Introduction: Collagenous colitis (CC) is a disabling disease primarily affecting elderly women. Sparse, well-documented treatment modalities exist, except for budesonide. Long term and repetitive treatment with budesonide is often necessary. Rifaximin is a poorly absorbed antibiotic with a positive modulatory effect on gut microbiota. In this randomised, double-blind, placebo-controlled single center trial, we test the effect of adding rifaximin in continuation to budesonide on relapse rates in collagenous colitis. Methods: Eligible patients with active, biopsy verified CC received oral budesonide during a 6-week open-label induction phase. Patients in clinical remission after four weeks of treatment were randomised to receive either rifaximin or placebo for four weeks. Results: Fifteen patients were randomised to receive either rifaximin (n=7) or placebo (n=8). At 12-week follow-up, two patients in the rifaximin group were still in remission and none in the placebo group (p = 0.2). The median number of days in remission in the rifaximin group was 42 (IQR 33-126) compared to 18.5 (IQR 10.5-51.5) in the placebo group (P = 0.189). At 12-week follow-up the relapse rate per 100 person-days in the placebo group was higher (3.25 (1.40-6.41)) than in the rifaximin group (1.33 (0.43-3.10)). Conclusion: Although not statistically significant (p = 0.0996), the study suggests a potential improvement in relapse rates within the rifaximin group compared to the placebo group. A major limitation in the study is the small sample size.
{"title":"Rifaximin-treatment for collagenous colitis: A randomised, double-blind, placebo-controlled trial","authors":"Sabine Becker, Louise B. Grode, O. Bonderup","doi":"10.1159/000536124","DOIUrl":"https://doi.org/10.1159/000536124","url":null,"abstract":"Introduction: Collagenous colitis (CC) is a disabling disease primarily affecting elderly women. Sparse, well-documented treatment modalities exist, except for budesonide. Long term and repetitive treatment with budesonide is often necessary. Rifaximin is a poorly absorbed antibiotic with a positive modulatory effect on gut microbiota. In this randomised, double-blind, placebo-controlled single center trial, we test the effect of adding rifaximin in continuation to budesonide on relapse rates in collagenous colitis.\u0000Methods: Eligible patients with active, biopsy verified CC received oral budesonide during a 6-week open-label induction phase. Patients in clinical remission after four weeks of treatment were randomised to receive either rifaximin or placebo for four weeks. \u0000Results: Fifteen patients were randomised to receive either rifaximin (n=7) or placebo (n=8). At 12-week follow-up, two patients in the rifaximin group were still in remission and none in the placebo group (p = 0.2). The median number of days in remission in the rifaximin group was 42 (IQR 33-126) compared to 18.5 (IQR 10.5-51.5) in the placebo group (P = 0.189). At 12-week follow-up the relapse rate per 100 person-days in the placebo group was higher (3.25 (1.40-6.41)) than in the rifaximin group (1.33 (0.43-3.10)).\u0000Conclusion: Although not statistically significant (p = 0.0996), the study suggests a potential improvement in relapse rates within the rifaximin group compared to the placebo group. A major limitation in the study is the small sample size.","PeriodicalId":13605,"journal":{"name":"Inflammatory Intestinal Diseases","volume":"56 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139602041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
F. Pelizzaro, R. Cardin, Giulia Sarasini, M. Minotto, Chiara Carlotto, Matteo Fassan, Michela Palo, Fabio Farinati, Fabiana Zingone
MicroRNAs (miRNAs) are small, non-coding RNA molecules involved in regulating gene expression. Many studies, mostly conducted on pediatric patients, suggested that oxidative stress and several miRNAs may play an important role in coeliac disease (CeD) pathogenesis. However, the interplay between oxidative stress and miRNA regulatory functions in CeD remains to be clarified. In this review, we aimed to perform a literature review on the role of miRNAs and oxidative stress in adult CeD patients and to analyze their potential interactions. In this direction, we also reported the preliminary results of a pilot study we recently performed.
{"title":"Crosstalk between microRNAs and Oxidative stress in coeliac disease.","authors":"F. Pelizzaro, R. Cardin, Giulia Sarasini, M. Minotto, Chiara Carlotto, Matteo Fassan, Michela Palo, Fabio Farinati, Fabiana Zingone","doi":"10.1159/000536107","DOIUrl":"https://doi.org/10.1159/000536107","url":null,"abstract":"MicroRNAs (miRNAs) are small, non-coding RNA molecules involved in regulating gene expression. Many studies, mostly conducted on pediatric patients, suggested that oxidative stress and several miRNAs may play an important role in coeliac disease (CeD) pathogenesis. However, the interplay between oxidative stress and miRNA regulatory functions in CeD remains to be clarified. In this review, we aimed to perform a literature review on the role of miRNAs and oxidative stress in adult CeD patients and to analyze their potential interactions. In this direction, we also reported the preliminary results of a pilot study we recently performed.\u0000\u0000","PeriodicalId":13605,"journal":{"name":"Inflammatory Intestinal Diseases","volume":"96 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139601979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rintaro Moroi, Y. Kakuta, Hiroshi Nagai, Yusuke Shimoyama, Takeo Naito, H. Shiga, Y. Kinouchi, Atsushi Masamune
Introduction: Limited data exist regarding the prevalence and clinical practice involving generic drugs and biosimilars for treating ulcerative colitis (UC) in Japan. We aimed to clarify the clinical usage of these generic drugs and biosimilars for UC treatment in Japan using a nationwide database. Methods: We collected data from 30,675 UC cases, along with their prescriptions for both generic drugs or biosimilars and their original counterparts, using a medical claims database provided by DeSC Healthcare, Inc. We calculated the prescription and penetration rates of generic drugs and biosimilars and demonstrated the transition of these rates. Additionally, the cumulative retention rates between infliximab originator and biosimilar were compared using the Kaplan–Meier method. Results: The prescription rate of generic mesalazine increased from approximately 10% in 2015 to over 30% in 2021. Although the prescription rate of generic molecular targeting drugs (MTDs) also increased from approximately 0.15% in 2014 to 2.5% in 2021, the increment was lower than that of generic mesalazine. The penetration rates of generic 5-aminosalicylic acid and tacrolimus ranged from over 30% to approximately 50%. Infliximab biosimilar achieved an approximate 20% penetration rate, whereas adalimumab achieved< 5%. The cumulative retention rates did not differ between infliximab originator and biosimilar. Conclusions: The penetration rates of generics and biosimilars for UC treatment are relatively low compared with those for treatment in other fields and the goal of Ministry of Health, Labor, and Welfare. Several countermeasures are necessary for the widespread use of generics and biosimilars, ultimately contributing to cost-effective and sustainable healthcare delivery.
{"title":"Clinical utilization of generic drugs and biosimilars for ulcerative colitis treatment: Insights from a nationwide database study in Japan","authors":"Rintaro Moroi, Y. Kakuta, Hiroshi Nagai, Yusuke Shimoyama, Takeo Naito, H. Shiga, Y. Kinouchi, Atsushi Masamune","doi":"10.1159/000536146","DOIUrl":"https://doi.org/10.1159/000536146","url":null,"abstract":"Introduction: Limited data exist regarding the prevalence and clinical practice involving generic drugs and biosimilars for treating ulcerative colitis (UC) in Japan. We aimed to clarify the clinical usage of these generic drugs and biosimilars for UC treatment in Japan using a nationwide database.\u0000Methods: We collected data from 30,675 UC cases, along with their prescriptions for both generic drugs or biosimilars and their original counterparts, using a medical claims database provided by DeSC Healthcare, Inc. We calculated the prescription and penetration rates of generic drugs and biosimilars and demonstrated the transition of these rates. Additionally, the cumulative retention rates between infliximab originator and biosimilar were compared using the Kaplan–Meier method.\u0000Results: The prescription rate of generic mesalazine increased from approximately 10% in 2015 to over 30% in 2021. Although the prescription rate of generic molecular targeting drugs (MTDs) also increased from approximately 0.15% in 2014 to 2.5% in 2021, the increment was lower than that of generic mesalazine. The penetration rates of generic 5-aminosalicylic acid and tacrolimus ranged from over 30% to approximately 50%. Infliximab biosimilar achieved an approximate 20% penetration rate, whereas adalimumab achieved< 5%. The cumulative retention rates did not differ between infliximab originator and biosimilar.\u0000Conclusions: The penetration rates of generics and biosimilars for UC treatment are relatively low compared with those for treatment in other fields and the goal of Ministry of Health, Labor, and Welfare. Several countermeasures are necessary for the widespread use of generics and biosimilars, ultimately contributing to cost-effective and sustainable healthcare delivery. \u0000","PeriodicalId":13605,"journal":{"name":"Inflammatory Intestinal Diseases","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139445108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. Kiyohara, H. Yamazaki, Kei Moriya, Naohiko Akimoto, S. Kawai, Kento Takenaka, Tomohiro Fukuda, Keiichi Tominaga, Junji Umeno, S. Shinzaki, Yusuke Honzawa, Tomohisa Takagi, Hitoshi Ichikawa, Toshiyuki Endo, R. Ozaki, Akira Andoh, K. Matsuoka, Toshifumi Hibi, Taku Kobayashi
Introduction Whether white blood cell (WBC) counts are predictors for the effectiveness of thiopurine treatment in ulcerative colitis (UC) has been inconclusive in previous studies with small sample sizes. We investigated the association between WBC counts and future relapses in UC patients in a large-scale multi-center study. Methods This retrospective cohort study enrolled a total of 723 UC patients in remission from 33 hospitals and followed up for three years. Relapse was defined as a need for treatment intensification. The risk of relapse was compared among patients with the baseline WBC counts<3000/µL (N=31), 3000–4000/µL (N=167), 4000–5000/µL (N=241), and ≥5000/µL (N=284) using a Cox regression model analysis. Moreover, exploratory analyses were conducted to identify other factors predicting relapse. Results During a median follow-up period of 1095 (interquartile range, 1032–1119) days, relapse occurred in 17.2% (125/723). In a crude analysis, WBC counts were not associated with relapse; hazard ratios (HRs) [95% confidence interval (CI)] were 1.50 [0.74–3.06], 1.02 [0.66–1.59] and 0.67 [0.43–1.05] in WBC<3000/µL, 3000–4000/µL, and 4000–5000/µL groups, respectively (WBC≥5000/µL group, as reference). Multivariable-adjusted analyses showed similar results; HRs [95% CI] were 1.21 [0.59–2.49], 1.08 [0.69–1.69], and 0.69 [0.44–1.07], in <3000/µL, 3000–4000/µL, and 4000–5000/µL group, respectively. In the exploratory analyses, thiopurine use <1 year and a mean corpuscular volume <90 fL were predictors for relapse. Discussion/Conclusion WBC counts were not predictors for future relapses in patients with UC treated with thiopurine as a maintenance therapy.
{"title":"White blood cell counts and future relapse in ulcerative colitis under low-dose thiopurine treatment in real-world practice: a three year Japanese multi-center retrospective cohort study.","authors":"H. Kiyohara, H. Yamazaki, Kei Moriya, Naohiko Akimoto, S. Kawai, Kento Takenaka, Tomohiro Fukuda, Keiichi Tominaga, Junji Umeno, S. Shinzaki, Yusuke Honzawa, Tomohisa Takagi, Hitoshi Ichikawa, Toshiyuki Endo, R. Ozaki, Akira Andoh, K. Matsuoka, Toshifumi Hibi, Taku Kobayashi","doi":"10.1159/000535889","DOIUrl":"https://doi.org/10.1159/000535889","url":null,"abstract":"Introduction Whether white blood cell (WBC) counts are predictors for the effectiveness of thiopurine treatment in ulcerative colitis (UC) has been inconclusive in previous studies with small sample sizes. We investigated the association between WBC counts and future relapses in UC patients in a large-scale multi-center study. Methods This retrospective cohort study enrolled a total of 723 UC patients in remission from 33 hospitals and followed up for three years. Relapse was defined as a need for treatment intensification. The risk of relapse was compared among patients with the baseline WBC counts<3000/µL (N=31), 3000–4000/µL (N=167), 4000–5000/µL (N=241), and ≥5000/µL (N=284) using a Cox regression model analysis. Moreover, exploratory analyses were conducted to identify other factors predicting relapse. Results During a median follow-up period of 1095 (interquartile range, 1032–1119) days, relapse occurred in 17.2% (125/723). In a crude analysis, WBC counts were not associated with relapse; hazard ratios (HRs) [95% confidence interval (CI)] were 1.50 [0.74–3.06], 1.02 [0.66–1.59] and 0.67 [0.43–1.05] in WBC<3000/µL, 3000–4000/µL, and 4000–5000/µL groups, respectively (WBC≥5000/µL group, as reference). Multivariable-adjusted analyses showed similar results; HRs [95% CI] were 1.21 [0.59–2.49], 1.08 [0.69–1.69], and 0.69 [0.44–1.07], in <3000/µL, 3000–4000/µL, and 4000–5000/µL group, respectively. In the exploratory analyses, thiopurine use <1 year and a mean corpuscular volume <90 fL were predictors for relapse. Discussion/Conclusion WBC counts were not predictors for future relapses in patients with UC treated with thiopurine as a maintenance therapy.","PeriodicalId":13605,"journal":{"name":"Inflammatory Intestinal Diseases","volume":"27 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139150052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Limited data exist on the efficacy of combination therapy with ustekinumab and budesonide in patients with Crohn’s disease. Our objective was to compare the clinical outcomes of ustekinumab and budesonide combination therapy with those of ustekinumab monotherapy. Methods: In this Phase 2 single-center, double-blind, randomized controlled trial, we assigned 19 patients with Crohn’s disease with a Crohn’s disease activity index (CDAI) equal to or greater than 220 and less than 450 in a 1:1 ratio to receive ustekinumab and budesonide or ustekinumab for 32 weeks. The primary endpoint was the clinical remission rate at 8 weeks. The secondary endpoints were the clinical remission rate at 32 weeks and mucosal healing rates at 8 and 32 weeks. Results: Of 19 patients, the mean age was 37.8 years, and 42.1% were women (CDAI ≥220 and <450). There was no difference between combination therapy and ustekinumab monotherapy in terms of clinical remission rates (50.0% vs. 30.0%, P=0.39 at 8 weeks and 37.5% vs. 20.0%, P=0.41) and mucosal healing rates (75.0% vs. 90.0%, P= 0.40 and 37.5% vs. 60.0%, P=0.34 at 8 and 32 weeks, respectively). The most common adverse event was an exacerbation of Crohn’s. There were no differences in safety profiles between the two groups. Conclusions: Our study showed no difference between ustekinumab monotherapy and ustekinumab and budesonide combination therapy in terms of the induction and maintenance of remission (trial registration number: jRCTs021200013).
关于ustekinumab和布地奈德联合治疗克罗恩病患者的疗效的数据有限。我们的目的是比较ustekinumab和布地奈德联合治疗与ustekinumab单药治疗的临床结果。方法:在这项2期单中心、双盲、随机对照试验中，我们将19例克罗恩病活动性指数(CDAI)等于或大于220且小于450的克罗恩病患者按1:1的比例分配给ustekinumab和布地奈德或ustekinumab治疗32周。主要终点是8周时的临床缓解率。次要终点是32周的临床缓解率和8周和32周的粘膜愈合率。结果:19例患者平均年龄37.8岁，女性占42.1% (CDAI≥220，<450)。联合治疗和ustekinumab单药治疗在临床缓解率(50.0% vs. 30.0%， 8周时P=0.39; 37.5% vs. 20.0%， P=0.41)和粘膜愈合率(75.0% vs. 90.0%， P= 0.40; 37.5% vs. 60.0%， 8周和32周时P=0.34)方面没有差异。最常见的不良事件是克罗恩病的恶化。两组之间在安全性方面没有差异。结论:我们的研究显示，在诱导和维持缓解方面，ustekinumab单药治疗与ustekinumab和布地奈德联合治疗没有差异(试验注册号:jRCTs021200013)。
{"title":"The Efficacy of Combination Therapy with Ustekinumab and Budesonide for Crohn's Disease: A Randomized Controlled Trial","authors":"Rintaro Moroi, Kasumi Hishinuma, Yumi Sugawara, Kotaro Nochioka, Yusuke Shimoyama, Takeo Naito, Hisashi Shiga, Yoichi Kakuta, Yoshitaka Kinouchi, Ichiro Tsuji, Atsushi Masamune","doi":"10.1159/000535070","DOIUrl":"https://doi.org/10.1159/000535070","url":null,"abstract":"Introduction: Limited data exist on the efficacy of combination therapy with ustekinumab and budesonide in patients with Crohn’s disease. Our objective was to compare the clinical outcomes of ustekinumab and budesonide combination therapy with those of ustekinumab monotherapy. Methods: In this Phase 2 single-center, double-blind, randomized controlled trial, we assigned 19 patients with Crohn’s disease with a Crohn’s disease activity index (CDAI) equal to or greater than 220 and less than 450 in a 1:1 ratio to receive ustekinumab and budesonide or ustekinumab for 32 weeks. The primary endpoint was the clinical remission rate at 8 weeks. The secondary endpoints were the clinical remission rate at 32 weeks and mucosal healing rates at 8 and 32 weeks. Results: Of 19 patients, the mean age was 37.8 years, and 42.1% were women (CDAI ≥220 and <450). There was no difference between combination therapy and ustekinumab monotherapy in terms of clinical remission rates (50.0% vs. 30.0%, P=0.39 at 8 weeks and 37.5% vs. 20.0%, P=0.41) and mucosal healing rates (75.0% vs. 90.0%, P= 0.40 and 37.5% vs. 60.0%, P=0.34 at 8 and 32 weeks, respectively). The most common adverse event was an exacerbation of Crohn’s. There were no differences in safety profiles between the two groups. Conclusions: Our study showed no difference between ustekinumab monotherapy and ustekinumab and budesonide combination therapy in terms of the induction and maintenance of remission (trial registration number: jRCTs021200013).","PeriodicalId":13605,"journal":{"name":"Inflammatory Intestinal Diseases","volume":"76 23","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135092977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lovisa Röjler, Amiko M. Uchida, John J. Garber, Olof Stephansson, Jonas Söderling, Bjorn Roelstraete, Jonas F. Ludvigsson
Introduction: Eosinophilic esophagitis (EoE) is a chronic, allergic inflammatory disease of the esophagus. It has a peak incidence in the 2nd and 3rd decades of life. Despite this, little is known about pregnancy outcomes in patients with EoE. Methods: Using a validated histopathologic and nationwide population-based cohort for the diagnosis of EoE, we examined maternal and fetal outcomes, with preterm birth as the primary outcome, in females with EoE compared to matched controls. Odds ratios (ORs) were calculated using logistic regression. Results: Between 1992 and 2016, we identified 19 females with EoE who gave birth to 23 children (reference births: n = 115). There was 1 (4.3%) preterm birth in the EoE cohort versus 8 (7.0%) in the reference cohort (OR = 0.60; 95% CI = 0.07–5.14). Secondary fetal outcomes included stillbirth, neonatal death, small for gestational age, low birth weight (LBW), and low Apgar score. Of these, LBW (<2,500 g) in patients with EoE compared to controls correlated to an OR of 12.42 (95% CI = 1.26–122.42); however, this finding was based on very low numbers. The remaining fetal outcomes were not significantly different between females with EoE and controls. Secondary pregnancy and maternal outcomes including induction of labor, instrumental delivery, gestational diabetes, or pre-eclampsia were not significantly different between patients with EoE and controls. Discussion/Conclusion: Overall in this nationwide cohort study, we did not find increased association of preterm birth in patients with EoE.
{"title":"Pregnancy outcomes in females with eosinophilic esophagitis – a nationwide population-based study","authors":"Lovisa Röjler, Amiko M. Uchida, John J. Garber, Olof Stephansson, Jonas Söderling, Bjorn Roelstraete, Jonas F. Ludvigsson","doi":"10.1159/000534412","DOIUrl":"https://doi.org/10.1159/000534412","url":null,"abstract":"<b><i>Introduction:</i></b> Eosinophilic esophagitis (EoE) is a chronic, allergic inflammatory disease of the esophagus. It has a peak incidence in the 2nd and 3rd decades of life. Despite this, little is known about pregnancy outcomes in patients with EoE. <b><i>Methods:</i></b> Using a validated histopathologic and nationwide population-based cohort for the diagnosis of EoE, we examined maternal and fetal outcomes, with preterm birth as the primary outcome, in females with EoE compared to matched controls. Odds ratios (ORs) were calculated using logistic regression. <b><i>Results:</i></b> Between 1992 and 2016, we identified 19 females with EoE who gave birth to 23 children (reference births: <i>n</i> = 115). There was 1 (4.3%) preterm birth in the EoE cohort versus 8 (7.0%) in the reference cohort (OR = 0.60; 95% CI = 0.07–5.14). Secondary fetal outcomes included stillbirth, neonatal death, small for gestational age, low birth weight (LBW), and low Apgar score. Of these, LBW (&lt;2,500 g) in patients with EoE compared to controls correlated to an OR of 12.42 (95% CI = 1.26–122.42); however, this finding was based on very low numbers. The remaining fetal outcomes were not significantly different between females with EoE and controls. Secondary pregnancy and maternal outcomes including induction of labor, instrumental delivery, gestational diabetes, or pre-eclampsia were not significantly different between patients with EoE and controls. <b><i>Discussion/Conclusion:</i></b> Overall in this nationwide cohort study, we did not find increased association of preterm birth in patients with EoE.","PeriodicalId":13605,"journal":{"name":"Inflammatory Intestinal Diseases","volume":"468 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135546527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Leucine-rich alpha-2-glycoprotein (LRG) is a potential biomarker for disease activity and reflects mucosal healing in patients with ulcerative colitis (UC). However, only a few studies have described a detailed sensitivity analysis of LRG in predicting mucosal healing in patients. This study aimed to evaluate the association between LRG and the endoscopic activity of UC and its predictability for mucosal healing and explore the utility and clinical application of LRG. Methods: The diagnostic accuracy of biomarkers, including LRG, in predicting the endoscopic activity of UC was evaluated. All consecutive patients who underwent total colonoscopy between April 2021 and September 2022 were included. The Mayo endoscopic subscore (MES) was used for assessing endoscopic activity. Furthermore, endoscopic remission was defined as an MES of ≤1. Clinical activity was evaluated based on stool frequency and bloody stool. Receiver operating characteristic curve analysis and binary logistic regression were performed to assess the diagnostic accuracy of the biomarkers. We evaluated LRG trends and treatment response in patients with MES≥2 who underwent induction therapy. Results: This study comprised 214 patients. The proportions of endoscopically- and clinically active patients were 33.6% and 49.1%, respectively. LRG had an area under the curve (AUC) of 0.856, with a higher diagnostic accuracy than other biomarkers, such as C-reactive protein, leukocyte, neutrophil, platelet, and albumin. The cutoff value for LRG was 15.6 μg/mL (sensitivity, 72.2%; specificity, 86.6%). Using the MES, patients with higher scores had higher LRG levels than those with lower scores. The cutoff value, AUC, sensitivity, and specificity varied with a higher AUC for left-sided colitis and pancolitis than for proctitis. Logistic regression analysis showed that LRG was an independent predictor of endoscopic remission using multivariate analysis, even with the factor of clinical activity. The change ratio of LRG pre- and post-treatment was statistically significant in the higher LRG group. Discussion/Conclusion: LRG reflected endoscopic activity independently, regardless of clinical symptoms. An LRG below the cutoff value could indicate a significantly low probability of endoscopic activity in asymptomatic patients, and follow-up endoscopy (not for cancer screening) may be unnecessary. Furthermore, a higher LRG level might be more useful as an indicator of treatment efficacy.
{"title":"Novel utility of leucine-rich alpha 2-glycoprotein as a biomarker in ulcerative colitis: a predictor of endoscopic remission independent of symptoms","authors":"Tomoyuki Hayashi, Kazuya Kitamura, Masaaki Usami, Masaki Miyazawa, Masaki Nishitani, Akihiro Dejima, Makoto Yamamoto, Shotaro Kawase, Masaya Funaki, Noriaki Orita, Hidetoshi Nakagawa, Koki Morita, Noriho Iida, Akihiro Seki, Kouki Nio, Hidenori Kido, Hideo Takayama, Yuta Takeuchi, Shinya Yamada, Hajime Takatori, Mari Shimada, Hiroto Saito, Daisuke Yamamoto, Tadashi Toyama, Taro Yamashita","doi":"10.1159/000534001","DOIUrl":"https://doi.org/10.1159/000534001","url":null,"abstract":"Introduction: Leucine-rich alpha-2-glycoprotein (LRG) is a potential biomarker for disease activity and reflects mucosal healing in patients with ulcerative colitis (UC). However, only a few studies have described a detailed sensitivity analysis of LRG in predicting mucosal healing in patients. This study aimed to evaluate the association between LRG and the endoscopic activity of UC and its predictability for mucosal healing and explore the utility and clinical application of LRG. Methods: The diagnostic accuracy of biomarkers, including LRG, in predicting the endoscopic activity of UC was evaluated. All consecutive patients who underwent total colonoscopy between April 2021 and September 2022 were included. The Mayo endoscopic subscore (MES) was used for assessing endoscopic activity. Furthermore, endoscopic remission was defined as an MES of ≤1. Clinical activity was evaluated based on stool frequency and bloody stool. Receiver operating characteristic curve analysis and binary logistic regression were performed to assess the diagnostic accuracy of the biomarkers. We evaluated LRG trends and treatment response in patients with MES≥2 who underwent induction therapy. Results: This study comprised 214 patients. The proportions of endoscopically- and clinically active patients were 33.6% and 49.1%, respectively. LRG had an area under the curve (AUC) of 0.856, with a higher diagnostic accuracy than other biomarkers, such as C-reactive protein, leukocyte, neutrophil, platelet, and albumin. The cutoff value for LRG was 15.6 μg/mL (sensitivity, 72.2%; specificity, 86.6%). Using the MES, patients with higher scores had higher LRG levels than those with lower scores. The cutoff value, AUC, sensitivity, and specificity varied with a higher AUC for left-sided colitis and pancolitis than for proctitis. Logistic regression analysis showed that LRG was an independent predictor of endoscopic remission using multivariate analysis, even with the factor of clinical activity. The change ratio of LRG pre- and post-treatment was statistically significant in the higher LRG group. Discussion/Conclusion: LRG reflected endoscopic activity independently, regardless of clinical symptoms. An LRG below the cutoff value could indicate a significantly low probability of endoscopic activity in asymptomatic patients, and follow-up endoscopy (not for cancer screening) may be unnecessary. Furthermore, a higher LRG level might be more useful as an indicator of treatment efficacy.","PeriodicalId":13605,"journal":{"name":"Inflammatory Intestinal Diseases","volume":"20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135546528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Ustekinumab is an IgG1 kappa monoclonal antibody directed against the common p40 subunit of interleukin-12 and interleukin-23, which activate Th1- and Th17-mediated immune responses, respectively. It has proven efficacy for the treatment of moderate to severe ulcerative colitis (UC) in the UNIFI Phase III clinical trial; however, data on its efficacy in the real world is limited. In this study, we aimed to assess the real-world efficacy of ustekinumab. Methods: This observational study included 30 patients with UC who received ustekinumab from April 2020 to April 2022. We examined demographic information, disease type and activity (Mayo score, partial Mayo score [PMS]), use of biologics, concomitant use of predonisolone (PSL), 8-week ustekinumab clinical response rate, remission induction rate, 44- and 152-week remission maintenance rate, continuation rate, and 44-week steroid-free remission rate. The primary outcomes were the short- and long-term efficacy of ustekinumab. Results: Included patients (53% women; mean age: 41.2 years [16–80 years]) had an average disease duration of 86 weeks. Mayo’s score (median) was 7.4 and the PMS was 5.4. Two (7%), 24 (80%), and four (13%) patients had a Mayo endoscopic sub-score (MES) of MES1, MES2, and MES3, respectively. The median serum CRP was 1.0 mg/dL. Five patients had no history of biotherapy (naive), while 8 and 17 had a history of one and two or more biologic agents, respectively. Eight patients were PSL-resistant and 22 were PSL-dependent. The 8-week clinical response rate was 73%, and the clinical remission induction rate was 70%. The remission maintenance rates at 44 and 152 weeks were 67% and 63%, respectively. The ustekinumab retention rate was 67% (86-week mean follow-up period). Regarding biologic failure cases, the clinical response rate in the failure group with up to one biologic agent (including naive cases) was 84.6%, which was higher than the 58.0% rate in the failure group with two or more biologic agents (p=0.06). Steroid-free remission rates at 44 and 152 weeks were 63% each. In the logistic regression analysis parameters for discontinuation of ustekinumab, only PMS remained significant after multivariate analysis (p=0.018). Conclusion: Our study showed short-term and long-term ustekinumab effectiveness, especially with comparative low disease activity.
{"title":"Real-World Data on Short-Term and Long-Term Treatment Results of Ustekinumab in Patients with Steroid-Resistant/Dependent Ulcerative Colitis","authors":"Yoriaki Komeda, George Tribonias, Masashi Kono, Kohei Handa, Shunsuke Omoto, Mamoru Takenaka, Satoru Hagiwara, Naoko Tsuji, Naoshi Nishida, Hiroshi Kashida, Masatoshi Kudo","doi":"10.1159/000534457","DOIUrl":"https://doi.org/10.1159/000534457","url":null,"abstract":"Introduction: Ustekinumab is an IgG1 kappa monoclonal antibody directed against the common p40 subunit of interleukin-12 and interleukin-23, which activate Th1- and Th17-mediated immune responses, respectively. It has proven efficacy for the treatment of moderate to severe ulcerative colitis (UC) in the UNIFI Phase III clinical trial; however, data on its efficacy in the real world is limited. In this study, we aimed to assess the real-world efficacy of ustekinumab. Methods: This observational study included 30 patients with UC who received ustekinumab from April 2020 to April 2022. We examined demographic information, disease type and activity (Mayo score, partial Mayo score [PMS]), use of biologics, concomitant use of predonisolone (PSL), 8-week ustekinumab clinical response rate, remission induction rate, 44- and 152-week remission maintenance rate, continuation rate, and 44-week steroid-free remission rate. The primary outcomes were the short- and long-term efficacy of ustekinumab. Results: Included patients (53% women; mean age: 41.2 years [16–80 years]) had an average disease duration of 86 weeks. Mayo’s score (median) was 7.4 and the PMS was 5.4. Two (7%), 24 (80%), and four (13%) patients had a Mayo endoscopic sub-score (MES) of MES1, MES2, and MES3, respectively. The median serum CRP was 1.0 mg/dL. Five patients had no history of biotherapy (naive), while 8 and 17 had a history of one and two or more biologic agents, respectively. Eight patients were PSL-resistant and 22 were PSL-dependent. The 8-week clinical response rate was 73%, and the clinical remission induction rate was 70%. The remission maintenance rates at 44 and 152 weeks were 67% and 63%, respectively. The ustekinumab retention rate was 67% (86-week mean follow-up period). Regarding biologic failure cases, the clinical response rate in the failure group with up to one biologic agent (including naive cases) was 84.6%, which was higher than the 58.0% rate in the failure group with two or more biologic agents (p=0.06). Steroid-free remission rates at 44 and 152 weeks were 63% each. In the logistic regression analysis parameters for discontinuation of ustekinumab, only PMS remained significant after multivariate analysis (p=0.018). Conclusion: Our study showed short-term and long-term ustekinumab effectiveness, especially with comparative low disease activity.","PeriodicalId":13605,"journal":{"name":"Inflammatory Intestinal Diseases","volume":"468 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135546531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matthew D. Coates, Shannon Dalessio, August Stuart, Vonn Walter, Andrew Tinsley, Kofi Clarke, Emmanuelle D. Williams
Introduction: Hypoalgesic, or “silent”, inflammatory bowel disease (IBD) is a poorly understood condition that has been associated with poor clinical outcomes. There is evidence that lifestyle factors, including diet, exercise and substance use can influence inflammatory activity and symptoms in IBD. It is unclear, though, whether these issues impact pain experience in IBD. We performed this study to evaluate the potential relationship between several key lifestyle factors and silent IBD. Methods: We performed a retrospective analysis using an IBD natural history registry based in a single tertiary care referral center. We compared demographic and clinical features in two patient cohorts defined using data from simultaneous pain surveys and ileocolonoscopy: a) active IBD without pain (silent IBD), and b) active IBD with pain. We also evaluated the relative incidence of characteristics related to diet, exercise, sexual activity and substance abuse. Results: One hundred eighty IBD patients had active disease and 69 (38.3%) exhibited silent IBD. Silent IBD patients exhibited incidences of disease type, location, and severity as pain-perceiving IBD patients. Silent IBD patients were more likely to be male and less likely to exhibit anxiety and/or depression or to use cannabis, analgesic medication or corticosteroids. There were no significant differences in dietary, exercise-related or sexual activities between silent and pain-perceiving IBD patients. Conclusions: Silent IBD was associated with reduced incidence of substance and analgesic medication use. No relationships were found between silent IBD and diet, exercise or sexual activity, though specific elements of each require further dedicated study.
{"title":"Lifestyle Factors and Silent Inflammatory Bowel Disease","authors":"Matthew D. Coates, Shannon Dalessio, August Stuart, Vonn Walter, Andrew Tinsley, Kofi Clarke, Emmanuelle D. Williams","doi":"10.1159/000534413","DOIUrl":"https://doi.org/10.1159/000534413","url":null,"abstract":"Introduction: Hypoalgesic, or “silent”, inflammatory bowel disease (IBD) is a poorly understood condition that has been associated with poor clinical outcomes. There is evidence that lifestyle factors, including diet, exercise and substance use can influence inflammatory activity and symptoms in IBD. It is unclear, though, whether these issues impact pain experience in IBD. We performed this study to evaluate the potential relationship between several key lifestyle factors and silent IBD. Methods: We performed a retrospective analysis using an IBD natural history registry based in a single tertiary care referral center. We compared demographic and clinical features in two patient cohorts defined using data from simultaneous pain surveys and ileocolonoscopy: a) active IBD without pain (silent IBD), and b) active IBD with pain. We also evaluated the relative incidence of characteristics related to diet, exercise, sexual activity and substance abuse. Results: One hundred eighty IBD patients had active disease and 69 (38.3%) exhibited silent IBD. Silent IBD patients exhibited incidences of disease type, location, and severity as pain-perceiving IBD patients. Silent IBD patients were more likely to be male and less likely to exhibit anxiety and/or depression or to use cannabis, analgesic medication or corticosteroids. There were no significant differences in dietary, exercise-related or sexual activities between silent and pain-perceiving IBD patients. Conclusions: Silent IBD was associated with reduced incidence of substance and analgesic medication use. No relationships were found between silent IBD and diet, exercise or sexual activity, though specific elements of each require further dedicated study.","PeriodicalId":13605,"journal":{"name":"Inflammatory Intestinal Diseases","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135789880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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