 71%/48% at 1/3 years; p <0.001] and it was similar in adalimumab monotherapy vs infliximab combotherapy [87%/63% vs 80%/58%, respectively; p = 0.1]. Durability was higher in combotherapy compared with monotherapy for both infliximab [85%/64% vs 67%/43%, respectively; n = 496 matched pairs, p <0.001], and adalimumab [93%/76% vs 82%/62%, respectively; n = 540 matched pairs, p <0.001].</p><p><strong>Conclusion: </strong>Durability of the first biologic in CD was highest for adalimumab monotherapy. Combotherapy further increased the durability of adalimumab and infliximab. Unless otherwise indicated, our data may support using anti-tumour necrosis factors [TNFs] as first-line biologics in CD, particularly adalimumab if monotherapy is advised.</p>","PeriodicalId":15547,"journal":{"name":"Journal of Crohns & Colitis","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9822504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-27DOI: 10.1093/ecco-jcc/jjad126
Jakub Hurych, Anna Mascellani Bergo, Tereza Lerchova, Lucie Hlinakova, Michal Kubat, Hana Malcova, Dita Cebecauerova, Jan Schwarz, Eva Karaskova, Tomas Hecht, Radim Vyhnanek, Lenka Toukalkova, Vojtech Dotlacil, Katerina Greinerova, Anabela Cizkova, Rudolf Horvath, Jiri Bronsky, Jaroslav Havlik, Ondrej Hradsky, Ondrej Cinek
Background and aims: Treatment with anti-tumour necrosis factor α antibodies [anti-TNF] changes the dysbiotic faecal bacteriome in Crohn's disease [CD]. However, it is not known whether these changes are due to decreasing mucosal inflammatory activity or whether similar bacteriome reactions might be observed in gut-healthy subjects. Therefore, we explored changes in the faecal bacteriome and metabolome upon anti-TNF administration [and therapeutic response] in children with CD and contrasted those to anti-TNF-treated children with juvenile idiopathic arthritis [JIA].
Methods: Faecal samples collected longitudinally before and during anti-TNF therapy were analysed with regard to the bacteriome by massively parallel sequencing of the 16S rDNA [V4 region] and the faecal metabolome by 1H nuclear magnetic resonance imaging. The response to treatment by mucosal healing was assessed by the MINI index at 3 months after the treatment started. We also tested several representative gut bacterial strains for in vitro growth inhibition by infliximab.
Results: We analysed 530 stool samples from 121 children [CD 54, JIA 18, healthy 49]. Bacterial community composition changed on anti-TNF in CD: three members of the class Clostridia increased on anti-TNF, whereas the class Bacteroidia decreased. Among faecal metabolites, glucose and glycerol increased, whereas isoleucine and uracil decreased. Some of these changes differed by treatment response [mucosal healing] after anti-TNF. No significant changes in the bacteriome or metabolome were noted upon anti-TNF in JIA. Bacterial growth was not affected by infliximab in a disc diffusion test.
Conclusions: Our findings suggest that gut mucosal healing is responsible for the bacteriome and metabolome changes observed in CD, rather than any general effect of anti-TNF.
背景和目的:使用抗肿瘤坏死因子α抗体[anti-TNF]治疗可改变克罗恩病[CD]患者粪便菌群失调的情况。然而,这些变化是否是由于粘膜炎症活动减少所致,或者在肠道健康的受试者中是否也可能观察到类似的细菌群反应,目前尚不清楚。因此,我们探讨了 CD 儿童服用抗肿瘤坏死因子后粪便细菌组和代谢组的变化[及治疗反应],并将其与服用抗肿瘤坏死因子的幼年特发性关节炎[JIA]儿童进行对比:方法:通过16S rDNA[V4区]大规模平行测序分析细菌组,通过1H核磁共振成像分析粪便代谢组。治疗开始 3 个月后,通过 MINI 指数评估了粘膜愈合对治疗的反应。我们还测试了英夫利昔单抗对几种代表性肠道细菌菌株体外生长的抑制作用:我们分析了 121 名儿童(CD 54 名,JIA 18 名,健康 49 名)的 530 份粪便样本。抗肿瘤坏死因子会改变 CD 患者的细菌群落组成:抗肿瘤坏死因子会增加梭状芽孢杆菌中的三个成员,而类杆菌则会减少。在粪便代谢物中,葡萄糖和甘油增加,而异亮氨酸和尿嘧啶减少。其中一些变化因抗 TNF 后的治疗反应[粘膜愈合]而不同。在 JIA 抗肿瘤坏死因子治疗后,细菌组或代谢组没有发生明显变化。在盘扩散试验中,英夫利西单抗对细菌生长没有影响:我们的研究结果表明,在 CD 中观察到的细菌组和代谢组变化是肠道粘膜愈合造成的,而不是抗肿瘤坏死因子的普遍影响。
{"title":"Faecal Bacteriome and Metabolome Profiles Associated with Decreased Mucosal Inflammatory Activity Upon Anti-TNF Therapy in Paediatric Crohn's Disease.","authors":"Jakub Hurych, Anna Mascellani Bergo, Tereza Lerchova, Lucie Hlinakova, Michal Kubat, Hana Malcova, Dita Cebecauerova, Jan Schwarz, Eva Karaskova, Tomas Hecht, Radim Vyhnanek, Lenka Toukalkova, Vojtech Dotlacil, Katerina Greinerova, Anabela Cizkova, Rudolf Horvath, Jiri Bronsky, Jaroslav Havlik, Ondrej Hradsky, Ondrej Cinek","doi":"10.1093/ecco-jcc/jjad126","DOIUrl":"10.1093/ecco-jcc/jjad126","url":null,"abstract":"<p><strong>Background and aims: </strong>Treatment with anti-tumour necrosis factor α antibodies [anti-TNF] changes the dysbiotic faecal bacteriome in Crohn's disease [CD]. However, it is not known whether these changes are due to decreasing mucosal inflammatory activity or whether similar bacteriome reactions might be observed in gut-healthy subjects. Therefore, we explored changes in the faecal bacteriome and metabolome upon anti-TNF administration [and therapeutic response] in children with CD and contrasted those to anti-TNF-treated children with juvenile idiopathic arthritis [JIA].</p><p><strong>Methods: </strong>Faecal samples collected longitudinally before and during anti-TNF therapy were analysed with regard to the bacteriome by massively parallel sequencing of the 16S rDNA [V4 region] and the faecal metabolome by 1H nuclear magnetic resonance imaging. The response to treatment by mucosal healing was assessed by the MINI index at 3 months after the treatment started. We also tested several representative gut bacterial strains for in vitro growth inhibition by infliximab.</p><p><strong>Results: </strong>We analysed 530 stool samples from 121 children [CD 54, JIA 18, healthy 49]. Bacterial community composition changed on anti-TNF in CD: three members of the class Clostridia increased on anti-TNF, whereas the class Bacteroidia decreased. Among faecal metabolites, glucose and glycerol increased, whereas isoleucine and uracil decreased. Some of these changes differed by treatment response [mucosal healing] after anti-TNF. No significant changes in the bacteriome or metabolome were noted upon anti-TNF in JIA. Bacterial growth was not affected by infliximab in a disc diffusion test.</p><p><strong>Conclusions: </strong>Our findings suggest that gut mucosal healing is responsible for the bacteriome and metabolome changes observed in CD, rather than any general effect of anti-TNF.</p>","PeriodicalId":15547,"journal":{"name":"Journal of Crohns & Colitis","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10821711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9917178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-27DOI: 10.1093/ecco-jcc/jjad134
Walter Reinisch, Vivek Pradhan, Saira Ahmad, Zhen Zhang, Jeremy D Gale
Objective: Central reading of endoscopy is advocated by regulatory agencies for clinical trials in ulcerative colitis [UC]. It is uncertain whether the local/site reader should be included in the reading paradigm. We explore whether using locally- and centrally-determined endoscopic Mayo subscores [eMS] provide a reliable final assessment and whether the paradigm used has an impact on effect size.
Methods: eMS data from the TURANDOT [NCT01620255] study were used to retrospectively examine seven different reading paradigms (using the scores of local readers [LR], first central readers [CR1], second central readers [CR2], and various consensus reads [ConCR]) by assessing inter-rater reliabilities and their impact on the key study endpoint, endoscopic improvement.
Results: More than 40% of eMS scores between two trained central readers were discordant. Central readers had wide variability in scorings at baseline (intraclass correlation coefficient [ICC] of 0.475 [0.339, 0.610] for CR1 vs CR2). Centrally-read scores had variable concordance with LR (LR vs CR1 ICC 0.682 [0.575, 0.788], and LR vs CR2 ICC 0.526 [0.399, 0.653]). Reading paradigms with LR and CR which included a consensus, enhanced ICC estimates to >0.8. At Week 12, without the consensus reads, the CR1 vs CR2 ICC estimates were 0.775 [0.710, 0.841], and with consensus reads the ICC estimates were >0.9. Consensus-based approaches were most favourable to detect a treatment difference.
Conclusion: The ICC between the eMS of two trained and experienced central readers is unexpectedly low, which reinforces that currently used central reading processes are still associated with several weaknesses.
{"title":"Alternative Endoscopy Reading Paradigms Determine Score Reliability and Effect Size in Ulcerative Colitis.","authors":"Walter Reinisch, Vivek Pradhan, Saira Ahmad, Zhen Zhang, Jeremy D Gale","doi":"10.1093/ecco-jcc/jjad134","DOIUrl":"10.1093/ecco-jcc/jjad134","url":null,"abstract":"<p><strong>Objective: </strong>Central reading of endoscopy is advocated by regulatory agencies for clinical trials in ulcerative colitis [UC]. It is uncertain whether the local/site reader should be included in the reading paradigm. We explore whether using locally- and centrally-determined endoscopic Mayo subscores [eMS] provide a reliable final assessment and whether the paradigm used has an impact on effect size.</p><p><strong>Methods: </strong>eMS data from the TURANDOT [NCT01620255] study were used to retrospectively examine seven different reading paradigms (using the scores of local readers [LR], first central readers [CR1], second central readers [CR2], and various consensus reads [ConCR]) by assessing inter-rater reliabilities and their impact on the key study endpoint, endoscopic improvement.</p><p><strong>Results: </strong>More than 40% of eMS scores between two trained central readers were discordant. Central readers had wide variability in scorings at baseline (intraclass correlation coefficient [ICC] of 0.475 [0.339, 0.610] for CR1 vs CR2). Centrally-read scores had variable concordance with LR (LR vs CR1 ICC 0.682 [0.575, 0.788], and LR vs CR2 ICC 0.526 [0.399, 0.653]). Reading paradigms with LR and CR which included a consensus, enhanced ICC estimates to >0.8. At Week 12, without the consensus reads, the CR1 vs CR2 ICC estimates were 0.775 [0.710, 0.841], and with consensus reads the ICC estimates were >0.9. Consensus-based approaches were most favourable to detect a treatment difference.</p><p><strong>Conclusion: </strong>The ICC between the eMS of two trained and experienced central readers is unexpectedly low, which reinforces that currently used central reading processes are still associated with several weaknesses.</p>","PeriodicalId":15547,"journal":{"name":"Journal of Crohns & Colitis","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10821708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10061509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-27DOI: 10.1093/ecco-jcc/jjad130
Stefan Schreiber, Silvio Danese, Axel Dignass, Eugeni Domènech, Massimo C Fantini, Marc Ferrante, Jonas Halfvarson, Ailsa Hart, Fernando Magro, Charlie W Lees, Salvo Leone, Marieke J Pierik, Michele Peters, Polly Field, Helen Fishpool, Laurent Peyrin-Biroulet
Background and aims: Treatment of ulcerative colitis [UC] requires a patient-centric definition of comprehensive disease control that considers improvements in aspects not typically captured by classical landmark trial endpoints. In an international initiative, we reviewed aspects of UC that affect patients and/or indicate mucosal inflammation, to achieve consensus on which aspects to combine in a definition of comprehensive disease control, using a modified Delphi process.
Methods: The Delphi panel comprised 12 gastroenterologists and one patient advocate. Two gastroenterologists were elected as chairs and did not vote. To inform statements, we asked 18 patients and the panel members about their experiences of remission and reviewed published literature. Panel members voted on statements anonymously in three rounds, with a live discussion before Round 3. Consensus was met if ≥67% of the panel agreed. Statements without consensus in Rounds 1 and 2 were revised or discarded after Round 3.
Results: The panel agreed to measure individual patient benefit using a definition of comprehensive disease control that combines aspects currently measured in trials [rectal bleeding, stool frequency, disease-related quality of life, endoscopy, histological inflammatory activity, inflammatory biomarkers, and corticosteroid use] with additional patient-reported symptoms [bowel urgency, abdominal pain, extraintestinal manifestations, fatigue, and sleep disturbance]. The panel agreed on scoring systems and thresholds for many aspects.
Conclusions: Using a robust methodology, we defined comprehensive disease control in UC. Next, we will combine the measurement and scoring of these aspects into a multicomponent tool and will adopt comprehensive disease control as a treatment target in clinical practice and trials.
{"title":"Defining Comprehensive Disease Control for Use as a Treatment Target for Ulcerative Colitis in Clinical Practice: International Delphi Consensus Recommendations.","authors":"Stefan Schreiber, Silvio Danese, Axel Dignass, Eugeni Domènech, Massimo C Fantini, Marc Ferrante, Jonas Halfvarson, Ailsa Hart, Fernando Magro, Charlie W Lees, Salvo Leone, Marieke J Pierik, Michele Peters, Polly Field, Helen Fishpool, Laurent Peyrin-Biroulet","doi":"10.1093/ecco-jcc/jjad130","DOIUrl":"10.1093/ecco-jcc/jjad130","url":null,"abstract":"<p><strong>Background and aims: </strong>Treatment of ulcerative colitis [UC] requires a patient-centric definition of comprehensive disease control that considers improvements in aspects not typically captured by classical landmark trial endpoints. In an international initiative, we reviewed aspects of UC that affect patients and/or indicate mucosal inflammation, to achieve consensus on which aspects to combine in a definition of comprehensive disease control, using a modified Delphi process.</p><p><strong>Methods: </strong>The Delphi panel comprised 12 gastroenterologists and one patient advocate. Two gastroenterologists were elected as chairs and did not vote. To inform statements, we asked 18 patients and the panel members about their experiences of remission and reviewed published literature. Panel members voted on statements anonymously in three rounds, with a live discussion before Round 3. Consensus was met if ≥67% of the panel agreed. Statements without consensus in Rounds 1 and 2 were revised or discarded after Round 3.</p><p><strong>Results: </strong>The panel agreed to measure individual patient benefit using a definition of comprehensive disease control that combines aspects currently measured in trials [rectal bleeding, stool frequency, disease-related quality of life, endoscopy, histological inflammatory activity, inflammatory biomarkers, and corticosteroid use] with additional patient-reported symptoms [bowel urgency, abdominal pain, extraintestinal manifestations, fatigue, and sleep disturbance]. The panel agreed on scoring systems and thresholds for many aspects.</p><p><strong>Conclusions: </strong>Using a robust methodology, we defined comprehensive disease control in UC. Next, we will combine the measurement and scoring of these aspects into a multicomponent tool and will adopt comprehensive disease control as a treatment target in clinical practice and trials.</p>","PeriodicalId":15547,"journal":{"name":"Journal of Crohns & Colitis","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10821705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10004957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-27DOI: 10.1093/ecco-jcc/jjad127
Kwangwoo Kim, Shin Ju Oh, Junho Lee, Ayeong Kwon, Chae-Yeon Yu, Sangsoo Kim, Chang Hwan Choi, Sang-Bum Kang, Tae Oh Kim, Dong Il Park, Chang Kyun Lee
Background and aims: Crohn's disease [CD] has a complex polygenic aetiology with high heritability. There is ongoing effort to identify novel variants associated with susceptibility to CD through a genome-wide association study [GWAS] in large Korean populations.
Methods: Genome-wide variant data from 902 Korean patients with CD and 72 179 controls were used to assess the genetic associations in a meta-analysis with previous Korean GWAS results from 1621 patients with CD and 4419 controls. Epistatic interactions between CD-risk variants of interest were tested using a multivariate logistic regression model with an interaction term.
Results: We identified two novel genetic associations with the risk of CD near ZBTB38 and within the leukocyte immunoglobulin-like receptor [LILR] gene cluster [p < 5 × 10-8], with highly consistent effect sizes between the two independent Korean cohorts. CD-risk variants in the LILR locus are known quantitative trait loci [QTL] for multiple LILR genes, of which LILRB2 directly interacts with various ligands including MHC class I molecules. The LILR lead variant exhibited a significant epistatic interaction with CD-associated regulatory variants for TAP2 involved in the antigen presentation of MHC class I molecules [p = 4.11 × 10-4], showing higher CD-risk effects of the TAP2 variant in individuals carrying more risk alleles of the LILR lead variant (odds ratio [OR] = 0.941, p = 0.686 in non-carriers; OR = 1.45, p = 2.51 × 10-4 in single-copy carriers; OR = 2.38, p = 2.76 × 10-6 in two-copy carriers).
Conclusions: This study demonstrated that genetic variants at two novel susceptibility loci and the epistatic interaction between variants in LILR and TAP2 loci confer a risk of CD.
背景和目的:克罗恩病[CD]具有复杂的多基因遗传学,遗传率很高。目前,人们正努力通过在大量韩国人群中开展全基因组关联研究(GWAS)来确定与克罗恩病易感性相关的新型变异:方法:在一项荟萃分析中,利用来自 902 名韩国 CD 患者和 72 179 名对照者的全基因组变异数据,评估了与之前来自 1621 名 CD 患者和 4419 名对照者的韩国 GWAS 结果之间的遗传关联。使用带有交互作用项的多变量逻辑回归模型检验了感兴趣的 CD 风险变异之间的外显交互作用:结果:我们在ZBTB38附近和白细胞免疫球蛋白样受体[LILR]基因簇内发现了两个与CD风险相关的新遗传变异[p 结论:该研究证明了两个与CD风险相关的遗传变异:这项研究表明,两个新的易感基因位点上的遗传变异以及 LILR 和 TAP2 位点上的变异之间的表观相互作用会带来 CD 风险。
{"title":"Regulatory Variants on the Leukocyte Immunoglobulin-Like Receptor Gene Cluster are Associated with Crohn's Disease and Interact with Regulatory Variants for TAP2.","authors":"Kwangwoo Kim, Shin Ju Oh, Junho Lee, Ayeong Kwon, Chae-Yeon Yu, Sangsoo Kim, Chang Hwan Choi, Sang-Bum Kang, Tae Oh Kim, Dong Il Park, Chang Kyun Lee","doi":"10.1093/ecco-jcc/jjad127","DOIUrl":"10.1093/ecco-jcc/jjad127","url":null,"abstract":"<p><strong>Background and aims: </strong>Crohn's disease [CD] has a complex polygenic aetiology with high heritability. There is ongoing effort to identify novel variants associated with susceptibility to CD through a genome-wide association study [GWAS] in large Korean populations.</p><p><strong>Methods: </strong>Genome-wide variant data from 902 Korean patients with CD and 72 179 controls were used to assess the genetic associations in a meta-analysis with previous Korean GWAS results from 1621 patients with CD and 4419 controls. Epistatic interactions between CD-risk variants of interest were tested using a multivariate logistic regression model with an interaction term.</p><p><strong>Results: </strong>We identified two novel genetic associations with the risk of CD near ZBTB38 and within the leukocyte immunoglobulin-like receptor [LILR] gene cluster [p < 5 × 10-8], with highly consistent effect sizes between the two independent Korean cohorts. CD-risk variants in the LILR locus are known quantitative trait loci [QTL] for multiple LILR genes, of which LILRB2 directly interacts with various ligands including MHC class I molecules. The LILR lead variant exhibited a significant epistatic interaction with CD-associated regulatory variants for TAP2 involved in the antigen presentation of MHC class I molecules [p = 4.11 × 10-4], showing higher CD-risk effects of the TAP2 variant in individuals carrying more risk alleles of the LILR lead variant (odds ratio [OR] = 0.941, p = 0.686 in non-carriers; OR = 1.45, p = 2.51 × 10-4 in single-copy carriers; OR = 2.38, p = 2.76 × 10-6 in two-copy carriers).</p><p><strong>Conclusions: </strong>This study demonstrated that genetic variants at two novel susceptibility loci and the epistatic interaction between variants in LILR and TAP2 loci confer a risk of CD.</p>","PeriodicalId":15547,"journal":{"name":"Journal of Crohns & Colitis","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10256155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-27DOI: 10.1093/ecco-jcc/jjad108
Hannah Gordon, Johan Burisch, Pierre Ellul, Konstantinos Karmiris, Konstantinos Katsanos, Mariangela Allocca, Giorgos Bamias, Manuel Barreiro-de Acosta, Tasanee Braithwaite, Thomas Greuter, Catherine Harwood, Pascal Juillerat, Triana Lobaton, Ulf Müller-Ladner, Nurulamin Noor, Gianluca Pellino, Edoardo Savarino, Christoph Schramm, Alessandra Soriano, Jürgen Michael Stein, Mathieu Uzzan, Patrick F van Rheenen, Stephan R Vavricka, Maurizio Vecchi, Stephane Zuily, Torsten Kucharzik
{"title":"ECCO Guidelines on Extraintestinal Manifestations in Inflammatory Bowel Disease.","authors":"Hannah Gordon, Johan Burisch, Pierre Ellul, Konstantinos Karmiris, Konstantinos Katsanos, Mariangela Allocca, Giorgos Bamias, Manuel Barreiro-de Acosta, Tasanee Braithwaite, Thomas Greuter, Catherine Harwood, Pascal Juillerat, Triana Lobaton, Ulf Müller-Ladner, Nurulamin Noor, Gianluca Pellino, Edoardo Savarino, Christoph Schramm, Alessandra Soriano, Jürgen Michael Stein, Mathieu Uzzan, Patrick F van Rheenen, Stephan R Vavricka, Maurizio Vecchi, Stephane Zuily, Torsten Kucharzik","doi":"10.1093/ecco-jcc/jjad108","DOIUrl":"10.1093/ecco-jcc/jjad108","url":null,"abstract":"","PeriodicalId":15547,"journal":{"name":"Journal of Crohns & Colitis","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9668754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-27DOI: 10.1093/ecco-jcc/jjad118
Sebastiaan Ten Bokkel Huinink, Doranne Thomassen, Ewout W Steyerberg, Renske W M Pauwels, Maria J Casanova, Guillaume Bouguen, Joyce W Y Mak, Tamas Molnár, Alan J Lobo, Jacob B Seidelin, Aurelien Amiot, Geert D'Haens, Pauline Rivière, Luisa Guidi, Renata Bor, Wei-Chen Lin, Laurent Peyrin-Biroulet, Javier P Gisbert, C Janneke van der Woude, Annemarie C de Vries
Background: The risk of relapse after anti-tumour necrosis factor [TNF] therapy discontinuation in Crohn's disease patients with perianal fistulas [pCD] is unclear. We aimed to assess this risk.
Methods: A systematic literature search was conducted to identify cohort studies on the incidence of relapse following anti-TNF discontinuation in pCD patients. Individual participant data were requested from the original study cohorts. Inclusion criteria were age ≥16 years, pCD as a (co)indication for start of anti-TNF therapy, more than three doses, and remission of luminal and pCD at anti-TNF discontinuation. The primary outcome was the cumulative incidence of CD relapse using Kaplan-Meier estimates. Secondary outcomes included response to re-treatment and risk factors associated with relapse as assessed by Cox regression analysis.
Results: In total, 309 patients from 12 studies in ten countries were included. The median duration of anti-TNF treatment was 14 months [interquartile range 5.8-32.5]. Most patients were treated for pCD without active luminal disease [89%], received first-line anti-TNF therapy [87%], and continued immunomodulatory therapy following anti-TNF discontinuation [78%]. The overall cumulative incidence of relapse was 36% (95% confidence interval [CI] 25-48%) and 42% [95% CI 32-53%] at 1 and 2 years after anti-TNF discontinuation, respectively. Risk factors for relapse included smoking (hazard ratio [HR] 1.5 [1.0, 2.1]) and history of proctitis (HR 1.7 [1.1, 2.5]). The overall re-treatment response rate was 82%.
Conclusions: This individual participant data meta-analysis, on predominantly patients with pCD without active luminal disease and first-line anti-TNF therapy, shows that over half of patients remain in remission 2 years after anti-TNF discontinuation. Therefore, anti-TNF discontinuation may be considered in this subgroup.
{"title":"Discontinuation of Anti-Tumour Necrosis Factor Therapy in Patients with Perianal Fistulizing Crohn's Disease: Individual Participant Data Meta-Analysis of 309 Patients from 12 Studies.","authors":"Sebastiaan Ten Bokkel Huinink, Doranne Thomassen, Ewout W Steyerberg, Renske W M Pauwels, Maria J Casanova, Guillaume Bouguen, Joyce W Y Mak, Tamas Molnár, Alan J Lobo, Jacob B Seidelin, Aurelien Amiot, Geert D'Haens, Pauline Rivière, Luisa Guidi, Renata Bor, Wei-Chen Lin, Laurent Peyrin-Biroulet, Javier P Gisbert, C Janneke van der Woude, Annemarie C de Vries","doi":"10.1093/ecco-jcc/jjad118","DOIUrl":"10.1093/ecco-jcc/jjad118","url":null,"abstract":"<p><strong>Background: </strong>The risk of relapse after anti-tumour necrosis factor [TNF] therapy discontinuation in Crohn's disease patients with perianal fistulas [pCD] is unclear. We aimed to assess this risk.</p><p><strong>Methods: </strong>A systematic literature search was conducted to identify cohort studies on the incidence of relapse following anti-TNF discontinuation in pCD patients. Individual participant data were requested from the original study cohorts. Inclusion criteria were age ≥16 years, pCD as a (co)indication for start of anti-TNF therapy, more than three doses, and remission of luminal and pCD at anti-TNF discontinuation. The primary outcome was the cumulative incidence of CD relapse using Kaplan-Meier estimates. Secondary outcomes included response to re-treatment and risk factors associated with relapse as assessed by Cox regression analysis.</p><p><strong>Results: </strong>In total, 309 patients from 12 studies in ten countries were included. The median duration of anti-TNF treatment was 14 months [interquartile range 5.8-32.5]. Most patients were treated for pCD without active luminal disease [89%], received first-line anti-TNF therapy [87%], and continued immunomodulatory therapy following anti-TNF discontinuation [78%]. The overall cumulative incidence of relapse was 36% (95% confidence interval [CI] 25-48%) and 42% [95% CI 32-53%] at 1 and 2 years after anti-TNF discontinuation, respectively. Risk factors for relapse included smoking (hazard ratio [HR] 1.5 [1.0, 2.1]) and history of proctitis (HR 1.7 [1.1, 2.5]). The overall re-treatment response rate was 82%.</p><p><strong>Conclusions: </strong>This individual participant data meta-analysis, on predominantly patients with pCD without active luminal disease and first-line anti-TNF therapy, shows that over half of patients remain in remission 2 years after anti-TNF discontinuation. Therefore, anti-TNF discontinuation may be considered in this subgroup.</p>","PeriodicalId":15547,"journal":{"name":"Journal of Crohns & Colitis","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10821706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9774570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-30DOI: 10.1093/ecco-jcc/jjad113
Ryan C Ungaro, Harisha Kadali, Wenwen Zhang, Shashi Adsul, Walter Reinisch
Background and aims: The benefit of continuing 5-aminosalicylic acid [5-ASA] treatment when escalating to advanced therapies in patients with inflammatory bowel disease [IBD] is unclear. Vedolizumab is a gut-selective monoclonal anti-α4β7-integrin antibody used to treat moderate to severe IBD. Clinical trial data were analysed post hoc to assess the impact of 5-ASA co-treatment on vedolizumab efficacy and safety in patients with IBD.
Methods: Data were analysed from patients aged 18-80 years with moderate to severe ulcerative colitis [UC]/Crohn's disease [CD] receiving intravenous [IV]/subcutaneous [SC] vedolizumab. Efficacy data were from four studies [GEMINI 1 and 2 and VISIBLE 1 and 2]; safety data were from seven studies [GEMINI 1‒3 and long-term, VISIBLE 1, 2, and open-label extension]. The impact of 5-ASA co-treatment on clinical and endoscopic outcomes at Weeks 6 and 52 was assessed using multivariate analysis (adjusted odds ratios [aORs] with 95% confidence intervals [CIs]).
Results: There were no significant differences in UC clinical remission [Mayo score ≤2, no subscore >1] rates with vs without 5-ASA at Week 6 [20.7% vs 20.4%, respectively; aOR 0.77, 95% CI 0.43-1.38] or at Week 52 [45.1% vs 40.6%; aOR 1.14, 0.70-1.86], and in CD clinical remission [CD activity index score ≤150] rates at Week 6 [41.4% vs 35.1%; 1.26, 0.86-1.85] or at Week 52 [49.6% vs 37.8%; 1.35, 0.91-1.99]. The incidence of enteric and all infections in vedolizumab IV/SC-treated patients was low with and without 5-ASA.
Conclusion: Continuation of concomitant oral 5-ASA after starting vedolizumab had no significant impact on clinical and endoscopic outcomes.
{"title":"Impact of Concomitant 5-Aminosalicylic Acid Therapy on Vedolizumab Efficacy and Safety in Inflammatory Bowel Disease: Post Hoc Analyses of Clinical Trial Data.","authors":"Ryan C Ungaro, Harisha Kadali, Wenwen Zhang, Shashi Adsul, Walter Reinisch","doi":"10.1093/ecco-jcc/jjad113","DOIUrl":"10.1093/ecco-jcc/jjad113","url":null,"abstract":"<p><strong>Background and aims: </strong>The benefit of continuing 5-aminosalicylic acid [5-ASA] treatment when escalating to advanced therapies in patients with inflammatory bowel disease [IBD] is unclear. Vedolizumab is a gut-selective monoclonal anti-α4β7-integrin antibody used to treat moderate to severe IBD. Clinical trial data were analysed post hoc to assess the impact of 5-ASA co-treatment on vedolizumab efficacy and safety in patients with IBD.</p><p><strong>Methods: </strong>Data were analysed from patients aged 18-80 years with moderate to severe ulcerative colitis [UC]/Crohn's disease [CD] receiving intravenous [IV]/subcutaneous [SC] vedolizumab. Efficacy data were from four studies [GEMINI 1 and 2 and VISIBLE 1 and 2]; safety data were from seven studies [GEMINI 1‒3 and long-term, VISIBLE 1, 2, and open-label extension]. The impact of 5-ASA co-treatment on clinical and endoscopic outcomes at Weeks 6 and 52 was assessed using multivariate analysis (adjusted odds ratios [aORs] with 95% confidence intervals [CIs]).</p><p><strong>Results: </strong>There were no significant differences in UC clinical remission [Mayo score ≤2, no subscore >1] rates with vs without 5-ASA at Week 6 [20.7% vs 20.4%, respectively; aOR 0.77, 95% CI 0.43-1.38] or at Week 52 [45.1% vs 40.6%; aOR 1.14, 0.70-1.86], and in CD clinical remission [CD activity index score ≤150] rates at Week 6 [41.4% vs 35.1%; 1.26, 0.86-1.85] or at Week 52 [49.6% vs 37.8%; 1.35, 0.91-1.99]. The incidence of enteric and all infections in vedolizumab IV/SC-treated patients was low with and without 5-ASA.</p><p><strong>Conclusion: </strong>Continuation of concomitant oral 5-ASA after starting vedolizumab had no significant impact on clinical and endoscopic outcomes.</p><p><strong>Clinical trial identifiers: </strong>GEMINI 1: NCT00783718, EudraCT 2008-002782-32; GEMINI 2: NCT00783692, EudraCT 2008-00278-33; GEMINI 3: NCT01224171, EudraCT 2009-016488-12; GEMINI long-term safety study: NCT00790933, EudraCT 2008-002784-14; VISIBLE 1: NCT02611830, EudraCT 2015-000480-14; VISIBLE 2: NCT02611817, EudraCT 2015-000481-58; VISIBLE open-label extension: NCT02620046, EudraCT 2015-000482-31.</p>","PeriodicalId":15547,"journal":{"name":"Journal of Crohns & Colitis","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10798864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9873333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-30DOI: 10.1093/ecco-jcc/jjad117
Lorant Gonczi, Laszlo Lakatos, Petra A Golovics, Akos Ilias, Tunde Pandur, Gyula David, Zsuzsanna Erdelyi, Istvan Szita, Alex Al Khoury, Peter L Lakatos
Background and aims: Few population-based studies have investigated long-term surgery rates for Crohn's disease [CD]. Our aim was to analyse disease progression and surgery rates in a population-based cohort over different therapeutic eras, based on the time of diagnosis: cohort-A [1977-1995], cohort-B [1996-2008], and cohort-C [2009-2018].
Methods: A total of 946 incident CD patients were analysed (male/female: 496/450; median age at diagnosis: 28 years [y]; interquartile range [IQR]: 22-40]). Patient inclusion lasted between 1977 and 2018. Immunomodulators have become widespread in Hungary since the mid-1990s and biologic therapies since 2008. Patients were followed prospectively, with both in-hospital and outpatient records reviewed regularly.
Results: The probability of disease behaviour progression from inflammatory [B1] to stenosing or penetrating phenotype [B2/B3] significantly decreased (27.1 ± 5.3%/21.5 ± 2.5%/11.3 ± 2.2% in cohorts A/B/C, respectively, after 5 years; 44.3 ± 5.9%/30.6 ± 2.8%/16.1 ± 2.9% after 10 years, respectively; [pLogRank <0.001]). The probability of first resective surgery between cohorts A/B/C were 33.3 ± 3.8%/26.5 ± 2.1%/28.1 ± 2.4%, respectively, after 5 years; 46.1 ± 4.1%/32.6 ± 2.2%/33.0 ± 2.7% after 10 years, respectively; and 59.1 ± 4.0%/41.4 ± 2.6% [cohorts A/B] after 20 years. There was a significant decrease in first resective surgery risk between cohorts A and B [plog rank = 0.002]; however, no further decrease between cohorts B and C [plog rank = 0.665]. The cumulative probability of re-resection in cohorts A/B/C was decreasing over time (17.3 ± 4.1%/12.6 ± 2.6%/4.7 ± 2.0%, respectively, after 5 years [plog rank = 0.001]).
Conclusion: We report a continuous decline in reoperation rates and disease behaviour progression in CD over time, with the lowest values in the biologic era. In contrast, there was no further decrease in the probability of first major resective surgery after the immunosuppressive era.
{"title":"Declining Trends of Reoperations and Disease Behaviour Progression in Crohn's Disease over Different Therapeutic Eras-A Prospective, Population-Based Study from Western Hungary between 1977-2020, Data from the Veszprem Cohort.","authors":"Lorant Gonczi, Laszlo Lakatos, Petra A Golovics, Akos Ilias, Tunde Pandur, Gyula David, Zsuzsanna Erdelyi, Istvan Szita, Alex Al Khoury, Peter L Lakatos","doi":"10.1093/ecco-jcc/jjad117","DOIUrl":"10.1093/ecco-jcc/jjad117","url":null,"abstract":"<p><strong>Background and aims: </strong>Few population-based studies have investigated long-term surgery rates for Crohn's disease [CD]. Our aim was to analyse disease progression and surgery rates in a population-based cohort over different therapeutic eras, based on the time of diagnosis: cohort-A [1977-1995], cohort-B [1996-2008], and cohort-C [2009-2018].</p><p><strong>Methods: </strong>A total of 946 incident CD patients were analysed (male/female: 496/450; median age at diagnosis: 28 years [y]; interquartile range [IQR]: 22-40]). Patient inclusion lasted between 1977 and 2018. Immunomodulators have become widespread in Hungary since the mid-1990s and biologic therapies since 2008. Patients were followed prospectively, with both in-hospital and outpatient records reviewed regularly.</p><p><strong>Results: </strong>The probability of disease behaviour progression from inflammatory [B1] to stenosing or penetrating phenotype [B2/B3] significantly decreased (27.1 ± 5.3%/21.5 ± 2.5%/11.3 ± 2.2% in cohorts A/B/C, respectively, after 5 years; 44.3 ± 5.9%/30.6 ± 2.8%/16.1 ± 2.9% after 10 years, respectively; [pLogRank <0.001]). The probability of first resective surgery between cohorts A/B/C were 33.3 ± 3.8%/26.5 ± 2.1%/28.1 ± 2.4%, respectively, after 5 years; 46.1 ± 4.1%/32.6 ± 2.2%/33.0 ± 2.7% after 10 years, respectively; and 59.1 ± 4.0%/41.4 ± 2.6% [cohorts A/B] after 20 years. There was a significant decrease in first resective surgery risk between cohorts A and B [plog rank = 0.002]; however, no further decrease between cohorts B and C [plog rank = 0.665]. The cumulative probability of re-resection in cohorts A/B/C was decreasing over time (17.3 ± 4.1%/12.6 ± 2.6%/4.7 ± 2.0%, respectively, after 5 years [plog rank = 0.001]).</p><p><strong>Conclusion: </strong>We report a continuous decline in reoperation rates and disease behaviour progression in CD over time, with the lowest values in the biologic era. In contrast, there was no further decrease in the probability of first major resective surgery after the immunosuppressive era.</p>","PeriodicalId":15547,"journal":{"name":"Journal of Crohns & Colitis","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10798863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10120621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}