Pharmacogenetic variants of infliximab response in young patients with inflammatory bowel disease

Abstract Infliximab is commonly used in inflammatory bowel disease (IBD), however, differences in clinical response among patients are common. Several studies have considered the possibility that these differences are caused by genetic variability even if no unique marker has been yet identified in...

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Autores principales:	Debora Curci, Marianna Lucafò, Adriana Cifù, Martina Fabris, Matteo Bramuzzo, Stefano Martelossi, Raffaella Franca, Giuliana Decorti, Gabriele Stocco
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	Therapeutics. Pharmacology RM1-950 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/e408575cf9204c19966ff15cc6a33963
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spelling	oai:doaj.org-article:e408575cf9204c19966ff15cc6a339632021-11-19T17:51:34ZPharmacogenetic variants of infliximab response in young patients with inflammatory bowel disease1752-80621752-805410.1111/cts.13075https://doaj.org/article/e408575cf9204c19966ff15cc6a339632021-11-01T00:00:00Zhttps://doi.org/10.1111/cts.13075https://doaj.org/toc/1752-8054https://doaj.org/toc/1752-8062Abstract Infliximab is commonly used in inflammatory bowel disease (IBD), however, differences in clinical response among patients are common. Several studies have considered the possibility that these differences are caused by genetic variability even if no unique marker has been yet identified in pediatric patients. We evaluated the impact of two candidate single‐nucleotide polymorphisms (SNPs) rs396991 in FCGR3A and rs1800629 in TNFα genes on infliximab response in an Italian cohort of 76 pediatric patients with IBD. Results showed that patients with the variant FCGR3A allele had a reduced clinical response at the end of induction (p value = 0.004), at 22 weeks (p value = 0.001), and at 52 weeks of treatment (p value = 0.01). A significant association between the FCGR3A variant and median infliximab levels measured during maintenance therapy was also observed: patients with wild type genotype had higher infliximab levels compared to patient with variant allele. Furthermore, patients with the variant allele had a higher probability to produce antidrug antibodies (ADAs). No association was found among the TNFα SNP, clinical response, and infliximab levels. This study addressed for the first time in pediatric patients with IBD, the association of FCGR3A SNP, infliximab response, and ADA production.Debora CurciMarianna LucafòAdriana CifùMartina FabrisMatteo BramuzzoStefano MartelossiRaffaella FrancaGiuliana DecortiGabriele StoccoWileyarticleTherapeutics. PharmacologyRM1-950Public aspects of medicineRA1-1270ENClinical and Translational Science, Vol 14, Iss 6, Pp 2184-2192 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Therapeutics. Pharmacology RM1-950 Public aspects of medicine RA1-1270
spellingShingle	Therapeutics. Pharmacology RM1-950 Public aspects of medicine RA1-1270 Debora Curci Marianna Lucafò Adriana Cifù Martina Fabris Matteo Bramuzzo Stefano Martelossi Raffaella Franca Giuliana Decorti Gabriele Stocco Pharmacogenetic variants of infliximab response in young patients with inflammatory bowel disease
description	Abstract Infliximab is commonly used in inflammatory bowel disease (IBD), however, differences in clinical response among patients are common. Several studies have considered the possibility that these differences are caused by genetic variability even if no unique marker has been yet identified in pediatric patients. We evaluated the impact of two candidate single‐nucleotide polymorphisms (SNPs) rs396991 in FCGR3A and rs1800629 in TNFα genes on infliximab response in an Italian cohort of 76 pediatric patients with IBD. Results showed that patients with the variant FCGR3A allele had a reduced clinical response at the end of induction (p value = 0.004), at 22 weeks (p value = 0.001), and at 52 weeks of treatment (p value = 0.01). A significant association between the FCGR3A variant and median infliximab levels measured during maintenance therapy was also observed: patients with wild type genotype had higher infliximab levels compared to patient with variant allele. Furthermore, patients with the variant allele had a higher probability to produce antidrug antibodies (ADAs). No association was found among the TNFα SNP, clinical response, and infliximab levels. This study addressed for the first time in pediatric patients with IBD, the association of FCGR3A SNP, infliximab response, and ADA production.
format	article
author	Debora Curci Marianna Lucafò Adriana Cifù Martina Fabris Matteo Bramuzzo Stefano Martelossi Raffaella Franca Giuliana Decorti Gabriele Stocco
author_facet	Debora Curci Marianna Lucafò Adriana Cifù Martina Fabris Matteo Bramuzzo Stefano Martelossi Raffaella Franca Giuliana Decorti Gabriele Stocco
author_sort	Debora Curci
title	Pharmacogenetic variants of infliximab response in young patients with inflammatory bowel disease
title_short	Pharmacogenetic variants of infliximab response in young patients with inflammatory bowel disease
title_full	Pharmacogenetic variants of infliximab response in young patients with inflammatory bowel disease
title_fullStr	Pharmacogenetic variants of infliximab response in young patients with inflammatory bowel disease
title_full_unstemmed	Pharmacogenetic variants of infliximab response in young patients with inflammatory bowel disease
title_sort	pharmacogenetic variants of infliximab response in young patients with inflammatory bowel disease
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/e408575cf9204c19966ff15cc6a33963
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Pharmacogenetic variants of infliximab response in young patients with inflammatory bowel disease

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