Pub Date : 2023-12-30DOI: 10.1093/ecco-jcc/jjad105
Maja Kopczynska, Benjamin Crooks, Liat Deutsch, Thomas Conley, Catherine Stansfield, Ashley Bond, Mattias Soop, Gordon Carlson, Simon Lal
Background and aims: Intestinal failure [IF] is a recognised complication of Crohn's disease [CD]. The aim of this study was to identify factors predicting the development and recurrence of CD in patients with IF [CD-IF], and their long-term outcomes.
Methods: This was a cohort study of adults with CD-IF admitted to a national UK IF reference centre between 2000 and 2021. Patients were followed from discharge with home parenteral nutrition [HPN] until death or February 28, 2021.
Results: In all, 124 patients were included; 47 [37.9%] changed disease location and 55 [44.4%] changed disease behaviour between CD and CD-IF diagnosis, with increased upper gastrointestinal involvement [4.0% vs 22.6% patients], p <0.001. Following IF diagnosis, 29/124 [23.4%] patients commenced CD prophylactic medical therapy; 18 [62.1%] had a history of stricturing or penetrating small bowel disease; and nine [31.0%] had ileocolonic phenotype brought back into continuity. The cumulative incidence of disease recurrence was 2.4% at 1 year, 16.3% at 5 years and 27.2% at 10 years; colon-in-continuity and prophylactic treatment were associated with an increased likelihood of disease recurrence. Catheter-related bloodstream infection [CRBSI] rate was 0.32 episodes/1000 catheter days, with no association between medical therapy and CRBSI rate.
Conclusions: This is the largest series reporting disease behaviour and long-term outcomes in CD-IF and the first describing prophylactic therapy use. The incidence of disease recurrence was low. Immunosuppressive therapy appears to be safe in HPN-dependent patients with no increased risk of CRBSI. The management of CD-IF needs to be tailored to the patient's surgical disease history alongside disease phenotype.
{"title":"Disease Recurrence and Long-term Outcomes Following the Development of Intestinal Failure in Crohn's Disease: Over 20 Years of Experience from a National Reference Centre.","authors":"Maja Kopczynska, Benjamin Crooks, Liat Deutsch, Thomas Conley, Catherine Stansfield, Ashley Bond, Mattias Soop, Gordon Carlson, Simon Lal","doi":"10.1093/ecco-jcc/jjad105","DOIUrl":"10.1093/ecco-jcc/jjad105","url":null,"abstract":"<p><strong>Background and aims: </strong>Intestinal failure [IF] is a recognised complication of Crohn's disease [CD]. The aim of this study was to identify factors predicting the development and recurrence of CD in patients with IF [CD-IF], and their long-term outcomes.</p><p><strong>Methods: </strong>This was a cohort study of adults with CD-IF admitted to a national UK IF reference centre between 2000 and 2021. Patients were followed from discharge with home parenteral nutrition [HPN] until death or February 28, 2021.</p><p><strong>Results: </strong>In all, 124 patients were included; 47 [37.9%] changed disease location and 55 [44.4%] changed disease behaviour between CD and CD-IF diagnosis, with increased upper gastrointestinal involvement [4.0% vs 22.6% patients], p <0.001. Following IF diagnosis, 29/124 [23.4%] patients commenced CD prophylactic medical therapy; 18 [62.1%] had a history of stricturing or penetrating small bowel disease; and nine [31.0%] had ileocolonic phenotype brought back into continuity. The cumulative incidence of disease recurrence was 2.4% at 1 year, 16.3% at 5 years and 27.2% at 10 years; colon-in-continuity and prophylactic treatment were associated with an increased likelihood of disease recurrence. Catheter-related bloodstream infection [CRBSI] rate was 0.32 episodes/1000 catheter days, with no association between medical therapy and CRBSI rate.</p><p><strong>Conclusions: </strong>This is the largest series reporting disease behaviour and long-term outcomes in CD-IF and the first describing prophylactic therapy use. The incidence of disease recurrence was low. Immunosuppressive therapy appears to be safe in HPN-dependent patients with no increased risk of CRBSI. The management of CD-IF needs to be tailored to the patient's surgical disease history alongside disease phenotype.</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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9671382","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 : 2023-12-30DOI: 10.1093/ecco-jcc/jjad114
Bjarki T Alexandersson, Anna Andreasson, Charlotte Hedin, Gabriella Broms, Peter T Schmidt, Anna Forsberg
Background and aims: Inflammatory bowel disease may cause long-standing inflammation and fibrosis and may increase the risk of adverse events in colonoscopy. We evaluated whether inflammatory bowel disease and other potential risk factors are associated with bleeding or perforation in a nationwide, population-based, Swedish study.
Methods: Data from 969 532 colonoscopies, including 164 012 [17%] on inflammatory bowel disease patients, between 2003 and 2019, were retrieved from the National Patient Registers. ICD-10 codes for bleeding [T810] and perforation [T812] within 30 days of the colonoscopy were recorded. Multivariable logistic regression was used to test if inflammatory bowel disease status, inpatient setting, time period, general anaesthesia, age, sex, endoscopic procedures, and antithrombotic treatment were associated with higher odds for bleeding and perforation.
Results: Bleeding and perforation were reported in 0.19% and 0.11% of all colonoscopies, respectively. Bleeding [odds ratio 0.66, p <0.001] and perforation [odds ratio 0.79, p <0.033] were less likely in colonoscopies in individuals with inflammatory bowel disease status. Bleeding and perforation were more common in inpatient than in outpatient inflammatory bowel disease colonoscopies. The odds for bleeding but not perforation increased between 2003 to 2019. General anaesthesia was associated with double the odds for perforation.
Conclusions: Individuals with inflammatory bowel disease did not have more adverse events compared with individuals without inflammatory bowel disease status. However, the inpatient setting was associated with more adverse events, particularly in inflammatory bowel disease status. General anaesthesia was associated with a greater risk of perforation.
{"title":"Inflammatory Bowel Disease Is not Linked to a Higher Rate of Adverse Events in Colonoscopy-a Nationwide Population-based Study in Sweden.","authors":"Bjarki T Alexandersson, Anna Andreasson, Charlotte Hedin, Gabriella Broms, Peter T Schmidt, Anna Forsberg","doi":"10.1093/ecco-jcc/jjad114","DOIUrl":"10.1093/ecco-jcc/jjad114","url":null,"abstract":"<p><strong>Background and aims: </strong>Inflammatory bowel disease may cause long-standing inflammation and fibrosis and may increase the risk of adverse events in colonoscopy. We evaluated whether inflammatory bowel disease and other potential risk factors are associated with bleeding or perforation in a nationwide, population-based, Swedish study.</p><p><strong>Methods: </strong>Data from 969 532 colonoscopies, including 164 012 [17%] on inflammatory bowel disease patients, between 2003 and 2019, were retrieved from the National Patient Registers. ICD-10 codes for bleeding [T810] and perforation [T812] within 30 days of the colonoscopy were recorded. Multivariable logistic regression was used to test if inflammatory bowel disease status, inpatient setting, time period, general anaesthesia, age, sex, endoscopic procedures, and antithrombotic treatment were associated with higher odds for bleeding and perforation.</p><p><strong>Results: </strong>Bleeding and perforation were reported in 0.19% and 0.11% of all colonoscopies, respectively. Bleeding [odds ratio 0.66, p <0.001] and perforation [odds ratio 0.79, p <0.033] were less likely in colonoscopies in individuals with inflammatory bowel disease status. Bleeding and perforation were more common in inpatient than in outpatient inflammatory bowel disease colonoscopies. The odds for bleeding but not perforation increased between 2003 to 2019. General anaesthesia was associated with double the odds for perforation.</p><p><strong>Conclusions: </strong>Individuals with inflammatory bowel disease did not have more adverse events compared with individuals without inflammatory bowel disease status. However, the inpatient setting was associated with more adverse events, particularly in inflammatory bowel disease status. General anaesthesia was associated with a greater risk of perforation.</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/PMC10798860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9752136","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/jjad109
Jayendra Seetharaman, Anshu Srivastava, Rajanikant R Yadav, Sumit K Singh, Prabhakar Mishra, Moinak Sen Sarma, Ujjal Poddar
Background and aims: Crohn's disease [CD] and intestinal tuberculosis [ITB] are often difficult to differentiate. Mesenteric fat hypertrophy is a feature of CD. We evaluated the utility of fat indices (visceral fat [VF] and subcutaneous fat [SF]) in differentiating CD and ITB in children.
Methods: Symptomatic children diagnosed to have CD or ITB based on recommended criteria were enrolled. Clinical, anthropometric, and laboratory details were noted. Abdominal fat was measured on computed tomography in supine position at the level of L4 vertebrae. VF and SF area was measured separately by a radiologist, blinded to the diagnosis. The sum of VF and SF was taken as total fat [TF]. VF/SF and VF/TF ratios were calculated.
Results: Thirty-four (age 14 years [10.8-17.0], 14 boys) children were recruited: 12 had CD [seven boys, age 13.0 years] and 22 had ITB [seven boys, age 14.5 years]. VF area was higher in CD compared to ITB (18.34 cm2 [15.62-40.01] vs 6.48 cm2 [2.65-21.96]; p = 0.012). The SF and TF area was similar in ITB and CD. The ratios of VF/SF (0.82 [0.57-1.5] vs 0.33 [0.16-0.48]; p = 0.004) and VF/TF (0.45 [0.36-0.60] vs 0.25 [0.13-0.32]; p = 0.004) were significantly higher in CD. On comparing CD and ITB in boys and girls separately, the difference was significant for boys but not for girls. A VF/SF ratio of 0.609 predicted CD with a good sensitivity [75%] and specificity [86.4%] [area under the curve 0.795, 95% confidence interval 0.636-0.955; p = 0.005].
Conclusion: The VF/SF ratio is a simple, non-invasive, objective parameter to differentiate CD and ITB in children, particularly boys. Larger studies are needed to validate this in girls.
背景和目的:克罗恩病 [CD] 和肠结核 [ITB] 通常很难区分。肠系膜脂肪肥厚是 CD 的一个特征。我们评估了脂肪指数(内脏脂肪[VF]和皮下脂肪[SF])在区分儿童克罗恩病和肠结核方面的效用:方法:根据推荐标准诊断为 CD 或 ITB 的无症状儿童入组。注意临床、人体测量和实验室细节。仰卧位时,在L4椎体水平通过计算机断层扫描测量腹部脂肪。VF和SF面积由一名放射科医生分别测量,该医生对诊断结果保密。VF和SF的总和为总脂肪[TF]。计算VF/SF和VF/TF比率:共招募了 34 名儿童(14 岁 [10.8-17.0],14 名男孩):其中 12 名儿童患有 CD(7 名男孩,13.0 岁),22 名儿童患有 ITB(7 名男孩,14.5 岁)。与 ITB 相比,CD 儿童的 VF 面积更大(18.34 平方厘米 [15.62-40.01] vs 6.48 平方厘米 [2.65-21.96];P = 0.012)。ITB 和 CD 的 SF 和 TF 面积相似。CD患儿的VF/SF(0.82 [0.57-1.5] vs 0.33 [0.16-0.48];p = 0.004)和VF/TF(0.45 [0.36-0.60] vs 0.25 [0.13-0.32];p = 0.004)之比明显高于ITB患儿。在分别比较男孩和女孩的 CD 和 ITB 时,男孩的差异显著,女孩则不显著。VF/SF比值为0.609可预测CD,具有良好的敏感性[75%]和特异性[86.4%][曲线下面积为0.795,95%置信区间为0.636-0.955;P = 0.005]:VF/SF比值是区分儿童(尤其是男孩)CD和ITB的一个简单、无创、客观的参数。需要进行更大规模的研究,以便在女孩中验证这一结果。
{"title":"Visceral Fat Indices: Do They Help Differentiate Crohn's Disease and Intestinal Tuberculosis in Children?","authors":"Jayendra Seetharaman, Anshu Srivastava, Rajanikant R Yadav, Sumit K Singh, Prabhakar Mishra, Moinak Sen Sarma, Ujjal Poddar","doi":"10.1093/ecco-jcc/jjad109","DOIUrl":"10.1093/ecco-jcc/jjad109","url":null,"abstract":"<p><strong>Background and aims: </strong>Crohn's disease [CD] and intestinal tuberculosis [ITB] are often difficult to differentiate. Mesenteric fat hypertrophy is a feature of CD. We evaluated the utility of fat indices (visceral fat [VF] and subcutaneous fat [SF]) in differentiating CD and ITB in children.</p><p><strong>Methods: </strong>Symptomatic children diagnosed to have CD or ITB based on recommended criteria were enrolled. Clinical, anthropometric, and laboratory details were noted. Abdominal fat was measured on computed tomography in supine position at the level of L4 vertebrae. VF and SF area was measured separately by a radiologist, blinded to the diagnosis. The sum of VF and SF was taken as total fat [TF]. VF/SF and VF/TF ratios were calculated.</p><p><strong>Results: </strong>Thirty-four (age 14 years [10.8-17.0], 14 boys) children were recruited: 12 had CD [seven boys, age 13.0 years] and 22 had ITB [seven boys, age 14.5 years]. VF area was higher in CD compared to ITB (18.34 cm2 [15.62-40.01] vs 6.48 cm2 [2.65-21.96]; p = 0.012). The SF and TF area was similar in ITB and CD. The ratios of VF/SF (0.82 [0.57-1.5] vs 0.33 [0.16-0.48]; p = 0.004) and VF/TF (0.45 [0.36-0.60] vs 0.25 [0.13-0.32]; p = 0.004) were significantly higher in CD. On comparing CD and ITB in boys and girls separately, the difference was significant for boys but not for girls. A VF/SF ratio of 0.609 predicted CD with a good sensitivity [75%] and specificity [86.4%] [area under the curve 0.795, 95% confidence interval 0.636-0.955; p = 0.005].</p><p><strong>Conclusion: </strong>The VF/SF ratio is a simple, non-invasive, objective parameter to differentiate CD and ITB in children, particularly boys. Larger studies are needed to validate this in girls.</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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10104133","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 : 2023-12-30DOI: 10.1093/ecco-jcc/jjad110
Tommaso L Parigi, Rosanna Cannatelli, Olga M Nardone, Irene Zammarchi, Uday Shivaji, Federica Furfaro, Davide Zardo, Paola Spaggiari, Rachele Del Sordo, Orsola Setti, Snehali Majumder, Samuel C L Smith, Silvio Danese, Alessandro Armuzzi, Vincenzo Villanacci, Subrata Ghosh, Marietta Iacucci
Backgrounds and aims: Absence of neutrophils is the minimum standard to consider histological remission of ulcerative colitis [UC]. The PICaSSO Histological Remission Index [PHRI] is a new simple index for UC, based only on the detection of neutrophils. We evaluate PHRI's correlation with endoscopy and its prognostic value compared with other established indices.
Methods: Consecutive patients with UC underwent colonoscopy at two referral centres [Birmingham, UK, and Milan, Italy,] and were followed up for 2 years. Correlation between histology (PHRI, Nancy [NHI], and Robarts [RHI] indexes) and endoscopy (Mayo Endoscopic Score [MES], Ulcerative Colitis Endoscopic Index of Severity [UCEIS], and PICaSSO index) was calculated as Spearman coefficients. Diagnostic performance of endoscopy was assessed with receiver operating characteristic [ROC] curves and outcome stratification with Kaplan-Meier curves.
Results: A total of 192 patients with UC was enrolled, representing all grades of endoscopic severity. Correlation between histology and endoscopy did not differ significantly when using PHRI instead of NHI or RHI. In particular, PHRI's correlation with MES, UCEIS, and PICaSSO was 0.745, 0.718, and 0.694, respectively. Endoscopically-assessed remission reflected the absence of neutrophils [PHRI = 0] with areas under the ROC curve of 0.905, 0.906, and 0.877 for MES, UCEIS, and PICaSSO, respectively. The hazard ratio for disease flare between patients in histological activity/remission was statistically similar [p >0.05] across indexes [2.752, 2.706, and 2.871 for RHI, NHI, and PHRI, respectively].
Conclusion: PHRI correlates with endoscopy and stratifies risk of relapse similarly to RHI and NHI. Neutrophil-only assessment of UC is a simple yet viable alternative to established histological scores.
{"title":"Neutrophil-only Histological Assessment of Ulcerative Colitis Correlates with Endoscopic Activity and Predicts Long-term Outcomes in a Multicentre Study.","authors":"Tommaso L Parigi, Rosanna Cannatelli, Olga M Nardone, Irene Zammarchi, Uday Shivaji, Federica Furfaro, Davide Zardo, Paola Spaggiari, Rachele Del Sordo, Orsola Setti, Snehali Majumder, Samuel C L Smith, Silvio Danese, Alessandro Armuzzi, Vincenzo Villanacci, Subrata Ghosh, Marietta Iacucci","doi":"10.1093/ecco-jcc/jjad110","DOIUrl":"10.1093/ecco-jcc/jjad110","url":null,"abstract":"<p><strong>Backgrounds and aims: </strong>Absence of neutrophils is the minimum standard to consider histological remission of ulcerative colitis [UC]. The PICaSSO Histological Remission Index [PHRI] is a new simple index for UC, based only on the detection of neutrophils. We evaluate PHRI's correlation with endoscopy and its prognostic value compared with other established indices.</p><p><strong>Methods: </strong>Consecutive patients with UC underwent colonoscopy at two referral centres [Birmingham, UK, and Milan, Italy,] and were followed up for 2 years. Correlation between histology (PHRI, Nancy [NHI], and Robarts [RHI] indexes) and endoscopy (Mayo Endoscopic Score [MES], Ulcerative Colitis Endoscopic Index of Severity [UCEIS], and PICaSSO index) was calculated as Spearman coefficients. Diagnostic performance of endoscopy was assessed with receiver operating characteristic [ROC] curves and outcome stratification with Kaplan-Meier curves.</p><p><strong>Results: </strong>A total of 192 patients with UC was enrolled, representing all grades of endoscopic severity. Correlation between histology and endoscopy did not differ significantly when using PHRI instead of NHI or RHI. In particular, PHRI's correlation with MES, UCEIS, and PICaSSO was 0.745, 0.718, and 0.694, respectively. Endoscopically-assessed remission reflected the absence of neutrophils [PHRI = 0] with areas under the ROC curve of 0.905, 0.906, and 0.877 for MES, UCEIS, and PICaSSO, respectively. The hazard ratio for disease flare between patients in histological activity/remission was statistically similar [p >0.05] across indexes [2.752, 2.706, and 2.871 for RHI, NHI, and PHRI, respectively].</p><p><strong>Conclusion: </strong>PHRI correlates with endoscopy and stratifies risk of relapse similarly to RHI and NHI. Neutrophil-only assessment of UC is a simple yet viable alternative to established histological scores.</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/PMC10798862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10104136","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/jjad106
Johan Burisch, Ekaterina Safroneeva, Raphael Laoun, Christopher Ma
Although ulcerative colitis [UC] shares many common pathways and therapeutic options with Crohn's disease [CD], CD patients are four times more likely to undergo surgery 10 years into their disease in the biological era and are more likely to have extraintestinal manifestations than UC patients. Early treatment in CD has been demonstrated to modify the natural history of the disease and potentially delay surgery. Previous reviews on this topic have borrowed their evidence from CD to make UC-specific recommendations. This review highlights the emergence of UC-specific data from larger cohort studies and a comprehensive individual patient data systemic review and meta-analysis to critically appraise evidence on the utility of early escalation to advanced therapies with respect to short-, medium-, and long-term outcomes. In UC, the utility of the early escalation concept for the purposes of changing the natural history, including reducing colectomy and hospitalizations, is not supported by the available data. Data on targeting clinical, biochemical, endoscopic, and histological outcomes are needed to demonstrate that they are meaningful with regard to achieving reductions in hospitalization and surgery, improving quality of life, and minimizing disability. Analyses of different populations of UC patients, such as those with 'relapsing & remitting' disease or with severe or complicated disease course, are urgently needed. The costs and risk/benefit profile of some of the newer advanced therapies should be carefully considered. In this clinical landscape, it appears premature to advocate an indiscriminate 'one size fits all' approach to escalating to advanced therapies early during the course of UC.
{"title":"Lack of Benefit for Early Escalation to Advanced Therapies in Ulcerative Colitis: Critical Appraisal of Current Evidence.","authors":"Johan Burisch, Ekaterina Safroneeva, Raphael Laoun, Christopher Ma","doi":"10.1093/ecco-jcc/jjad106","DOIUrl":"10.1093/ecco-jcc/jjad106","url":null,"abstract":"<p><p>Although ulcerative colitis [UC] shares many common pathways and therapeutic options with Crohn's disease [CD], CD patients are four times more likely to undergo surgery 10 years into their disease in the biological era and are more likely to have extraintestinal manifestations than UC patients. Early treatment in CD has been demonstrated to modify the natural history of the disease and potentially delay surgery. Previous reviews on this topic have borrowed their evidence from CD to make UC-specific recommendations. This review highlights the emergence of UC-specific data from larger cohort studies and a comprehensive individual patient data systemic review and meta-analysis to critically appraise evidence on the utility of early escalation to advanced therapies with respect to short-, medium-, and long-term outcomes. In UC, the utility of the early escalation concept for the purposes of changing the natural history, including reducing colectomy and hospitalizations, is not supported by the available data. Data on targeting clinical, biochemical, endoscopic, and histological outcomes are needed to demonstrate that they are meaningful with regard to achieving reductions in hospitalization and surgery, improving quality of life, and minimizing disability. Analyses of different populations of UC patients, such as those with 'relapsing & remitting' disease or with severe or complicated disease course, are urgently needed. The costs and risk/benefit profile of some of the newer advanced therapies should be carefully considered. In this clinical landscape, it appears premature to advocate an indiscriminate 'one size fits all' approach to escalating to advanced therapies early during the course of UC.</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/PMC10798867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10047478","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/jjad112
Bruce E Sands, Stefan Schreiber, Irina Blumenstein, Michael V Chiorean, Ryan C Ungaro, David T Rubin
The emergence of advanced therapies [eg, biologics, Janus kinase inhibitors] over the past few decades has revolutionised the treatment of ulcerative colitis. However, the limitations of these therapies leave an unmet need for safer and more effective or convenient treatment options. There is growing interest in the development of novel oral small molecule therapies for the treatment of ulcerative colitis. Ozanimod is an oral small molecule therapy that is approved in the USA, the European Union, and other countries as the first sphingosine 1-phosphate receptor modulator for the treatment of moderately to severely active ulcerative colitis in adults. This review provides guidance for ozanimod use for the treatment of ulcerative colitis, based on the prescribing information, clinical trial and real-world data, and the authors' clinical experiences. This guidance outlines patient characteristics to consider when deciding if ozanimod treatment is suitable and describes how to educate patients on risks and best practices. It also details the nature and frequency of monitoring during treatment, which should be adapted to the individual patient based on pre-existing risk factors and events that possibly occur during treatment. This review also provides insights into the patient characteristics and clinical scenarios best suited for ozanimod treatment, based on its efficacy, safety profile, and risks compared with other therapies.
{"title":"Clinician's Guide to Using Ozanimod for the Treatment of Ulcerative Colitis.","authors":"Bruce E Sands, Stefan Schreiber, Irina Blumenstein, Michael V Chiorean, Ryan C Ungaro, David T Rubin","doi":"10.1093/ecco-jcc/jjad112","DOIUrl":"10.1093/ecco-jcc/jjad112","url":null,"abstract":"<p><p>The emergence of advanced therapies [eg, biologics, Janus kinase inhibitors] over the past few decades has revolutionised the treatment of ulcerative colitis. However, the limitations of these therapies leave an unmet need for safer and more effective or convenient treatment options. There is growing interest in the development of novel oral small molecule therapies for the treatment of ulcerative colitis. Ozanimod is an oral small molecule therapy that is approved in the USA, the European Union, and other countries as the first sphingosine 1-phosphate receptor modulator for the treatment of moderately to severely active ulcerative colitis in adults. This review provides guidance for ozanimod use for the treatment of ulcerative colitis, based on the prescribing information, clinical trial and real-world data, and the authors' clinical experiences. This guidance outlines patient characteristics to consider when deciding if ozanimod treatment is suitable and describes how to educate patients on risks and best practices. It also details the nature and frequency of monitoring during treatment, which should be adapted to the individual patient based on pre-existing risk factors and events that possibly occur during treatment. This review also provides insights into the patient characteristics and clinical scenarios best suited for ozanimod treatment, based on its efficacy, safety profile, and risks compared with other therapies.</p>","PeriodicalId":15547,"journal":{"name":"Journal of Crohns & Colitis","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10798866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9770161","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/jjad119
Moira Paroni, Gabriella Leccese, Valeria Ranzani, Giorgia Moschetti, Matteo Chiara, Federica Perillo, Sara Ferri, Francesca Clemente, Daniele Noviello, Francesco Simone Conforti, Stefano Ferrero, Bhavna Karnani, Roberto Bosotti, Chiara Vasco, Serena Curti, Maria Cristina Crosti, Paola Gruarin, Grazisa Rossetti, Maria Pia Conte, Maurizio Vecchi, Massimiliano Pagani, Paolo Landini, Federica Facciotti, Sergio Abrignani, Flavio Caprioli, Jens Geginat
IFNγ-producing ex-Th17 cells ['Th1/17'] were shown to play a key pathogenic role in experimental colitis and are abundant in the intestine. Here, we identified and characterised a novel, potentially colitogenic subset of Th17 cells in the intestine of patients with Crohn's disease [CD]. Human Th17 cells expressing CCR5 ['pTh17'] co-expressed T-bet and RORC/γt and produced very high levels of IL-17, together with IFN-γ. They had a gene signature of Th17 effector cells and were distinct from established Th1/17 cells. pTh17 cells, but not Th1/17 cells, were associated with intestinal inflammation in CD, and decreased upon successful anti-TNF therapy with infliximab. Conventional CCR5[-]Th17 cells differentiated to pTh17 cells with IL-23 in vitro. Moreover, anti-IL-23 therapy with risankizumab strongly reduced pTh17 cells in the intestine. Importantly, intestinal pTh17 cells were selectively activated by adherent-invasive Escherichia coli [AIEC], but not by a commensal/probiotic E. coli strain. AIEC induced high levels of IL-23 and RANTES from dendritic cells [DC]. Intestinal CCR5+Th1/17 cells responded instead to cytomegalovirus and were reduced in ulcerative colitis [UC], suggesting an unexpected protective role. In conclusion, we identified an IL-23-inducible subset of human intestinal Th17 cells. pTh17 cells produced high levels of pro-inflammatory cytokines, were selectively associated with intestinal inflammation in CD, and responded to CD-associated AIEC, suggesting a key colitogenic role.
{"title":"An Intestinal Th17 Subset is Associated with Inflammation in Crohn's Disease and Activated by Adherent-invasive Escherichia coli.","authors":"Moira Paroni, Gabriella Leccese, Valeria Ranzani, Giorgia Moschetti, Matteo Chiara, Federica Perillo, Sara Ferri, Francesca Clemente, Daniele Noviello, Francesco Simone Conforti, Stefano Ferrero, Bhavna Karnani, Roberto Bosotti, Chiara Vasco, Serena Curti, Maria Cristina Crosti, Paola Gruarin, Grazisa Rossetti, Maria Pia Conte, Maurizio Vecchi, Massimiliano Pagani, Paolo Landini, Federica Facciotti, Sergio Abrignani, Flavio Caprioli, Jens Geginat","doi":"10.1093/ecco-jcc/jjad119","DOIUrl":"10.1093/ecco-jcc/jjad119","url":null,"abstract":"<p><p>IFNγ-producing ex-Th17 cells ['Th1/17'] were shown to play a key pathogenic role in experimental colitis and are abundant in the intestine. Here, we identified and characterised a novel, potentially colitogenic subset of Th17 cells in the intestine of patients with Crohn's disease [CD]. Human Th17 cells expressing CCR5 ['pTh17'] co-expressed T-bet and RORC/γt and produced very high levels of IL-17, together with IFN-γ. They had a gene signature of Th17 effector cells and were distinct from established Th1/17 cells. pTh17 cells, but not Th1/17 cells, were associated with intestinal inflammation in CD, and decreased upon successful anti-TNF therapy with infliximab. Conventional CCR5[-]Th17 cells differentiated to pTh17 cells with IL-23 in vitro. Moreover, anti-IL-23 therapy with risankizumab strongly reduced pTh17 cells in the intestine. Importantly, intestinal pTh17 cells were selectively activated by adherent-invasive Escherichia coli [AIEC], but not by a commensal/probiotic E. coli strain. AIEC induced high levels of IL-23 and RANTES from dendritic cells [DC]. Intestinal CCR5+Th1/17 cells responded instead to cytomegalovirus and were reduced in ulcerative colitis [UC], suggesting an unexpected protective role. In conclusion, we identified an IL-23-inducible subset of human intestinal Th17 cells. pTh17 cells produced high levels of pro-inflammatory cytokines, were selectively associated with intestinal inflammation in CD, and responded to CD-associated AIEC, suggesting a key colitogenic role.</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/PMC10798865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9882625","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}
Background and aims: Many patients have endoscopic evidence of recurrent Crohn's disease [CD] at 1 year after intestinal resection. These lesions predict future clinical recurrence. We endoscopically evaluated postoperative anastomotic lesions in CD patients from a large cohort of postoperative CD patients.
Methods: We retrospectively enrolled CD patients who underwent surgical resection between 2008 and 2013 at 19 inflammatory bowel disease [IBD]-specialist institutions. The initial analyses included patients who underwent ileocolonoscopy ~1 year after intestinal resection. Follow-up analyses assessed any changes in the endoscopic findings over time. We evaluated the postoperative endoscopic findings, which were classified into four categories [no lesion, mild, intermediate, severe] at the sites of the anastomotic line and peri-anastomosis.
Results: In total, 267 CD patients underwent postoperative ileocolonoscopy. Postoperative anastomotic lesions were widely detected in index ileocolonoscopy [61.0%] and were more frequently detected in follow-up ileocolonoscopy [74.9%]. Endoscopic severity also increased. Patients with intermediate or severe peri-anastomotic or anastomotic line lesions at the index ileocolonoscopy required significantly more interventions, including endoscopic dilatation or surgery, than patients with mild lesions or no lesions.
Conclusions: Frequent anastomotic lesions were observed at the postoperative index ileocolonoscopy. These gradually increased for subsequent ileocolonoscopy, even in the biologic era. Regarding lesions on the anastomotic line, intermediate lesions on the anastomotic line [e.g. irregular or deep ulcers] might be considered recurrent disease, and mild lesions [e.g. linear superficial ulcers] might be considered non-recurrent disease. Prospective studies are needed to resolve this issue, including treatment enhancement.
背景和目的:许多患者在肠道切除术后 1 年,内镜检查发现克罗恩病 [CD] 复发。这些病变可预测未来的临床复发。我们对一大批术后 CD 患者的术后吻合口病变进行了内镜评估:我们回顾性地纳入了 2008 年至 2013 年期间在 19 家炎症性肠病 [IBD] 专家机构接受手术切除的 CD 患者。初步分析包括肠切除术后约 1 年接受回肠结肠镜检查的患者。随访分析评估了内镜检查结果随时间推移发生的任何变化。我们评估了术后内镜检查结果,并将吻合口线和吻合口周围部位的内镜检查结果分为四类[无病变、轻度、中度、重度]:共有267名CD患者接受了术后回肠结肠镜检查。术后吻合口病变在索引回肠结肠镜检查中被广泛发现[61.0%],在随访回肠结肠镜检查中被更频繁地发现[74.9%]。内镜检查的严重程度也有所增加。与病变轻微或无病变的患者相比,在索引回肠结肠镜检查中发现中度或重度吻合口周围病变或吻合口线病变的患者需要更多的干预措施,包括内镜扩张或手术:结论:术后首次回肠结肠镜检查发现吻合口经常出现病变。这些病变在随后的回肠结肠镜检查中逐渐增加,即使在生物时代也是如此。关于吻合口线上的病变,吻合口线上的中度病变(如不规则或深度溃疡)可视为复发性疾病,而轻度病变(如线状浅表溃疡)可视为非复发性疾病。要解决这个问题,需要进行前瞻性研究,包括加强治疗。
{"title":"Endoscopic Lesions of Postoperative Anastomotic Area in Patients With Crohn's Disease in the Biologic Era: A Japanese Multi-Centre Nationwide Cohort Study.","authors":"Takeshi Ueda, Fumikazu Koyama, Akira Sugita, Hiroki Ikeuchi, Kitaro Futami, Kouhei Fukushima, Riichiro Nezu, Hideki Iijima, Tsunekazu Mizushima, Michio Itabashi, Kazuhiro Watanabe, Keisuke Hata, Takahide Shinagawa, Katsuyoshi Matsuoka, Kento Takenaka, Makoto Sasaki, Manabu Nagayama, Hironori Yamamoto, Masaru Shinozaki, Mikihiro Fujiya, Jun Kato, Yoshitaka Ueno, Shinji Tanaka, Yoshiki Okita, Yoshinari Hashimoto, Taku Kobayashi, Kazutaka Koganei, Motoi Uchino, Hisao Fujii, Yasuo Suzuki, Tadakazu Hisamatsu","doi":"10.1093/ecco-jcc/jjad116","DOIUrl":"10.1093/ecco-jcc/jjad116","url":null,"abstract":"<p><strong>Background and aims: </strong>Many patients have endoscopic evidence of recurrent Crohn's disease [CD] at 1 year after intestinal resection. These lesions predict future clinical recurrence. We endoscopically evaluated postoperative anastomotic lesions in CD patients from a large cohort of postoperative CD patients.</p><p><strong>Methods: </strong>We retrospectively enrolled CD patients who underwent surgical resection between 2008 and 2013 at 19 inflammatory bowel disease [IBD]-specialist institutions. The initial analyses included patients who underwent ileocolonoscopy ~1 year after intestinal resection. Follow-up analyses assessed any changes in the endoscopic findings over time. We evaluated the postoperative endoscopic findings, which were classified into four categories [no lesion, mild, intermediate, severe] at the sites of the anastomotic line and peri-anastomosis.</p><p><strong>Results: </strong>In total, 267 CD patients underwent postoperative ileocolonoscopy. Postoperative anastomotic lesions were widely detected in index ileocolonoscopy [61.0%] and were more frequently detected in follow-up ileocolonoscopy [74.9%]. Endoscopic severity also increased. Patients with intermediate or severe peri-anastomotic or anastomotic line lesions at the index ileocolonoscopy required significantly more interventions, including endoscopic dilatation or surgery, than patients with mild lesions or no lesions.</p><p><strong>Conclusions: </strong>Frequent anastomotic lesions were observed at the postoperative index ileocolonoscopy. These gradually increased for subsequent ileocolonoscopy, even in the biologic era. Regarding lesions on the anastomotic line, intermediate lesions on the anastomotic line [e.g. irregular or deep ulcers] might be considered recurrent disease, and mild lesions [e.g. linear superficial ulcers] might be considered non-recurrent disease. Prospective studies are needed to resolve this issue, including treatment enhancement.</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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9833874","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 : 2023-12-30DOI: 10.1093/ecco-jcc/jjad115
Robert Gilmore, Wei Lian Tan, Richard Fernandes, Yoon-Kyo An, Jakob Begun
Background and aims: Acute severe ulcerative colitis [ASUC] is a medical emergency treated with intravenous steroids followed by infliximab or cyclosporin in the case of steroid failure with emergent colectomy required in refractory or severe cases. Case series have reported on the effectiveness of tofacitinib for refractory disease, but data regarding the effectiveness of upadacitinib in this setting have not been previously reported. We describe the use of upadacitinib therapy for steroid-refractory ASUC in patients with prior loss of response to infliximab.
Methods: Six patients who received upadacitinib for steroid-refractory ASUC were identified at two Australian tertiary inflammatory bowel disease centres. Patients were followed for up to 16 weeks after discharge with clinical, biochemical and intestinal ultrasound [IUS] outcomes.
Results: All six patients demonstrated clinical response to upadacitinib induction during their inpatient admission. Four patients achieved corticosteroid-free clinical remission by week 8, including complete resolution of rectal bleeding and transmural healing assessed by IUS, and sustained clinical remission at week 16. One patient proceeded to colectomy at week 15 due to refractory disease. No adverse events directly attributable to upadacitinib were identified.
Conclusions: Upadacitinib may have a role as a safe and effective salvage therapy for steroid-refractory ASUC in patients who have previously failed to respond to infliximab therapy. Prospective studies are required to determine the safety and efficacy of upadacitinib use in this setting before routine use can be recommended.
{"title":"Upadacitinib Salvage Therapy for Infliximab-Experienced Patients with Acute Severe Ulcerative Colitis.","authors":"Robert Gilmore, Wei Lian Tan, Richard Fernandes, Yoon-Kyo An, Jakob Begun","doi":"10.1093/ecco-jcc/jjad115","DOIUrl":"10.1093/ecco-jcc/jjad115","url":null,"abstract":"<p><strong>Background and aims: </strong>Acute severe ulcerative colitis [ASUC] is a medical emergency treated with intravenous steroids followed by infliximab or cyclosporin in the case of steroid failure with emergent colectomy required in refractory or severe cases. Case series have reported on the effectiveness of tofacitinib for refractory disease, but data regarding the effectiveness of upadacitinib in this setting have not been previously reported. We describe the use of upadacitinib therapy for steroid-refractory ASUC in patients with prior loss of response to infliximab.</p><p><strong>Methods: </strong>Six patients who received upadacitinib for steroid-refractory ASUC were identified at two Australian tertiary inflammatory bowel disease centres. Patients were followed for up to 16 weeks after discharge with clinical, biochemical and intestinal ultrasound [IUS] outcomes.</p><p><strong>Results: </strong>All six patients demonstrated clinical response to upadacitinib induction during their inpatient admission. Four patients achieved corticosteroid-free clinical remission by week 8, including complete resolution of rectal bleeding and transmural healing assessed by IUS, and sustained clinical remission at week 16. One patient proceeded to colectomy at week 15 due to refractory disease. No adverse events directly attributable to upadacitinib were identified.</p><p><strong>Conclusions: </strong>Upadacitinib may have a role as a safe and effective salvage therapy for steroid-refractory ASUC in patients who have previously failed to respond to infliximab therapy. Prospective studies are required to determine the safety and efficacy of upadacitinib use in this setting before routine use can be recommended.</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/PMC10798861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10120620","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/jjad107
Natalie Yu, Danujan Sriranganathan, Gareth J Walker, Aleksejs Sazonovs, Helen Wilding, Christopher Roberts, Nicholas A Kennedy, Tariq Ahmad, Ray K Boyapati, Nik S Ding, Jonathan P Segal
Background and aims: Nudix hydrolase 15 [NUDT15] genetic variants confer an increased risk of thiopurine-induced leukopenia [TIL]; however, their global prevalence in inflammatory bowel disease [IBD] patients is unknown. We aimed to evaluate the global prevalence of NUDT15 variants in IBD patients and incidence of TIL in these patients.
Methods: Six databases were searched from inception until July 2022. Studies reporting the frequency of any NUDT15 variant and/or frequency of leukopenia in adult IBD patients with these variants were included. A random effects model was performed to estimate the pooled prevalence of variants, incidence of early [≤8 weeks] and late [>8 weeks] leukopenia, and relative risk of developing leukopenia.
Results: Twenty studies comprising 5232 patients were included. The pooled prevalence of the *1/*3 c.415C > T C/T diplotype was 13% (95% confidence interval [CI]: 10-18%), *3/*3 c.415C > T T/T diplotype was 2% [95% CI: 1-2%], *1/*5 c.52G > A G/A diplotype was 2% [95% CI: 1-3%], and *1/*6 c.36_37insGGAGTC ins/- diplotype was 7% [95% CI: 4-12%]. The pooled prevalence of *1/*3 was high in Japanese [20%, 95% CI: 16-24%] and Chinese patients [18%, 95% CI: 12-27%]. The incidence of early leukopenia was 20% [95% CI: 16-26%] in *1/*3 patients, 99% [95% CI: 7-100%] in *3/*3 patients, and 49% [95% CI: 29-69%] in *1/*6 patients. The incidence of late leukopenia was 36% [95% CI: 26-49%] in *1/*3 patients.
Conclusions: NUDT15 variants are common and strongly predict TIL in IBD patients. Pre-treatment NUDT15 genotyping should be considered particularly in Asian populations, to guide thiopurine dosing and prevent myelotoxicity.
{"title":"Prevalence of NUDT15 Genetic Variants and Incidence of Thiopurine-induced Leukopenia in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.","authors":"Natalie Yu, Danujan Sriranganathan, Gareth J Walker, Aleksejs Sazonovs, Helen Wilding, Christopher Roberts, Nicholas A Kennedy, Tariq Ahmad, Ray K Boyapati, Nik S Ding, Jonathan P Segal","doi":"10.1093/ecco-jcc/jjad107","DOIUrl":"10.1093/ecco-jcc/jjad107","url":null,"abstract":"<p><strong>Background and aims: </strong>Nudix hydrolase 15 [NUDT15] genetic variants confer an increased risk of thiopurine-induced leukopenia [TIL]; however, their global prevalence in inflammatory bowel disease [IBD] patients is unknown. We aimed to evaluate the global prevalence of NUDT15 variants in IBD patients and incidence of TIL in these patients.</p><p><strong>Methods: </strong>Six databases were searched from inception until July 2022. Studies reporting the frequency of any NUDT15 variant and/or frequency of leukopenia in adult IBD patients with these variants were included. A random effects model was performed to estimate the pooled prevalence of variants, incidence of early [≤8 weeks] and late [>8 weeks] leukopenia, and relative risk of developing leukopenia.</p><p><strong>Results: </strong>Twenty studies comprising 5232 patients were included. The pooled prevalence of the *1/*3 c.415C > T C/T diplotype was 13% (95% confidence interval [CI]: 10-18%), *3/*3 c.415C > T T/T diplotype was 2% [95% CI: 1-2%], *1/*5 c.52G > A G/A diplotype was 2% [95% CI: 1-3%], and *1/*6 c.36_37insGGAGTC ins/- diplotype was 7% [95% CI: 4-12%]. The pooled prevalence of *1/*3 was high in Japanese [20%, 95% CI: 16-24%] and Chinese patients [18%, 95% CI: 12-27%]. The incidence of early leukopenia was 20% [95% CI: 16-26%] in *1/*3 patients, 99% [95% CI: 7-100%] in *3/*3 patients, and 49% [95% CI: 29-69%] in *1/*6 patients. The incidence of late leukopenia was 36% [95% CI: 26-49%] in *1/*3 patients.</p><p><strong>Conclusions: </strong>NUDT15 variants are common and strongly predict TIL in IBD patients. Pre-treatment NUDT15 genotyping should be considered particularly in Asian populations, to guide thiopurine dosing and prevent myelotoxicity.</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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10029835","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}