Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.0516
A Buisson, A Amiot, M Nachury, R Altwegg, M Serrero, T Guilmoteau, X Treton, L Caillo, L Vuitton, G Bouguen, B Pereira, M Fumery
Background STRIDE 2 recommendations define clinical remission as no rectal bleeding and normalization of stool frequency in patients with ulcerative colitis (UC), without including bowel urgency (BU) despite its negative impact on quality of life. In this large multicenter cohort, we aimed to assess whether the persistence of BU after induction therapy is independently associated with poor long-term outcomes in patients with UC. Methods From a multicenter retrospective study, we included consecutive UC adult patients previously exposed to at least one anti-TNF agent, with partial Mayo score (pMS) > 2, who started biologics or small molecules between Jan2019 and June2022. BU was defined as a binary criterion based on the SCCAI definition. The primary endpoint was the time to drug discontinuation due to active UC. Secondary endpoints were time to relapse, time to colectomy as well as steroid-free clinical remission (pMS ≤ 2) (CFREM), endoscopic remission (CFREM + Mayo endoscopic score (MES) ≤ 1), and mucosal healing (CFREM + MES ≤ 1 + histological remission i.e. Nancy index ≤ 1) at last follow-up. Results Among 473 patients with UC, 270 were assessed for BU after induction therapy (week 16) (mean age 43.0±17.0 years-old, median UC duration 6 [3-11] years, female gender=54.0%, pancolitis=45.9%). The median follow-up was 14 [8-22] months. The rate of CFREM after induction therapy was 54.4% (147/270) while 21.5% (58/270) had remaining bowel urgencies after induction therapy. Among the 147 patients achieving remission after induction therapy, 12 had persistent BU (8.2%), while 62.6% (77/123) of patients with no CFREM after induction therapy did not have any BU. The agreements between BU and rectal bleeding (75.2%, κ-coefficient = 0.33±0.06) or normalization of stools frequency (67.9%,κ-coefficient = 0.35±0.05) were mild. Among the patients with persistent BU after induction therapy, only 3.7% had no endoscopic activity (MES = 0). In multivariable analyses including CFREM at week 16, persistence of BU after induction therapy was independently associated with the time to drug discontinuation (HR=2.0[1.1-3.5], p=0.016) and colectomy (HR=4.4[2.3-8.4], p<0.001), and absence of mucosal healing (OR = 5.0[1.1-24.8], p=0.046) at last follow-up. A trend was also observed regarding the association between remaining BU after induction therapy and no CFREM (OR=6.1[0.8-48.0], p=0.085) or absence of endoscopic remission (OR=2.4[0.9-6.1], p=0.077) at last follow-up. Conclusion Persistence of BU despite clinical remission is associated with higher risk of drug discontinuation due to active UC, colectomy and lower likelihood of mucosal healing. Bowel urgency should be implemented into international guidelines to define clinical remission in patients with UC.
{"title":"P386 Persistence of bowel urgency despite clinical remission after induction therapy is associated with unfavorable long-term outcomes in patients with ulcerative colitis: results from the multicenter UC-RGENCY study","authors":"A Buisson, A Amiot, M Nachury, R Altwegg, M Serrero, T Guilmoteau, X Treton, L Caillo, L Vuitton, G Bouguen, B Pereira, M Fumery","doi":"10.1093/ecco-jcc/jjad212.0516","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0516","url":null,"abstract":"Background STRIDE 2 recommendations define clinical remission as no rectal bleeding and normalization of stool frequency in patients with ulcerative colitis (UC), without including bowel urgency (BU) despite its negative impact on quality of life. In this large multicenter cohort, we aimed to assess whether the persistence of BU after induction therapy is independently associated with poor long-term outcomes in patients with UC. Methods From a multicenter retrospective study, we included consecutive UC adult patients previously exposed to at least one anti-TNF agent, with partial Mayo score (pMS) &gt; 2, who started biologics or small molecules between Jan2019 and June2022. BU was defined as a binary criterion based on the SCCAI definition. The primary endpoint was the time to drug discontinuation due to active UC. Secondary endpoints were time to relapse, time to colectomy as well as steroid-free clinical remission (pMS ≤ 2) (CFREM), endoscopic remission (CFREM + Mayo endoscopic score (MES) ≤ 1), and mucosal healing (CFREM + MES ≤ 1 + histological remission i.e. Nancy index ≤ 1) at last follow-up. Results Among 473 patients with UC, 270 were assessed for BU after induction therapy (week 16) (mean age 43.0±17.0 years-old, median UC duration 6 [3-11] years, female gender=54.0%, pancolitis=45.9%). The median follow-up was 14 [8-22] months. The rate of CFREM after induction therapy was 54.4% (147/270) while 21.5% (58/270) had remaining bowel urgencies after induction therapy. Among the 147 patients achieving remission after induction therapy, 12 had persistent BU (8.2%), while 62.6% (77/123) of patients with no CFREM after induction therapy did not have any BU. The agreements between BU and rectal bleeding (75.2%, κ-coefficient = 0.33±0.06) or normalization of stools frequency (67.9%,κ-coefficient = 0.35±0.05) were mild. Among the patients with persistent BU after induction therapy, only 3.7% had no endoscopic activity (MES = 0). In multivariable analyses including CFREM at week 16, persistence of BU after induction therapy was independently associated with the time to drug discontinuation (HR=2.0[1.1-3.5], p=0.016) and colectomy (HR=4.4[2.3-8.4], p&lt;0.001), and absence of mucosal healing (OR = 5.0[1.1-24.8], p=0.046) at last follow-up. A trend was also observed regarding the association between remaining BU after induction therapy and no CFREM (OR=6.1[0.8-48.0], p=0.085) or absence of endoscopic remission (OR=2.4[0.9-6.1], p=0.077) at last follow-up. Conclusion Persistence of BU despite clinical remission is associated with higher risk of drug discontinuation due to active UC, colectomy and lower likelihood of mucosal healing. Bowel urgency should be implemented into international guidelines to define clinical remission in patients with UC.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.0831
D C Balderramo, J Etchevers, C Fuxman, P Lubrano, M Bellicoso, G Correa, J Trakal, M R Defago, J Montero, M Toro, A Novillo, M Bonardo, N Arancibia, S Motañez, S Quines, S Huernos, A Gil, R Gonzalez, S Goncalves
Background Vedolizumab (VDZ) is a gut-selective integrin inhibitor used to treat Crohn's disease (CD). Most of the information regarding real-life data on response to VDZ has been published from North America and Europe cohorts and there is scarce information from Latin America related to effectiveness of VDZ in patients with CD. The aims of this study were: i) to describe the clinical characteristics of patients with CD who received VDZ, ii) to know in which biologic line VDZ was indicated, and iii) to evaluate the clinical response at one year and the persistence of treatment during follow-up. Methods A retrospective multicenter study was conducted in 18 Argentinean centers. We included CD adult patients (age ≥18y) who started VDZ between 01/06/2015 and 31/10/2023 and completed at least VDZ induction. Baseline demographic characteristics, response at 12 months (m), need for optimization, and treatment persistence during follow-up were assessed. Logistic regression was used to evaluate predictors for response at 12m and treatment persistence. Results A total of 113 CD patients (57% male), mean age 52 years (range 18-87 years) were included. Colonic (47%) and ileal (29%) were the most frequent CD involvement. Inflammatory (68%) was the most frequent phenotype compared to stenosing (23%) and fistulizing (9%). Perianal involvement was present in 9% of patients. VDZ was indicated as first-line in 61 (54%) patients, second-line 31 (27.4%) patients, third line 17 (15%) patients, and fourth-line 4 (3.5%) patients. At 12 m of follow-up, clinical remission was observed in 37 (32.7%) patients and clinical response in 56 (49.6%) patients. Eighteen (15.9%) patients presented a lack of response/primary failure. Adverse effects leading to VDZ discontinuation prior to 12m occurred in 2 (1.8%) patients. Mean follow-up time in those patients that achieved clinical remission/response at 12m was 23 (SD 15) m. Thirty-five (37.6%) of those patients required dose optimization and 69 (74.2%) persisted on treatment during follow-up. Male sex (OR 2.93, 95%CI 1.04-8.26) and inflammatory phenotype (OR 5.37, 95%CI 1.16-24.9) were independent predictors for clinical response/remission at 12m. VDZ in first-line (OR 3, 95%CI 1.05-8.52) and inflammatory phenotype (OR 2.96, 95%CI 1.07-8.22) were independent predictors for treatment persistence in those patients that achieved clinical remission/response at 12m. Conclusion This is the first real-life multicenter study on the effectiveness of VZD in CD in Argentina and one of the largest in Latin America. VDZ showed an effective therapeutic option in a real-life setting. A higher efficacy was observed in males, inflammatory phenotype and in biologic-naïve patients.
{"title":"P701 Evaluation of the effectiveness of vedolizumab in patients with Crohn's disease: a multicenter real-life study from Argentina","authors":"D C Balderramo, J Etchevers, C Fuxman, P Lubrano, M Bellicoso, G Correa, J Trakal, M R Defago, J Montero, M Toro, A Novillo, M Bonardo, N Arancibia, S Motañez, S Quines, S Huernos, A Gil, R Gonzalez, S Goncalves","doi":"10.1093/ecco-jcc/jjad212.0831","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0831","url":null,"abstract":"Background Vedolizumab (VDZ) is a gut-selective integrin inhibitor used to treat Crohn's disease (CD). Most of the information regarding real-life data on response to VDZ has been published from North America and Europe cohorts and there is scarce information from Latin America related to effectiveness of VDZ in patients with CD. The aims of this study were: i) to describe the clinical characteristics of patients with CD who received VDZ, ii) to know in which biologic line VDZ was indicated, and iii) to evaluate the clinical response at one year and the persistence of treatment during follow-up. Methods A retrospective multicenter study was conducted in 18 Argentinean centers. We included CD adult patients (age ≥18y) who started VDZ between 01/06/2015 and 31/10/2023 and completed at least VDZ induction. Baseline demographic characteristics, response at 12 months (m), need for optimization, and treatment persistence during follow-up were assessed. Logistic regression was used to evaluate predictors for response at 12m and treatment persistence. Results A total of 113 CD patients (57% male), mean age 52 years (range 18-87 years) were included. Colonic (47%) and ileal (29%) were the most frequent CD involvement. Inflammatory (68%) was the most frequent phenotype compared to stenosing (23%) and fistulizing (9%). Perianal involvement was present in 9% of patients. VDZ was indicated as first-line in 61 (54%) patients, second-line 31 (27.4%) patients, third line 17 (15%) patients, and fourth-line 4 (3.5%) patients. At 12 m of follow-up, clinical remission was observed in 37 (32.7%) patients and clinical response in 56 (49.6%) patients. Eighteen (15.9%) patients presented a lack of response/primary failure. Adverse effects leading to VDZ discontinuation prior to 12m occurred in 2 (1.8%) patients. Mean follow-up time in those patients that achieved clinical remission/response at 12m was 23 (SD 15) m. Thirty-five (37.6%) of those patients required dose optimization and 69 (74.2%) persisted on treatment during follow-up. Male sex (OR 2.93, 95%CI 1.04-8.26) and inflammatory phenotype (OR 5.37, 95%CI 1.16-24.9) were independent predictors for clinical response/remission at 12m. VDZ in first-line (OR 3, 95%CI 1.05-8.52) and inflammatory phenotype (OR 2.96, 95%CI 1.07-8.22) were independent predictors for treatment persistence in those patients that achieved clinical remission/response at 12m. Conclusion This is the first real-life multicenter study on the effectiveness of VZD in CD in Argentina and one of the largest in Latin America. VDZ showed an effective therapeutic option in a real-life setting. A higher efficacy was observed in males, inflammatory phenotype and in biologic-naïve patients.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.0303
P Riviere, M Dallmann-Sauer, R Enaud, T Bessissow, X Treton, M Uzzan, F Poullenot, F Zerbib, D Laharie, E Schurr
Background Limited understanding exists regarding the pathogenesis of acute severe ulcerative colitis (UC). Microorganisms are proposed as potential triggers due to the resemblances to infectious colitis and the essential role played by gut microbiota in UC-related inflammation. Our aim was to identify microbiome elements and host factors associated with acute severe UC. Methods This was a prospective study across three referral centers comparing two UC patient groups: acute severe hospitalized UC (as per Truelove and Witts criteria) and non-severe UC. We analyzed gut microbiota using 16S rRNA gene sequencing and conducted single-cell RNA-Seq on rectal biopsies in a subgroup of patients to uncover cellular subtypes and pathways involved in mucosal inflammation. We utilized whole blood RNA-Seq to investigate the host pathways involved in mediating systemic inflammation. Results Forty-one patients (23 (56%) female, median (interquartile range IQR) age 42 (34 – 57) years were included: 19 with acute severe UC and 22 with non-severe UC. Compared to patients with non-severe UC, those with acute severe UC displayed distinct gut microbiota with reduced diversity, increased Proteobacteria (Escherichia/Shigella genus), and decreased Lachnospiraceae and Ruminococcaceae. In severe cases (n=4 - 13,047 cells), single-cell RNA-Seq analysis of rectal biopsies revealed distinctive patterns compared to non-severe cases (n=5 - 18,433 cells): plasmablasts showed an altered transcriptomic profile with heightened IgG expression, and there was an expanded cluster of interleukin (IL) 26 expressing T cell population. Innate immune cells exhibited a pro-inflammatory profile marked by increased expression of the IL1B gene. In blood samples, we observed no distinct differentiation of transcriptomic profiles between severe and non-severe cases. Conclusion Our multi-omics study reveals key cellular and bacterial components in acute severe UC pathogenesis. We identified Proteobacteria, especially Escherichia coli as a potential pathobiont in acute severe UC. At the colonic level, we observed an increased IgG/IgA ratio, while both T cells and innate immune cells indicated a pro-Th17 mucosal environment. Enhanced systemic inflammation in acute severe UC was not reflected by specific changes in immune circulating cells. These insights may pave the way for future research focusing on microbiome modulation, interventions targeting plasmablasts, or nuanced inhibition of the Th17/IL-23 axis in acute severe UC.
{"title":"P173 Characterization of the gut microbiota and the colonic immune response in acute severe ulcerative colitis : the multi-omics ITAC project","authors":"P Riviere, M Dallmann-Sauer, R Enaud, T Bessissow, X Treton, M Uzzan, F Poullenot, F Zerbib, D Laharie, E Schurr","doi":"10.1093/ecco-jcc/jjad212.0303","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0303","url":null,"abstract":"Background Limited understanding exists regarding the pathogenesis of acute severe ulcerative colitis (UC). Microorganisms are proposed as potential triggers due to the resemblances to infectious colitis and the essential role played by gut microbiota in UC-related inflammation. Our aim was to identify microbiome elements and host factors associated with acute severe UC. Methods This was a prospective study across three referral centers comparing two UC patient groups: acute severe hospitalized UC (as per Truelove and Witts criteria) and non-severe UC. We analyzed gut microbiota using 16S rRNA gene sequencing and conducted single-cell RNA-Seq on rectal biopsies in a subgroup of patients to uncover cellular subtypes and pathways involved in mucosal inflammation. We utilized whole blood RNA-Seq to investigate the host pathways involved in mediating systemic inflammation. Results Forty-one patients (23 (56%) female, median (interquartile range IQR) age 42 (34 – 57) years were included: 19 with acute severe UC and 22 with non-severe UC. Compared to patients with non-severe UC, those with acute severe UC displayed distinct gut microbiota with reduced diversity, increased Proteobacteria (Escherichia/Shigella genus), and decreased Lachnospiraceae and Ruminococcaceae. In severe cases (n=4 - 13,047 cells), single-cell RNA-Seq analysis of rectal biopsies revealed distinctive patterns compared to non-severe cases (n=5 - 18,433 cells): plasmablasts showed an altered transcriptomic profile with heightened IgG expression, and there was an expanded cluster of interleukin (IL) 26 expressing T cell population. Innate immune cells exhibited a pro-inflammatory profile marked by increased expression of the IL1B gene. In blood samples, we observed no distinct differentiation of transcriptomic profiles between severe and non-severe cases. Conclusion Our multi-omics study reveals key cellular and bacterial components in acute severe UC pathogenesis. We identified Proteobacteria, especially Escherichia coli as a potential pathobiont in acute severe UC. At the colonic level, we observed an increased IgG/IgA ratio, while both T cells and innate immune cells indicated a pro-Th17 mucosal environment. Enhanced systemic inflammation in acute severe UC was not reflected by specific changes in immune circulating cells. These insights may pave the way for future research focusing on microbiome modulation, interventions targeting plasmablasts, or nuanced inhibition of the Th17/IL-23 axis in acute severe UC.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.0326
H Y Wu, C N Chen, M T Weng, C B Huang, P N Tsao, S C Wei
Background The incidence of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), has exhibited a consistent rise in recent years across Asia and Taiwan. Existing literature suggests that women with IBD may experience suboptimal perinatal outcomes. However, the specific relationship between IBD in pregnant Taiwanese women and the subsequent health outcomes of their newborns remains unclear. This study aims to meticulously examine the association between maternal IBD and perinatal outcomes using extensive and representative health databases in Taiwan. Methods We utilized four large national representative health and welfare databases: 1) Maternal and Child Health Database, 2) Birth Certificate Database, 3) National Health Insurance Database, and 4) Catastrophic Illness Database. Data spanning from 2004 to 2018 were linked using encrypted personal IDs to establish a birth cohort during this period. Mothers identified with a registered IBD diagnosis (CD: ICD 9=555, ICD 10= K50.00-K50.919; UC: ICD 9=556.0-556.6 and 556.8-556.9, ICD 10= K51.00-K51.919) in the Catastrophic Illness Database were defined as cases, with a comparison group of healthy pregnant women matched 1:10 in the same birth year and maternal age. Statistical analyses were done by chi-square tests and conditional logistic regression models. Results Among the 3,059,647 births between 2004 and 2018, 146 newborns (126 UC; 20 CD) were born by mothers with a registered IBD diagnosis (Figure 1). No statistically significant differences were observed in stillbirth, preterm birth, cesarean delivery, low birth weight, small-for-gestational-age (SGA), large-for-gestational-age (LGA), and low Apgar scores when compared to the 1,460 matched healthy mothers (Table 1). The only significant difference was observed in the incidence of hypertensive disorders of pregnancy, with a lower prevalence in the IBD group compared to the control group (4.1% vs. 13.6%; p=0.001). Multivariate conditional logistic regression analysis disclosed no significant differences in the aforementioned perinatal outcomes. Subgroup analysis demonstrated that no difference was noted between the CD and UC groups. Conclusion Through this comprehensive analysis of long-term health and welfare databases in Taiwan, we found comparable perinatal outcomes between women with IBD and matched healthy women. The birth outcomes are also improved compared with previous studies. This may be associated with advancements in medical management for IBD in recent years. Further research is needed to explore the long-term neurodevelopmental outcomes of these newborns.
{"title":"P196 Pregnancy and perinatal outcomes of Inflammatory Bowel Disease mothers in Taiwan - a nationwide health and welfare databases analysis","authors":"H Y Wu, C N Chen, M T Weng, C B Huang, P N Tsao, S C Wei","doi":"10.1093/ecco-jcc/jjad212.0326","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0326","url":null,"abstract":"Background The incidence of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), has exhibited a consistent rise in recent years across Asia and Taiwan. Existing literature suggests that women with IBD may experience suboptimal perinatal outcomes. However, the specific relationship between IBD in pregnant Taiwanese women and the subsequent health outcomes of their newborns remains unclear. This study aims to meticulously examine the association between maternal IBD and perinatal outcomes using extensive and representative health databases in Taiwan. Methods We utilized four large national representative health and welfare databases: 1) Maternal and Child Health Database, 2) Birth Certificate Database, 3) National Health Insurance Database, and 4) Catastrophic Illness Database. Data spanning from 2004 to 2018 were linked using encrypted personal IDs to establish a birth cohort during this period. Mothers identified with a registered IBD diagnosis (CD: ICD 9=555, ICD 10= K50.00-K50.919; UC: ICD 9=556.0-556.6 and 556.8-556.9, ICD 10= K51.00-K51.919) in the Catastrophic Illness Database were defined as cases, with a comparison group of healthy pregnant women matched 1:10 in the same birth year and maternal age. Statistical analyses were done by chi-square tests and conditional logistic regression models. Results Among the 3,059,647 births between 2004 and 2018, 146 newborns (126 UC; 20 CD) were born by mothers with a registered IBD diagnosis (Figure 1). No statistically significant differences were observed in stillbirth, preterm birth, cesarean delivery, low birth weight, small-for-gestational-age (SGA), large-for-gestational-age (LGA), and low Apgar scores when compared to the 1,460 matched healthy mothers (Table 1). The only significant difference was observed in the incidence of hypertensive disorders of pregnancy, with a lower prevalence in the IBD group compared to the control group (4.1% vs. 13.6%; p=0.001). Multivariate conditional logistic regression analysis disclosed no significant differences in the aforementioned perinatal outcomes. Subgroup analysis demonstrated that no difference was noted between the CD and UC groups. Conclusion Through this comprehensive analysis of long-term health and welfare databases in Taiwan, we found comparable perinatal outcomes between women with IBD and matched healthy women. The birth outcomes are also improved compared with previous studies. This may be associated with advancements in medical management for IBD in recent years. Further research is needed to explore the long-term neurodevelopmental outcomes of these newborns.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.0244
B Verstockt, S Vermeire, L Peyrin-Biroulet, A Yarur, R Panaccione, R Mosig, F Cataldi, S Danese
Background NLRX1 activation reduces inflammation by decreasing oxidative stress and altering cellular metabolism within multiple cell types implicated in ulcerative colitis (UC). Colitis animal models demonstrated reduced disease severity and a phase 1b clinical trial showed signs of rapid symptom and endoscopic improvement in patients with active UC.1, 2 Abdominal pain driven by visceral hypersensitivity may persist in patients even after inflammation has resolved, negatively affecting their quality of life.3, 4 Therapeutic agents which address inflammation, epithelial healing, and visceral hypersensitivity concurrently may provide greater symptomatic relief and improved quality of life as many patients, even in remission, still complain of abdominal pain. We here describe the effects of oral NX-13 in a rat model of visceral hypersensitivity. Methods Rats (n=8) were dosed daily for a period of 3 days with NX-13 or vehicle. Under anesthesia, electrodes were positioned to monitor oblique abdominal muscle contraction and a colonic balloon catheter was inserted intra-anally. Visceral pain was assessed at baseline and 3 h post lipopolysaccharide injection (1 mg/kg subcutaneous) through measuring of visceromotor response (VMR) via electromyogram (EMG) recording and visual assessment of abdominal withdrawal reflex (AWR). Data are represented as median (IQR) and statistical significance determined by non-parametric Mann-Whitney U test. Results Compared to the vehicle control, oral NX-13 delayed the onset of muscle contraction in response to colonic distension in LPS-treated rats. Further, NX-13 treated rats experienced reduced contraction intensity and reduced sustained abdominal muscle contraction period compared to the vehicle control. Specifically, NX-13 decreased the number of AWR during colonic expansion compared to the control group (p=0.01, Fig1A). Moreover, NX-13 desensitized the VMR response by numerically increasing the minimum volume of the colonic distension balloon required to induce significant VMR. The mean minimum volume of water injected required to induce significant VMR increased 23%, from 650 μL in the vehicle group to 800 μL in the NX-13 treated rats (p=0.16, Fig1B). Lastly, NX-13 visually reduced the maximum abdominal EMG amplitude during colonic distention (p=0.19, Fig1C). Conclusion Adequate management of persistent pain in IBD patients with or without active bowel inflammation remains an unmet need in the treatment of IBD. The potential for NX-13 to specifically reduce visceral hypersensitivity and abdominal pain will be evaluated further in the ongoing phase 2 human NEXUS trial in patients with UC. 1Leber et al. J Immunol 203(12) 2Peyrin-Biroulet et al. JCC (17)Supp 3Abreu et al. JCC (14)Supp 4Wils et al. J Clin Med 11(15)
{"title":"P114 Role of NLRX1 Agonist NX-13 in Reducing Visceral Hypersensitivity in Preclinical Gastrointestinal Inflammation","authors":"B Verstockt, S Vermeire, L Peyrin-Biroulet, A Yarur, R Panaccione, R Mosig, F Cataldi, S Danese","doi":"10.1093/ecco-jcc/jjad212.0244","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0244","url":null,"abstract":"Background NLRX1 activation reduces inflammation by decreasing oxidative stress and altering cellular metabolism within multiple cell types implicated in ulcerative colitis (UC). Colitis animal models demonstrated reduced disease severity and a phase 1b clinical trial showed signs of rapid symptom and endoscopic improvement in patients with active UC.1, 2 Abdominal pain driven by visceral hypersensitivity may persist in patients even after inflammation has resolved, negatively affecting their quality of life.3, 4 Therapeutic agents which address inflammation, epithelial healing, and visceral hypersensitivity concurrently may provide greater symptomatic relief and improved quality of life as many patients, even in remission, still complain of abdominal pain. We here describe the effects of oral NX-13 in a rat model of visceral hypersensitivity. Methods Rats (n=8) were dosed daily for a period of 3 days with NX-13 or vehicle. Under anesthesia, electrodes were positioned to monitor oblique abdominal muscle contraction and a colonic balloon catheter was inserted intra-anally. Visceral pain was assessed at baseline and 3 h post lipopolysaccharide injection (1 mg/kg subcutaneous) through measuring of visceromotor response (VMR) via electromyogram (EMG) recording and visual assessment of abdominal withdrawal reflex (AWR). Data are represented as median (IQR) and statistical significance determined by non-parametric Mann-Whitney U test. Results Compared to the vehicle control, oral NX-13 delayed the onset of muscle contraction in response to colonic distension in LPS-treated rats. Further, NX-13 treated rats experienced reduced contraction intensity and reduced sustained abdominal muscle contraction period compared to the vehicle control. Specifically, NX-13 decreased the number of AWR during colonic expansion compared to the control group (p=0.01, Fig1A). Moreover, NX-13 desensitized the VMR response by numerically increasing the minimum volume of the colonic distension balloon required to induce significant VMR. The mean minimum volume of water injected required to induce significant VMR increased 23%, from 650 μL in the vehicle group to 800 μL in the NX-13 treated rats (p=0.16, Fig1B). Lastly, NX-13 visually reduced the maximum abdominal EMG amplitude during colonic distention (p=0.19, Fig1C). Conclusion Adequate management of persistent pain in IBD patients with or without active bowel inflammation remains an unmet need in the treatment of IBD. The potential for NX-13 to specifically reduce visceral hypersensitivity and abdominal pain will be evaluated further in the ongoing phase 2 human NEXUS trial in patients with UC. 1Leber et al. J Immunol 203(12) 2Peyrin-Biroulet et al. JCC (17)Supp 3Abreu et al. JCC (14)Supp 4Wils et al. J Clin Med 11(15)","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.0827
M Belkovsky, B Cohen, J Sommovilla, T Hull, S Holubar
Background Non-conventional strictureplasties, specifically the Finney and Michelassi technique, are bowel-preserving surgical techniques for diffuse jejunoileal Crohn’s Disease (CD). We investigated the association of biologic use during non-conventional strictureplasty for Crohn's jejunoileitis and its short- and long-term outcomes. Methods We conducted a retrospective review of all patients with CD who underwent non-conventional strictureplasty at our centre, e.g., side-to-side antiperistaltic strictureplasty (SSAS) according to the Finney or modified Finney technique, or side-to-side isoperistaltic (SSIS) according to the Michelassi or modified Michelassi techniques from January 2000 to October 2022. Patients were categorized into BIO and NoBIO groups based on their uninterrupted use of biologics until the moment of surgery. Our outcomes of interest were: (a)30-day complications; and (b)surgical recurrence. Statistical analysis was performed using R version 4.3.1. Results A total of 71 patients underwent non-conventional strictureplasty: 80 SSAS and 14 SSIS. Group 1 had 17 patients in which 15 SSAS and 3 SSIS were performed. Group 2 had 54 patients in which 65 SSAS and 11 SSIS were performed. Most patients also underwent concurrent Heineke-Mikulicz strictureplasty in 49 patients (69%) and concurrent small bowel resection in 53 patients (74.6%). The patients in the BIO and NoBIO groups had similar baseline characteristics (Table 1). No differences were observed in perioperative outcomes (Table 2). No difference was observed when comparing surgical recurrence rates, but a longer median time to recurrence was observed in the BIO group (4.7 vs. 4.4 years, p=0.004). Conclusion Biologic use at the time of non-conventional strictureplasty for diffuse jejunoileal Crohn’s disease is safe and is associated with a longer median time to recurrence.
{"title":"P697 Short- and long-term outcomes following biologic use before non-conventional stricureplasty for Crohn’s Jejunoileitis","authors":"M Belkovsky, B Cohen, J Sommovilla, T Hull, S Holubar","doi":"10.1093/ecco-jcc/jjad212.0827","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0827","url":null,"abstract":"Background Non-conventional strictureplasties, specifically the Finney and Michelassi technique, are bowel-preserving surgical techniques for diffuse jejunoileal Crohn’s Disease (CD). We investigated the association of biologic use during non-conventional strictureplasty for Crohn's jejunoileitis and its short- and long-term outcomes. Methods We conducted a retrospective review of all patients with CD who underwent non-conventional strictureplasty at our centre, e.g., side-to-side antiperistaltic strictureplasty (SSAS) according to the Finney or modified Finney technique, or side-to-side isoperistaltic (SSIS) according to the Michelassi or modified Michelassi techniques from January 2000 to October 2022. Patients were categorized into BIO and NoBIO groups based on their uninterrupted use of biologics until the moment of surgery. Our outcomes of interest were: (a)30-day complications; and (b)surgical recurrence. Statistical analysis was performed using R version 4.3.1. Results A total of 71 patients underwent non-conventional strictureplasty: 80 SSAS and 14 SSIS. Group 1 had 17 patients in which 15 SSAS and 3 SSIS were performed. Group 2 had 54 patients in which 65 SSAS and 11 SSIS were performed. Most patients also underwent concurrent Heineke-Mikulicz strictureplasty in 49 patients (69%) and concurrent small bowel resection in 53 patients (74.6%). The patients in the BIO and NoBIO groups had similar baseline characteristics (Table 1). No differences were observed in perioperative outcomes (Table 2). No difference was observed when comparing surgical recurrence rates, but a longer median time to recurrence was observed in the BIO group (4.7 vs. 4.4 years, p=0.004). Conclusion Biologic use at the time of non-conventional strictureplasty for diffuse jejunoileal Crohn’s disease is safe and is associated with a longer median time to recurrence.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.0609
S Choi, J H Ji, S J Park, J J Park, J H Cheon, T I Kim, J Park
Background The association of intestinal Behçet’s disease (BD) with the risk of hematologic malignancy is still unclear. We aimed to assess the prevalence and determine risk factors of hematologic malignancy in intestinal BD. Methods Using a cohort of patients with intestinal BD between 1997 and 2021, the prevalence and risk factors of hematologic malignancy were analysed by logistic regression analysis at inflammatory bowel disease centre of Severance Hospital, Seoul, Korea. Results Among 780 intestinal BD patients, 23 patients developed hematologic malignancy. Myelodysplastic syndrome (MDS) (n=12) was the most common hematologic malignancy, followed by aplastic anemia (AA) (n=7), leukemia (n=2), and lymphoma (n=2). Eight patients had developed hematologic malignancy before their intestinal BD diagnosis and 15 patients developed hematologic malignancy after their intestinal BD diagnosis. Of the 772 patients without previous hematologic malignancy, patients smoking history (p-value 0.019, odds ratio [OR] 49.513, 95% confidence interval [CI] 1.925-1273.4), history of at least one emergency room (ER) visit (p-value 0.025, OR 26.360, CI 1.501-462.92), and albumin lower than 3.3g/dL (p-value 0.046, OR 603.013, CI 0.108-328191.23) at diagnosis were positively associated with subsequent hematologic malignancy. Body mass index (BMI) (p-value 0.030, OR 0.569, CI 0.342-0.947) was negatively associated with hematologic malignancy. Conclusion The physicians who care for intestinal BD patients with risk factors should be aware and provide careful monitoring of the elevated risk of hematologic malignancy.
{"title":"P479 The prevalence and risk factors of hematologic malignancy in patients with intestinal Behçet’s disease","authors":"S Choi, J H Ji, S J Park, J J Park, J H Cheon, T I Kim, J Park","doi":"10.1093/ecco-jcc/jjad212.0609","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0609","url":null,"abstract":"Background The association of intestinal Behçet’s disease (BD) with the risk of hematologic malignancy is still unclear. We aimed to assess the prevalence and determine risk factors of hematologic malignancy in intestinal BD. Methods Using a cohort of patients with intestinal BD between 1997 and 2021, the prevalence and risk factors of hematologic malignancy were analysed by logistic regression analysis at inflammatory bowel disease centre of Severance Hospital, Seoul, Korea. Results Among 780 intestinal BD patients, 23 patients developed hematologic malignancy. Myelodysplastic syndrome (MDS) (n=12) was the most common hematologic malignancy, followed by aplastic anemia (AA) (n=7), leukemia (n=2), and lymphoma (n=2). Eight patients had developed hematologic malignancy before their intestinal BD diagnosis and 15 patients developed hematologic malignancy after their intestinal BD diagnosis. Of the 772 patients without previous hematologic malignancy, patients smoking history (p-value 0.019, odds ratio [OR] 49.513, 95% confidence interval [CI] 1.925-1273.4), history of at least one emergency room (ER) visit (p-value 0.025, OR 26.360, CI 1.501-462.92), and albumin lower than 3.3g/dL (p-value 0.046, OR 603.013, CI 0.108-328191.23) at diagnosis were positively associated with subsequent hematologic malignancy. Body mass index (BMI) (p-value 0.030, OR 0.569, CI 0.342-0.947) was negatively associated with hematologic malignancy. Conclusion The physicians who care for intestinal BD patients with risk factors should be aware and provide careful monitoring of the elevated risk of hematologic malignancy.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.0158
Y Yasutomi, A Chiba, K Haga, G Murayama, A Makiyama, T Kuga, A Nagahara, T Nagaishi, S Miyake
Background It is known that the mucosal-associated invariant T (MAIT) cells are the innate-like T cells that are restricted by the major histocompatibility complex-related molecule 1 (MR1), and that these cells express a semi-invariant T cell receptor. We have previously reported that the activation status of the circulating MAIT cells in patients with Ulcerative Colitis (UC) is associated with disease activity, and these cells infiltrate the inflamed colonic mucosa. These findings imply that MAIT cells are involved in the pathogenesis of Inflammatory Bowel Disease (IBD). However, the role of MAIT cells in the setting of IBD has not been revealed. Therefore, we investigated the role of MAIT cells in an animal model of UC. Methods To this end, we utilized MR1 deficient mice (MR1-/-), which lack MAIT cells, and isobutyl 6-formyl pterin (i6-FP), which is a synthetic antagonistic MR1 ligand. MR1-/- on the C57BL/6 background, their littermate wild-type controls, and C57BL/6 mice were sensitized by rectal administration of oxazolone to induce colitis. These were then administered an oral i6-FP. Splenocytes (SPL) and colonic lamina propria lymphocytes (LPL) were isolated from mice receiving i6-FP to measure cytokine production. MR1-/-, i6-FP-treated mice and their controls were orally administered FITC-dextran to analyze intestinal permeability. The peripheral blood mononuclear cells (PBMC) from the patients with UC were also isolated to study the effect of i6-FP on cytokine production by MAIT cells. Results MR1 deficiency or i6-FP treatment resulted in reduced severity of oxazolone-induced colitis. Mice treated with i6-FP resulted in reduced MAIT cell production of pro-inflammatory cytokines such as IFN-g and TNF in both SPL and colonic LPL. Similar results were also observed in PBMC isolated from the patients with UC when incubated with i6-FP. Although MR1 deficiency resulted in increased intestinal permeability, i6-FP administration did not affect gut integrity in mice. Conclusion The current studies indicate that MAIT cells have a pathogenic role in colitis and suppressing activation of these cells may reduce the severity of colitis without affecting gut integrity. Thus, MAIT cells may be potential therapeutic targets for IBD including UC.
{"title":"P028 A pathogenic role of activated mucosal-associated invariant T cells in an animal model of Inflammatory Bowel Disease","authors":"Y Yasutomi, A Chiba, K Haga, G Murayama, A Makiyama, T Kuga, A Nagahara, T Nagaishi, S Miyake","doi":"10.1093/ecco-jcc/jjad212.0158","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0158","url":null,"abstract":"Background It is known that the mucosal-associated invariant T (MAIT) cells are the innate-like T cells that are restricted by the major histocompatibility complex-related molecule 1 (MR1), and that these cells express a semi-invariant T cell receptor. We have previously reported that the activation status of the circulating MAIT cells in patients with Ulcerative Colitis (UC) is associated with disease activity, and these cells infiltrate the inflamed colonic mucosa. These findings imply that MAIT cells are involved in the pathogenesis of Inflammatory Bowel Disease (IBD). However, the role of MAIT cells in the setting of IBD has not been revealed. Therefore, we investigated the role of MAIT cells in an animal model of UC. Methods To this end, we utilized MR1 deficient mice (MR1-/-), which lack MAIT cells, and isobutyl 6-formyl pterin (i6-FP), which is a synthetic antagonistic MR1 ligand. MR1-/- on the C57BL/6 background, their littermate wild-type controls, and C57BL/6 mice were sensitized by rectal administration of oxazolone to induce colitis. These were then administered an oral i6-FP. Splenocytes (SPL) and colonic lamina propria lymphocytes (LPL) were isolated from mice receiving i6-FP to measure cytokine production. MR1-/-, i6-FP-treated mice and their controls were orally administered FITC-dextran to analyze intestinal permeability. The peripheral blood mononuclear cells (PBMC) from the patients with UC were also isolated to study the effect of i6-FP on cytokine production by MAIT cells. Results MR1 deficiency or i6-FP treatment resulted in reduced severity of oxazolone-induced colitis. Mice treated with i6-FP resulted in reduced MAIT cell production of pro-inflammatory cytokines such as IFN-g and TNF in both SPL and colonic LPL. Similar results were also observed in PBMC isolated from the patients with UC when incubated with i6-FP. Although MR1 deficiency resulted in increased intestinal permeability, i6-FP administration did not affect gut integrity in mice. Conclusion The current studies indicate that MAIT cells have a pathogenic role in colitis and suppressing activation of these cells may reduce the severity of colitis without affecting gut integrity. Thus, MAIT cells may be potential therapeutic targets for IBD including UC.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.1219
G Bröms, A Forss, J Eriksson, M Linder, C Eriksson, J Askling, J Halfvarson, J F Ludvigsson, O Olen
Background Studies from mainly before the wide use of targeted therapies and guidelines for thromboprophylaxis indicate that patients with inflammatory bowel disease (IBD) are at a doubled risk of venous thromboembolism (VTE). We studied the risk of VTE in a modern-day cohort of patients with IBD, overall and in subgroups of disease characteristics. Methods Using Swedish healthcare registers, we identified a nationwide population-based cohort of 55,252 patients with incident IBD between 2007 and 2021 with a median follow-up time of 6.5 years. Patients were matched by age, sex, calendar year and county of residence with up to ten reference individuals from the general population (N=536,067). The primary outcome was VTE, including pulmonary embolism and deep vein thrombosis. Incidence rates per 1,000 person-years and hazard ratios (HR) were calculated for IBD in general and according to disease subtype, sex, age and disease characteristics at diagnosis. HRs stratified by matching variables (model 1) and additionally adjusted for comorbidities and socioeconomic factors (model 2) were estimated by using Cox regression. Results The incidence rate of VTE among patients with IBD was 5.03 per 1,000 person-years compared with 2.34 per 1,000 person-years among reference individuals (Table 1). This corresponded to a doubled incidence of VTE (HR=2.18, 95% confidence interval (CI)=2.07-2.29, model 1). Adjusting further for covariates in model 2 had only minor effects on the HR. The HR was consistent across IBD subtypes and sex. The relative risk was higher for those with younger age (18-39 years) at IBD diagnosis (HR 2.52, 95% CI: 2.22-2.83) with a risk difference of 1.25 per 1,000 person-years. The IR, 10.64 per 1,000 person-years, and risk difference, 5.42 per 1,000 person-years, was the highest for those with elderly onset (≥60 years) IBD. There was a stronger association for those with extensive ulcerative colitis (E3), primary sclerosing cholangitis, extraintestinal manifestations and perianal disease. HRs for VTE were persistently elevated across follow-up time, but was higher during the first year of follow-up (Figure 1). Conclusion The risk of VTE was doubled in these modern-day data and remained elevated across follow-up time. Disease characteristics associated with higher inflammatory burden at diagnosis and older age are markers of increased risk. This underscores the importance of continuous vigilance and individual assessment of risk factors for VTE in patients with IBD.
{"title":"P1089 Disease characteristics at time of diagnosis of adult onset inflammatory bowel disease and the risk of venous thromboembolism in the modern era – A Swedish nationwide cohort study 2007-2021","authors":"G Bröms, A Forss, J Eriksson, M Linder, C Eriksson, J Askling, J Halfvarson, J F Ludvigsson, O Olen","doi":"10.1093/ecco-jcc/jjad212.1219","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.1219","url":null,"abstract":"Background Studies from mainly before the wide use of targeted therapies and guidelines for thromboprophylaxis indicate that patients with inflammatory bowel disease (IBD) are at a doubled risk of venous thromboembolism (VTE). We studied the risk of VTE in a modern-day cohort of patients with IBD, overall and in subgroups of disease characteristics. Methods Using Swedish healthcare registers, we identified a nationwide population-based cohort of 55,252 patients with incident IBD between 2007 and 2021 with a median follow-up time of 6.5 years. Patients were matched by age, sex, calendar year and county of residence with up to ten reference individuals from the general population (N=536,067). The primary outcome was VTE, including pulmonary embolism and deep vein thrombosis. Incidence rates per 1,000 person-years and hazard ratios (HR) were calculated for IBD in general and according to disease subtype, sex, age and disease characteristics at diagnosis. HRs stratified by matching variables (model 1) and additionally adjusted for comorbidities and socioeconomic factors (model 2) were estimated by using Cox regression. Results The incidence rate of VTE among patients with IBD was 5.03 per 1,000 person-years compared with 2.34 per 1,000 person-years among reference individuals (Table 1). This corresponded to a doubled incidence of VTE (HR=2.18, 95% confidence interval (CI)=2.07-2.29, model 1). Adjusting further for covariates in model 2 had only minor effects on the HR. The HR was consistent across IBD subtypes and sex. The relative risk was higher for those with younger age (18-39 years) at IBD diagnosis (HR 2.52, 95% CI: 2.22-2.83) with a risk difference of 1.25 per 1,000 person-years. The IR, 10.64 per 1,000 person-years, and risk difference, 5.42 per 1,000 person-years, was the highest for those with elderly onset (≥60 years) IBD. There was a stronger association for those with extensive ulcerative colitis (E3), primary sclerosing cholangitis, extraintestinal manifestations and perianal disease. HRs for VTE were persistently elevated across follow-up time, but was higher during the first year of follow-up (Figure 1). Conclusion The risk of VTE was doubled in these modern-day data and remained elevated across follow-up time. Disease characteristics associated with higher inflammatory burden at diagnosis and older age are markers of increased risk. This underscores the importance of continuous vigilance and individual assessment of risk factors for VTE in patients with IBD.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.0350
O M Nardone, G Calabrese, M Allocca, F Caprioli, E D'Alessandro, M Fantini, S Onali, A Orlando, A Rispo, E Savarino, A Soriano, A Variola, F Castiglione
Background As an objective endpoint in IBD Disease-Modification Trials, measures of disability and health-related quality of life have been proposed. IBD-DISK is an easy-to-use, and self-administered analogic visual tool designed for assessing disability. However, successful dissemination of this tool will require a cultural adaptation and translation process. To date, the IBD-Disk has not been validated in Italian clinical practice. Hence, we aimed to validate the IBD-Disk in an Italian population-based cohort according to the COSMIN recommendations. Methods The IBD-Disk italian translation and validation study was a cross-sectional multicentre study conducted in 8 Italian IBD referral centres. After forward-backward translation into Italian, patients were consecutively recruited from February 2023 to October 2023. Patients completed the following questionnaires: IBD-Disk (at baseline, T0, and after seven days, T1) and IBD-Disability Index (IBD-DI) for disability, IBDQ-32, and SF-36 for quality of life. Validation included assessment of validity, reproducibility, internal consistency. We further investigated the correlation between IBD-Disk and IBD activity and clinical factors associated with IBD-Disk. Results At baseline, 513 patients (237,46.2% CD; 276,53.8% UC) completed the IBD-Disk[Table.1]. Internal consistency was excellent with a Cronbach’s α of 0.93. The intraclass correlation coefficient (ICC) was 0.94 for test-retest (T0 and T1) (p< 0.001). To evaluate construct validity, the IBD-Disk was compared with the IBD-DI, revealing a significant positive correlation (r = 0.70; p < 0.001). Furthermore, it exhibited a positive correlation with both IBDQ-32(r=0.82, p< 0.001) and SF-36(r=0.093, p= 0.035). The overall IBD-Disk median score was 32(12-52), with 219(42.7%) reporting moderate-to-severe disability (IBD-DISK ≥ 40). The IBD-Disk score was significantly higher in patients with active CD disease based on HBI ≥ 5 compared to patients with inactive disease(p < 0.001). Similarly, for UC, patients with active disease, measured with a partial Mayo score ≥2, showed a higher IBD-DISK score than those in clinical remission[Fig.1]. Additionally, moderate-to-severe disability significantly increased in female [OR =2.83; 95% CI(1,97-4,07)] and in patients with active extraintestinal manifestations [OR = 1,71; 95%CI(1,23-2,81) p=0.04]. Conclusion This study validated the IBD-Disk in a large cohort of Italian IBD patients, demonstrating that it is a valid, reliable and responsive tool for quantifying disability. This validation enables the broad implementation of IBD-DISK across Italy, facilitating its integration into the daily clinical management of IBD patients.
{"title":"P220 IBD-Disk: italian translation and validation in a population-based cohort","authors":"O M Nardone, G Calabrese, M Allocca, F Caprioli, E D'Alessandro, M Fantini, S Onali, A Orlando, A Rispo, E Savarino, A Soriano, A Variola, F Castiglione","doi":"10.1093/ecco-jcc/jjad212.0350","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0350","url":null,"abstract":"Background As an objective endpoint in IBD Disease-Modification Trials, measures of disability and health-related quality of life have been proposed. IBD-DISK is an easy-to-use, and self-administered analogic visual tool designed for assessing disability. However, successful dissemination of this tool will require a cultural adaptation and translation process. To date, the IBD-Disk has not been validated in Italian clinical practice. Hence, we aimed to validate the IBD-Disk in an Italian population-based cohort according to the COSMIN recommendations. Methods The IBD-Disk italian translation and validation study was a cross-sectional multicentre study conducted in 8 Italian IBD referral centres. After forward-backward translation into Italian, patients were consecutively recruited from February 2023 to October 2023. Patients completed the following questionnaires: IBD-Disk (at baseline, T0, and after seven days, T1) and IBD-Disability Index (IBD-DI) for disability, IBDQ-32, and SF-36 for quality of life. Validation included assessment of validity, reproducibility, internal consistency. We further investigated the correlation between IBD-Disk and IBD activity and clinical factors associated with IBD-Disk. Results At baseline, 513 patients (237,46.2% CD; 276,53.8% UC) completed the IBD-Disk[Table.1]. Internal consistency was excellent with a Cronbach’s α of 0.93. The intraclass correlation coefficient (ICC) was 0.94 for test-retest (T0 and T1) (p&lt; 0.001). To evaluate construct validity, the IBD-Disk was compared with the IBD-DI, revealing a significant positive correlation (r = 0.70; p &lt; 0.001). Furthermore, it exhibited a positive correlation with both IBDQ-32(r=0.82, p&lt; 0.001) and SF-36(r=0.093, p= 0.035). The overall IBD-Disk median score was 32(12-52), with 219(42.7%) reporting moderate-to-severe disability (IBD-DISK ≥ 40). The IBD-Disk score was significantly higher in patients with active CD disease based on HBI ≥ 5 compared to patients with inactive disease(p &lt; 0.001). Similarly, for UC, patients with active disease, measured with a partial Mayo score ≥2, showed a higher IBD-DISK score than those in clinical remission[Fig.1]. Additionally, moderate-to-severe disability significantly increased in female [OR =2.83; 95% CI(1,97-4,07)] and in patients with active extraintestinal manifestations [OR = 1,71; 95%CI(1,23-2,81) p=0.04]. Conclusion This study validated the IBD-Disk in a large cohort of Italian IBD patients, demonstrating that it is a valid, reliable and responsive tool for quantifying disability. This validation enables the broad implementation of IBD-DISK across Italy, facilitating its integration into the daily clinical management of IBD patients.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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