scholarly journals Gene Signatures of Early Response to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease

2020 ◽  
Vol 21 (9) ◽  
pp. 3364 ◽  
Author(s):  
Sara Salvador-Martín ◽  
Irene Raposo-Gutiérrez ◽  
Víctor Manuel Navas-López ◽  
Carmen Gallego-Fernández ◽  
Ana Moreno-Álvarez ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Expression Profiles ◽  
Statistical Significance ◽  
Early Response ◽  
Response To Treatment ◽  
P Value ◽  
Infliximab Treatment ◽  
Inflammatory Bowel ◽  
Pediatric Ibd

Around a 20–30% of inflammatory bowel disease (IBD) patients are diagnosed before they are 18 years old. Anti-TNF drugs can induce and maintain remission in IBD, however, up to 30% of patients do not respond. The aim of the work was to identify markers that would predict an early response to anti-TNF drugs in pediatric patients with IBD. The study population included 43 patients aged <18 years with IBD who started treatment with infliximab or adalimumab. Patients were classified into primary responders (n = 27) and non-responders to anti-TNF therapy (n = 6). Response to treatment could not be analyzed in 10 patients. Response was defined as a decrease in over 15 points in the disease activity indexes from week 0 to week 10 of infliximab treatment or from week 0 to week 26 of adalimumab treatment. The expression profiles of nine genes in total RNA isolated from the whole-blood of pediatric IBD patients taken before biologic administration and after 2 weeks were analyzed using qPCR and the 2−∆∆Ct method. Before initiation and after 2 weeks of treatment the expression of SMAD7 was decreased in patients who were considered as non-responders (p value < 0.05). Changes in expression were also observed for TLR2 at T0 and T2, although that did not reach the level of statistical significance. In addition, the expression of DEFA5 decreased 1.75-fold during the first 2 weeks of anti-TNF treatment in responders, whereas no changes were observed in non-responders. Expression of the SMAD7 gene is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD. TLR2 and DEFA5 need to be validated in larger studies.

scholarly journals Whole Transcription Profile of Responders to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease

Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 77
Author(s):  
Sara Salvador-Martín ◽  
Bartosz Kaczmarczyk ◽  
Rebeca Álvarez ◽  
Víctor Manuel Navas-López ◽  
Carmen Gallego-Fernández ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Early Response ◽  
P Value ◽  
Pediatric Inflammatory Bowel Disease ◽  
Study Population ◽  
Inflammatory Bowel ◽  
Necrosis Factor

Background: Up to 30% of patients with pediatric inflammatory bowel disease (IBD) do not respond to anti-Tumor Necrosis Factor (anti-TNF) therapy. The aim of this study was to identify pharmacogenomic markers that predict early response to anti-TNF drugs in pediatric patients with IBD. Methods: An observational, longitudinal, prospective cohort study was conducted. The study population comprised 38 patients with IBD aged < 18 years who started treatment with infliximab or adalimumab (29 responders and nine non-responders). Whole gene expression profiles from total RNA isolated from whole blood samples of six responders and six non-responders taken before administration of the biologic and after two weeks of therapy were analyzed using next-generation RNA sequencing. The expression of six selected genes was measured for purposes of validation in all of the 38 patients recruited using qPCR. Results: Genes were differentially expressed in non-responders and responders (32 before initiation of treatment and 44 after two weeks, Log2FC (Fold change) >0.6 or <−0.6 and p value < 0.05). After validation, FCGR1A, FCGR1B, and GBP1 were overexpressed in non-responders two weeks after initiation of anti-TNF treatment (Log2FC 1.05, 1.21, and 1.08, respectively, p value < 0.05). Conclusion: Expression of the FCGR1A, FCGR1B, and GBP1 genes is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD.

scholarly journals The Emerging Role of Noncoding RNAs in Pediatric Inflammatory Bowel Disease

2020 ◽  
Vol 26 (7) ◽  
pp. 985-993 ◽  
Author(s):  
Petr Jabandziev ◽  
Julia Bohosova ◽  
Tereza Pinkasova ◽  
Lumir Kunovsky ◽  
Ondrej Slaby ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Expression Profiles ◽  
Significant Proportion ◽  
Noncoding Rnas ◽  
Inflammatory Disorder ◽  
Altered Expression ◽  
Clinical Biomarkers ◽  
Inflammatory Bowel ◽  
Pediatric Ibd

Abstract Prevalence of inflammatory bowel disease (IBD), a chronic inflammatory disorder of the gut, has been on the rise in recent years—not only in the adult population but also especially in pediatric patients. Despite the absence of curative treatments, current therapeutic options are able to achieve long-term remission in a significant proportion of cases. To this end, however, there is a need for biomarkers enabling accurate diagnosis, prognosis, and prediction of response to therapies to facilitate a more individualized approach to pediatric IBD patients. In recent years, evidence has continued to evolve concerning noncoding RNAs (ncRNAs) and their roles as integral factors in key immune-related cellular pathways. Specific deregulation patterns of ncRNAs have been linked to pathogenesis of various diseases, including pediatric IBD. In this article, we provide an overview of current knowledge on ncRNAs, their altered expression profiles in pediatric IBD patients, and how these are emerging as potentially valuable clinical biomarkers as we enter an era of personalized medicine.

scholarly journals Risk of Prevalent Asthma among Children Affected by Inflammatory Bowel Disease: A Population-Based Birth Cohort Study

2020 ◽  
Vol 17 (12) ◽  
pp. 4255 ◽  
Author(s):  
Claudio Barbiellini Amidei ◽  
Fabiana Zingone ◽  
Loris Zanier ◽  
Cristina Canova
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Early Onset ◽  
Statistical Significance ◽  
Significant Risk ◽  
Population Based ◽  
Birth Cohort Study ◽  
Childhood Onset ◽  
Inflammatory Bowel ◽  
Pediatric Ibd

Literature on the risk of asthma among children with inflammatory bowel disease (IBD) is limited and has reported discording results. To the best of our knowledge, no previous study has evaluated the association between asthma and childhood onset IBD, focusing on pediatric IBD with onset between 10 and 17 years, early-onset IBD (EO-IBD) between 0 and 9 years, and very early-onset IBD (VEO-IBD) between 0 and 5 years, all conditions characterized by different clinical progressions. A nested matched case-control design on a longitudinal cohort of 213,515 newborns was adopted. Conditional binomial regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) of asthma among children with IBD compared with controls. We found 162 children with IBD and 1620 controls. Overall, childhood onset IBD was associated with increased risks of being affected by asthma (OR: 1.49 95% CI 1.05–2.12), although a significant risk was only present among males (OR: 1.60 95% CI 1.02–2.51). Children with Crohn’s disease and ulcerative colitis had similarly increased risks, although they failed to attain statistical significance. Risks of asthma based on age at IBD onset were inversely related to age, with the lowest non-significant risks for pediatric IBD and EO-IBD, while children affected by VEO-IBD had the highest risk of asthma (OR: 2.75 95% CI 1.26–6.02). Our study suggests the presence of a higher prevalence of asthma among both male children with IBD and children with VEO-IBD. It could be advisable to pay greater attention to possible respiratory symptoms among these categories at higher risk.

scholarly journals Oral Vancomycin as an Adjuvant Treatment in IBD

2019 ◽  
Vol 1 (2) ◽  
Author(s):  
Travis D Ayers ◽  
Elaine Leonard-Puppa ◽  
Howard A Kader ◽  
Jaylyn Waddell ◽  
Runa D Watkins ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Adjuvant Treatment ◽  
Bowel Disease ◽  
Activity Index ◽  
P Value ◽  
Physician Global Assessment ◽  
Oral Vancomycin ◽  
Presenting Symptoms ◽  
Inflammatory Bowel ◽  
Pediatric Ibd

Abstract Objective To study the efficacy of oral vancomycin (POV) treatment in pediatric inflammatory bowel disease (IBD). Methods We conducted retrospective and prospective chart reviews, identifying patients using the Division’s Inflammatory Bowel Disease (IBD) registry, ICD-9 and ICD-10 codes for IBD, and recall of patients receiving POV. Patients aged 2–21 years with active IBD at initiation of POV were included unless they had Clostridium difficile infection or primary sclerosing cholangitis (PSC). Pre- and posttreatment analysis included a Physician Global Assessment (PGA), pediatric ulcerative colitis (UC) activity index (PUCAI), and an abbreviated pediatric Crohn’s disease (CD) activity index (PCDAI). The Wilcoxon Signed Ranks test, determined if pre- and post-POV rankings of symptom severity differed. Mann–Whitney U tests assessed improvement in presenting symptoms. Results Nineteen patients met inclusion criteria (12 CD and 7 UC). POV improved the PGA score in 16 of 19 patients (P < 0.001). Mean PGA score pretreatment was 3 ± 0.471; posttreatment mean of 1.58 ± 0.769. Abdominal pain (P < 0.001), diarrhea (P < 0.002), anemia (P < 0.002), and blood in stool (P < 0.001) showed significant improvement. PUCAI and PCDAI scores, pretreatment means of 50 ± 17 and 33 ± 9, respectively, also improved with mean score reduction of 23 in CD and 38 in UC patients after POV initiation (P-value < 0.0001). This improvement was noted for both IBD subtypes. Conclusions POV may be an effective adjuvant treatment for pediatric IBD. Its effectiveness is likely due to a combination of its anti-tumor necrosis factor alpha-α activity and its influence on the gut microbiome. Further controlled studies of POV in IBD are warranted to determine the most efficacious use of POV in pediatric IBD. Aim This study attempts to expand on the current literature to determine efficacy of POV as an adjuvant therapy in treating active IBD in children.

scholarly journals P076 The endocannabinoid system in the intestinal biopsies of children with Inflammatory Bowel Disease

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S178-S180
Author(s):  
M Creoli ◽  
C Strisciuglio ◽  
A Vitale ◽  
F Oglio ◽  
S Paino ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Therapeutic Target ◽  
Cannabinoid Receptors ◽  
Statistical Significance ◽  
Interleukin 1 ◽  
Endocannabinoid System ◽  
Cb2 Receptor ◽  
Inflammatory Bowel ◽  
Pediatric Ibd

Abstract Background The endocannabinoid (EC) system has been recently indicated as a possible therapeutic target in inflammatory bowel disease patients (IBD). G-protein-coupled cannabinoid receptors type 1 and 2 (CB1 and CB2) are the two most important components of the EC system. In our previous study, we demonstrated that a specific CB2 variant contributes to the risk for pediatric IBD, especially UC, and that this variant is associated with a more severe phenotype in both UC and CD. The aim of this study was to directly evaluate on intestinal biopsies of pediatric IBD patients the expression of EC system receptors and of several molecules associated with inflammatory pathway in IBD. Methods In this preliminary study, we analyzed the CB1 and CB2 expression in the intestinal mucosa of paediatric patients affected by Crohn’s disease (CD) or ulcerative colitis (UC), recruited at diagnosis, and of non-IBD healthy controls (HC). Three patients were enrolled for each group. In particular, we analyzed biopsies taken from the ileum and rectum, which are the tract often more inflamed in CD and UC respectively. Moreover, we evaluated Toll-like receptor 4 (TLR 4), interleukin- 6 (IL6), interleukin-1 β (IL1-β), prokineticin receptor 2 (PKR2) expression, which are known as pro-inflammatory elements. The expression of these receptors and pro- inflammatory cytokines was analyzed by western blot and immunofluorescence. Results We found an increased expression of CB2 and TLR4 in UC rectum biopsies compared to CD and HC children. Accordingly, there was also a significant increase of IL-6 expression in UC rectum biopsies compared to CD and HC children (p≤0.05 UC vs HC), as well as, we identified a high expression of IL-6 in CD ileum compared to UC and HC patients. Moreover, in CD ileum, we found an increase in TLR4 compared to UC and HC ileum. We did not find statistical difference for the low number of analyzed samples, but to be a preliminary work we are confident to reach statistical significance increasing the samples enrolled. Conclusion In according with our previous data, our results confirm that the EC system and in particular the receptor CB2 is more expressed in the intestine of IBD patients, especially in the rectum of UC patients, which is the tract with greater inflammatory involvement. We can speculate that CB2 receptor is involved in the pathogenesis of paediatric IBD, but additional functional studies are required to understand how the EC system contributes to disease development in pediatric IBD, and if these cannabinoid receptors might represent a new disease marker and could be used as a potential therapeutic target. Expression of CB2 receptor in rectum biopsies

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 Biosimilar knowledge and viewpoints among Brazilian inflammatory bowel disease patients

2021 ◽  
Vol 14 ◽  
pp. 175628482110132
Author(s):  
Karoline Soares Garcia ◽  
Bianca Pocopetz Facas ◽  
Marta Brenner Machado ◽  
Fábio Vieira Teixeira ◽  
Luisa Avedano ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Tumor Necrosis ◽  
Online Survey ◽  
Lower Cost ◽  
European Federation ◽  
P Value ◽  
Inflammatory Bowel ◽  
Necrosis Factor ◽  
Negative Expectations

Background: In this analysis we aimed to describe Brazilian inflammatory bowel disease (IBD) patients’ knowledge and perceptions regarding biosimilars and compare with viewpoints from non-Brazilian patients. Methods: An online survey consisting of 19 questions was made available by the European Federation of Crohn’s and Ulcerative Colitis Associations between July 2018 and December 2018. Only respondents who had heard of biosimilars were asked to respond to all of the questions. Results: A total of 102 Brazilian IBD patients responded to the survey. The majority (78.4%) of patients had been exposed to anti-tumor-necrosis-factor drugs and 63.4% of them had heard of biosimilars. Brazilian respondents worried significantly more about biosimilars being less effective than the originator (62.5% versus 47.9%, p value 0.03) and molecular differences between biosimilars and originators (53.1% versus 31.8, p value 0.001) as compared with non-Brazilian IBD patients. The majority of Brazilian (75%) and non-Brazilian (64.1%) respondents thought that the lower cost of biosimilars should not come before their safety and efficacy ( p value 0.09). In addition, 79.1% of Brazilian respondents believed that the arrival of biosimilars will have an impact on the management of IBD. Conclusions: Brazilian patients reported higher rates of misconceptions regarding biosimilars than non-Brazilian IBD patients. Although patients still worry about different aspects regarding biosimilars, they also tend to be confident that biosimilars will have an impact on the management of their disease. With the recent approval of many biosimilars in Brazil and the imminent widespread use of these drugs, our data raise awareness for the need of providing patient education to prevent negative expectations toward switching to biosimilars.

Tu1986 TNF-Alpha Activity in Plasma From Patients With Inflammatory Bowel Disease Under Adalimumab and Infliximab Treatment Evaluated in a Cell-Based Assay

2016 ◽  
Vol 150 (4) ◽  
pp. S997-S998
Author(s):  
Pablo M. Linares ◽  
H de la Fuente ◽  
María Chaparro ◽  
Iván Guerra ◽  
Pedro L. Majano ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Alpha Activity ◽  
Tnf Alpha ◽  
Infliximab Treatment ◽  
A Cell ◽  
Inflammatory Bowel
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