Genetic Predictors of Long-term Response to Antitumor Necrosis Factor Agents in Pediatric Inflammatory Bowel Disease

Objectives: Inflammatory bowel disease (IBD) is more complex in children and they will have to live with the disease for much longer. For this reason, it is necessarytooptimizetreatment. Thepolymorphismsassociatedwiththeresponse to anti-tumor necrosis factor (TNF) drugs in adults with IBD have not b...

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Detalles Bibliográficos
Autores: Salvador-Martin, S, Bossacoma, F, Pujol-Muncunill, G, Navas-Lopez, VM, Gallego-Fernandez, C, Viada, J, Munoz-Codoceo, R, Magallares, L, Martinez-Ojinaga, E, Moreno-Alvarez, A, Solar-Boga, A, Segarra, O, Clemente, S, Rodriguez-Martinez, A, Alvarez-Vayo, C, Loverdos, I, Merino-Bohorquez, V, Balboa-Vega, MJ, Blanca-Garcia, JA, Fobelo, MJ, Millan-Jimenez, A, Garcia-Romero, R, Sanchez, C, Tolin, M, de Caldas, RG, Eizaguirre, FJ, Sanchez-Hernandez, JG, Torres-Peral, R, Aznal, E, Garcia-Gonzalez, X, Sanjurjo-Saez, M, Lopez-Fernandez, LA
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Institut d'Investigació i Innovació Parc Taulí (I3PT)
Repositorio:r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
OAI Identifier:oai:i3pt.fundanetsuite.com:p2470
Acceso en línea:https://i3pt.portalinvestigacion.com/publicaciones/2470
Access Level:acceso abierto
Palabra clave:adalimumab
children
infliximab
pharmacogenetics
single-nucleotide polymorphisms
Descripción
Sumario:Objectives: Inflammatory bowel disease (IBD) is more complex in children and they will have to live with the disease for much longer. For this reason, it is necessarytooptimizetreatment. Thepolymorphismsassociatedwiththeresponse to anti-tumor necrosis factor (TNF) drugs in adults with IBD have not been analyzed in children. The aim of the study was to identify genetic variants associated with the long-term response to anti-TNF drugs in children with IBD. Methods: An observational, longitudinal, ambispective cohort's study was conducted. Werecruited 209 anti-TNF-treated children diagnosed with IBDand genotyped 21 polymorphisms previously studied in adults with Crohn disease (CD) using real-time PCR. The association between single-nucleotide polymorphisms (SNPs) and time-to-failure was analyzed using the log-rank test. Results: After multivariate analysis, 3 SNPs in IL10, IL17A and IL6 were significantly associated with response to anti-TNF treatment among patients diagnosed with CD (rs1800872-HR, 4.749 (95% confidence interval [CI] 1.156-19.517), P value< 0.05; rs2275913-HR, 0.320 [95% CI 0.1110.920], P value < 0.05; and rs10499563-HR, 0.210 [95% CI 0.0470.947], P value 0.05, respectively). None of these SNPs were associated with response to infliximab in adults diagnosed with CD. Among patients diagnosed with ulcerative colitis (UC), 1 SNP in LY96 was significantly associated with response to anti-TNF treatment (rs-11465996-HR, 10.220 [95% CI 1.849-56.504] P value < 0.05). Conclusions: Genotyping of these DNA variants before starting treatment may help to identify children who are long-term responders to anti-TNF drugs, and thus tailor treatment of pediatric IBD.

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