scholarly journals Analysis of systemic epigenetic alterations in inflammatory bowel disease: defining geographical, genetic, and immune-inflammatory influences on the circulating methylome

2021 ◽  
Author(s):  
Rahul Kalla ◽  
Alex Adams ◽  
Jan Nowak ◽  
Daniel Bergemalm ◽  
Simen Vatn ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Epigenetic Alterations ◽  
Cell Of Origin ◽  
Gene Environment ◽  
Dna Methylation Profile ◽  
Activation Response ◽  
Inflammatory Bowel ◽  
Treatment Escalation

Abstract Gene-environment interactions play a pivotal role in the pathogenesis of Inflammatory Bowel Disease (IBD). Using the IBD Character inception cohort (295 controls, 154 CD, 161 UC, 28 IBD-U) we confirm the presence of a highly characteristic DNA methylation profile in peripheral blood implicating 137 differentially methylated positions (DMP) in IBD, including VMP1/MIR21 (p = 9.11×10− 15) and RPS6KA2 (6.43×10− 13); with consistency seen across Scandinavia and UK. Cell of origin analysis preferentially implicated the monocyte lineage. Dysregulated loci demonstrate strong genetic influence, notably VMP1 (p = 1.53×10− 15). Age acceleration is seen in IBD (coefficient 0.94, p < 2.2x10− 16). Several immuno-active genes demonstrated highly significant correlations between methylation and gene expression in IBD, in particular OSM: IBD r -0.32, p 3.64×10− 7 vs. non-IBD r -0.14, p = 0.77). Multi-omic integration of methylome, genome and transcriptome also implicate specific pathways that associate with immune activation, response and regulation at disease inception. At follow up, a signature of 3 DMPs (TAP1, TESPA1, RPTOR) associated with treatment escalation to biological agents or surgery (hazard ratio of 5.19 (CI:2.14–12.56, logrank p = 9.70×10− 4).

Epigenetic Alterations at Diagnosis Predict Susceptibility, Prognosis and Treatment Escalation in Inflammatory Bowel Disease and IBD Character

2017 ◽  
Vol 152 (5) ◽  
pp. S565
Author(s):  
Rahul Kalla ◽  
Alex Adams ◽  
Simen Vatn ◽  
Ferdinando Bonfiglio ◽  
Elaine Nimmo ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Epigenetic Alterations ◽  
Inflammatory Bowel ◽  
Treatment Escalation

scholarly journals P56 Two year follow up of children with inflammatory bowel disease (IBD) treated with Vedolizumab and Ustekinumab

2021 ◽  
Author(s):  
Roxana Mardare ◽  
Natasha Burgess ◽  
Dominic Studart ◽  
Protima Deb ◽  
Marco Gasparetto ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Inflammatory Bowel

scholarly journals Utility of routinely collected electronic health records data to support effectiveness evaluations in inflammatory bowel disease: a pilot study of tofacitinib

2021 ◽  
Vol 28 (1) ◽  
pp. e100337
Author(s):  
Vivek Ashok Rudrapatna ◽  
Benjamin Scott Glicksberg ◽  
Atul Janardhan Butte
Keyword(s):  
Inflammatory Bowel Disease ◽  
Pilot Study ◽  
Disease Activity ◽  
Real World ◽  
Bowel Disease ◽  
P Value ◽  
Health Records ◽  
Real World Evidence ◽  
Inflammatory Bowel

ObjectivesElectronic health records (EHR) are receiving growing attention from regulators, biopharmaceuticals and payors as a potential source of real-world evidence. However, their suitability for the study of diseases with complex activity measures is unclear. We sought to evaluate the use of EHR data for estimating treatment effectiveness in inflammatory bowel disease (IBD), using tofacitinib as a use case.MethodsRecords from the University of California, San Francisco (6/2012 to 4/2019) were queried to identify tofacitinib-treated IBD patients. Disease activity variables at baseline and follow-up were manually abstracted according to a preregistered protocol. The proportion of patients meeting the endpoints of recent randomised trials in ulcerative colitis (UC) and Crohn’s disease (CD) was assessed.Results86 patients initiated tofacitinib. Baseline characteristics of the real-world and trial cohorts were similar, except for universal failure of tumour necrosis factor inhibitors in the former. 54% (UC) and 62% (CD) of patients had complete capture of disease activity at baseline (month −6 to 0), while only 32% (UC) and 69% (CD) of patients had complete follow-up data (month 2 to 8). Using data imputation, we estimated the proportion achieving the trial primary endpoints as being similar to the published estimates for both UC (16%, p value=0.5) and CD (38%, p-value=0.8).Discussion/ConclusionThis pilot study reproduced trial-based estimates of tofacitinib efficacy despite its use in a different cohort but revealed substantial missingness in routinely collected data. Future work is needed to strengthen EHR data and enable real-world evidence in complex diseases like IBD.

scholarly journals A186 OLDER AGE IS ASSOCIATED WITH INCREASED EXTRAINTESTINAL MANIFESTATIONS IN INFLAMMATORY BOWEL DISEASE

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 201-202
Author(s):  
Z Chattha ◽  
R Chattha ◽  
S Reza ◽  
M Moradshahi ◽  
M Fadida ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Regression Analysis ◽  
Bowel Disease ◽  
Multivariate Regression Analysis ◽  
Older Age ◽  
Extraintestinal Manifestations ◽  
Forward Selection ◽  
Increased Risk ◽  
Inflammatory Bowel

Abstract Background The relationship between older age and extraintestinal manifestations (EIMs) in patients with inflammatory bowel disease (IBD) remains unknown. Aims This study aims to determine whether older age is associated with increased risk of EIMs in IBD patients. Methods This was a retrospective study of IBD patients seen at the McMaster University Medical Centre, in Hamilton, ON, Canada from 2012–2020. Patients were identified to have the primary outcome of interest if their gastroenterologist documented the presence of any EIM either during the baseline assessment or during the period of follow up. The independent variable, age at start of follow-up, was dichotomized into two categories age &gt;=40 vs. &lt;40.Prior knowledge in combination with forward selection was used to develop a logistic regression model. The variables utilized for the forward selection model included gender, disease duration, and current biologic use. Results A total of 995 IBD patients (625 with CD) were considered for the regression analysis, all for whom the EIM status was recorded. Out of the 995 patients, 270 patients reported at least one EIM – 99 with arthritis/arthralgia, 79 with dermatologic manifestations, 16 with ophthalmic manifestations, 30 with liver manifestations, and 116 with other EIMs. A univariate regression analysis foundincreased odds of EIMs in older patientsas compared to younger patients (odds ratio (OR) 1.41 (95% CI, 1.05 – 1.89)). In the multivariate regression analysis, current biologic use was found to have a significant relationship with odds of having EIMs (OR 1.49; 95% CI, 1.06 – 2.09). After adjustment for biologic use, patients aged 40 or over had 1.46 times higher odds of having EIMs (95% CI 1.03 – 2.05). A sub-analysis of individual EIM categoriesdid not show a significant association with older age. Conclusions Older age is associated with increased risk of EIMs in IBD patients. Patients with EIMs were also more likely to be treated with biological therapies. Clinicians should inquire about the presence of EIMs in older IBD patients. Funding Agencies None

scholarly journals Open access follow-up for inflammatory bowel disease: A pragmatic randomised trial and costeffectiveness study

2000 ◽  
Vol 118 (4) ◽  
pp. A722
Author(s):  
Krishnaraj Ragunath ◽  
John G. Williams ◽  
Wai-Yee Cheung ◽  
Mesbahur M. Rahman ◽  
Ian T. Russell ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Open Access ◽  
Bowel Disease ◽  
Randomised Trial ◽  
Inflammatory Bowel

scholarly journals P088 Mucosal CD103+ CD4+ and CD103+CD8+ T-cell subsets in the gut of inflammatory bowel disease patients at diagnosis and during follow-up

2018 ◽  
Vol 12 (supplement_1) ◽  
pp. S137-S138
Author(s):  
B Roosenboom ◽  
C Smids ◽  
P Wahab ◽  
M Groenen ◽  
E Van Koolwijk ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cell ◽  
Bowel Disease ◽  
Cd8 T Cell ◽  
T Cell Subsets ◽  
Inflammatory Bowel

Anti-Tumor Necrosis Factor-Alpha Withdrawal in Children With Inflammatory Bowel Disease in Endoscopic and Histologic Remission

2021 ◽  
Author(s):  
Luca Scarallo ◽  
Giulia Bolasco ◽  
Jacopo Barp ◽  
Martina Bianconi ◽  
Monica di Paola ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Treatment Withdrawal ◽  
Clinical Relapse ◽  
Necrosis Factor Alpha ◽  
Mayo Score ◽  
Endoscopic Score ◽  
Inflammatory Bowel ◽  
Factor Alpha

Abstract Background The aim of the present study was to investigate outcomes of anti-TNF-alpha (ATA) withdrawal in selected pediatric patients with inflammatory bowel disease who achieved clinical remission and mucosal and histological healing (MH and HH). Methods A retrospective analysis was performed on children and adolescents affected by Crohn disease (CD) and ulcerative colitis (UC) who were followed up at 2 tertiary referral centers from 2008 through 2018. The main outcome measure was clinical relapse rates after ATA withdrawal. Results One hundred seventy patients received scheduled ATA treatment; 78 patients with CD and 56 patients with UC underwent endoscopic reassessment. We found that MH was achieved by 32 patients with CD (41%) and 30 patients with UC (53.6%); 26 patients with CD (33.3%) and 22 patients with UC (39.3%) achieved HH. The ATA treatment was suspended in 45 patients, 24 affected by CD and 21 by UC, who all achieved concurrently complete MH (Simplified Endoscopic Score for CD, 0; Mayo score, 0, respectively) and HH. All the patients who suspended ATA shifted to an immunomodulatory agent or mesalazine. In contrast, 17 patients, 8 with CD and 9 with UC, continued ATA because of growth needs, the persistence of slight endoscopic lesions, and/or microscopic inflammation. Thirteen out of 24 patients with CD who suspended ATA experienced disease relapse after a median follow-up time of 29 months, whereas no recurrence was observed among the 9 patients with CD who continued treatment (P = 0.05). Among the patients with UC, there were no significant differences in relapse-free survival among those who discontinued ATA and those who did not suspend treatment (P = 0.718). Conclusions Despite the application of rigid selection criteria, ATA cessation remains inadvisable in CD. In contrast, in UC, the concurrent achievement of MH and HH may represent promising selection criteria to identify patients in whom treatment withdrawal is feasible.

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