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 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.

Evolution of Pediatric Inflammatory Bowel Disease Unclassified (IBD-U): Incorporated With Serological and Gene Expression Profiles

2018 ◽  
Vol 24 (10) ◽  
pp. 2285-2290 ◽  
Author(s):  
Raguraj Chandradevan ◽  
Tatyana Hofmekler ◽  
Kajari Mondal ◽  
Nusrat Harun ◽  
Suresh Venkateswaran ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Pediatric Inflammatory Bowel Disease ◽  
Inflammatory Bowel

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.

scholarly journals Recent advances in understanding and managing pediatric inflammatory bowel disease

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 2097
Author(s):  
Bhaskar Gurram ◽  
Ashish S. Patel
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Tumor Necrosis ◽  
Scientific Discovery ◽  
Controlled Trials ◽  
Alternative Mechanism ◽  
Primary Therapy ◽  
Pediatric Inflammatory Bowel Disease ◽  
Inflammatory Bowel ◽  
Necrosis Factor

The landscape of pediatric inflammatory bowel disease is rapidly evolving. The therapeutic advances seen in the adult arena are rapidly being adopted by pediatric gastroenterologists and evaluated in both controlled trials and real-world experience. Though anti-tumor necrosis factor agents have been the primary therapy over the last decade, recently there has been an expansion of therapeutic targets and alternative mechanism of action drugs with a focus on individualized and personalized therapy. By reviewing epidemiology, pathophysiology, and goals of treatment, we hope to frame the discussion of current and novel therapeutics for the pediatric gastroenterologist. As scientific discovery continues to push the envelope in defining our understanding of pediatric inflammatory bowel disease, the current era of therapeutics gives us hope that a cure may be realized soon.

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