Validation Study Of Genetic Biomarkers Of Response To Tnf Inhibitors In Rheumatoid Arthritis

Genetic biomarkers are sought to personalize treatment of patients with rheumatoid arthritis (RA), given their variable response to TNF inhibitors (TNFi). However, no genetic biomaker is yet sufficiently validated. Here, we report a validation study of 18 previously reported genetic biomarkers, incl...

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Autores: López-Rodríguez, Rosario, Perez-Pampin, Eva, Márquez, Ana, Blanco, Francisco J., Joven, Beatriz, Carreira, Patricia, Ferrer, Miguel Angel, Caliz, Rafael, Valor, Lara, Narváez García, Francisco Javier, Canete, Juan D., Ordóñez, María del Carmen, Manrique Arija, Sara, Vasilopoulos, Yiannis, Balsa, Alejandro, Pascual-Salcedo, Dora, Moreno-Ramos, Manuel J., Alegre-Sancho, Juan José, Navarro Sarabia, Federico, Moreira, Virginia, Garcia Portales, Rosa, Raya, Enrique, Magro Checa, Cesar, Martín, Javier, Gomez Reino, Juan J., Gonzalez, Antonio
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/123909
Acceso en línea:https://hdl.handle.net/2445/123909
Access Level:acceso abierto
Palabra clave:Artritis reumatoide
Marcadors bioquímics
Rheumatoid arthritis
Biochemical markers
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spelling Validation Study Of Genetic Biomarkers Of Response To Tnf Inhibitors In Rheumatoid ArthritisLópez-Rodríguez, RosarioPerez-Pampin, EvaMárquez, AnaBlanco, Francisco J.Joven, BeatrizCarreira, PatriciaFerrer, Miguel AngelCaliz, RafaelValor, LaraNarváez García, Francisco JavierCanete, Juan D.Ordóñez, María del CarmenManrique Arija, SaraVasilopoulos, YiannisBalsa, AlejandroPascual-Salcedo, DoraMoreno-Ramos, Manuel J.Alegre-Sancho, Juan JoséNavarro Sarabia, FedericoMoreira, VirginiaGarcia Portales, RosaRaya, EnriqueMagro Checa, CesarMartín, JavierGomez Reino, Juan J.Gonzalez, AntonioArtritis reumatoideMarcadors bioquímicsRheumatoid arthritisBiochemical markersGenetic biomarkers are sought to personalize treatment of patients with rheumatoid arthritis (RA), given their variable response to TNF inhibitors (TNFi). However, no genetic biomaker is yet sufficiently validated. Here, we report a validation study of 18 previously reported genetic biomarkers, including 11 from GWAS of response to TNFi. The validation was attempted in 581 patients with RA that had not been treated with biologic antirheumatic drugs previously. Their response to TNFi was evaluated at 3, 6 and 12 months in two ways: change in the DAS28 measure of disease activity, and according to the EULAR criteria for response to antirheumatic drugs. Association of these parameters with the genotypes, obtained by PCR amplification followed by single-base extension, was tested with regression analysis. These analyses were adjusted for baseline DAS28, sex, and the specific TNFi. However, none of the proposed biomarkers was validated, as none showed association with response to TNFi in our study, even at the time of assessment and with the outcome that showed the most significant result in previous studies. These negative results are notable because this was the first independent validation study for 12 of the biomarkers, and because they indicate that prudence is needed in the interpretation of the proposed biomarkers of response to TNFi even when they are supported by very low p values. The results also emphasize the requirement of independent replication for validation, and the need to search protocols that could increase reproducibility of the biomarkers of response to TNFi.Public Library Science2018201820182018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion13 p.application/pdfhttps://hdl.handle.net/2445/123909Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1371/journal.pone.0196793Plos One, 2018, Vol. 13, Issue 5https://doi.org/10.1371/journal.pone.0196793cc by (c) Lopez-Rodriguez, Rosario et al., 2018http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1239092026-05-29T05:05:01Z
dc.title.none.fl_str_mv Validation Study Of Genetic Biomarkers Of Response To Tnf Inhibitors In Rheumatoid Arthritis
title Validation Study Of Genetic Biomarkers Of Response To Tnf Inhibitors In Rheumatoid Arthritis
spellingShingle Validation Study Of Genetic Biomarkers Of Response To Tnf Inhibitors In Rheumatoid Arthritis
López-Rodríguez, Rosario
Artritis reumatoide
Marcadors bioquímics
Rheumatoid arthritis
Biochemical markers
title_short Validation Study Of Genetic Biomarkers Of Response To Tnf Inhibitors In Rheumatoid Arthritis
title_full Validation Study Of Genetic Biomarkers Of Response To Tnf Inhibitors In Rheumatoid Arthritis
title_fullStr Validation Study Of Genetic Biomarkers Of Response To Tnf Inhibitors In Rheumatoid Arthritis
title_full_unstemmed Validation Study Of Genetic Biomarkers Of Response To Tnf Inhibitors In Rheumatoid Arthritis
title_sort Validation Study Of Genetic Biomarkers Of Response To Tnf Inhibitors In Rheumatoid Arthritis
dc.creator.none.fl_str_mv López-Rodríguez, Rosario
Perez-Pampin, Eva
Márquez, Ana
Blanco, Francisco J.
Joven, Beatriz
Carreira, Patricia
Ferrer, Miguel Angel
Caliz, Rafael
Valor, Lara
Narváez García, Francisco Javier
Canete, Juan D.
Ordóñez, María del Carmen
Manrique Arija, Sara
Vasilopoulos, Yiannis
Balsa, Alejandro
Pascual-Salcedo, Dora
Moreno-Ramos, Manuel J.
Alegre-Sancho, Juan José
Navarro Sarabia, Federico
Moreira, Virginia
Garcia Portales, Rosa
Raya, Enrique
Magro Checa, Cesar
Martín, Javier
Gomez Reino, Juan J.
Gonzalez, Antonio
author López-Rodríguez, Rosario
author_facet López-Rodríguez, Rosario
Perez-Pampin, Eva
Márquez, Ana
Blanco, Francisco J.
Joven, Beatriz
Carreira, Patricia
Ferrer, Miguel Angel
Caliz, Rafael
Valor, Lara
Narváez García, Francisco Javier
Canete, Juan D.
Ordóñez, María del Carmen
Manrique Arija, Sara
Vasilopoulos, Yiannis
Balsa, Alejandro
Pascual-Salcedo, Dora
Moreno-Ramos, Manuel J.
Alegre-Sancho, Juan José
Navarro Sarabia, Federico
Moreira, Virginia
Garcia Portales, Rosa
Raya, Enrique
Magro Checa, Cesar
Martín, Javier
Gomez Reino, Juan J.
Gonzalez, Antonio
author_role author
author2 Perez-Pampin, Eva
Márquez, Ana
Blanco, Francisco J.
Joven, Beatriz
Carreira, Patricia
Ferrer, Miguel Angel
Caliz, Rafael
Valor, Lara
Narváez García, Francisco Javier
Canete, Juan D.
Ordóñez, María del Carmen
Manrique Arija, Sara
Vasilopoulos, Yiannis
Balsa, Alejandro
Pascual-Salcedo, Dora
Moreno-Ramos, Manuel J.
Alegre-Sancho, Juan José
Navarro Sarabia, Federico
Moreira, Virginia
Garcia Portales, Rosa
Raya, Enrique
Magro Checa, Cesar
Martín, Javier
Gomez Reino, Juan J.
Gonzalez, Antonio
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Artritis reumatoide
Marcadors bioquímics
Rheumatoid arthritis
Biochemical markers
topic Artritis reumatoide
Marcadors bioquímics
Rheumatoid arthritis
Biochemical markers
description Genetic biomarkers are sought to personalize treatment of patients with rheumatoid arthritis (RA), given their variable response to TNF inhibitors (TNFi). However, no genetic biomaker is yet sufficiently validated. Here, we report a validation study of 18 previously reported genetic biomarkers, including 11 from GWAS of response to TNFi. The validation was attempted in 581 patients with RA that had not been treated with biologic antirheumatic drugs previously. Their response to TNFi was evaluated at 3, 6 and 12 months in two ways: change in the DAS28 measure of disease activity, and according to the EULAR criteria for response to antirheumatic drugs. Association of these parameters with the genotypes, obtained by PCR amplification followed by single-base extension, was tested with regression analysis. These analyses were adjusted for baseline DAS28, sex, and the specific TNFi. However, none of the proposed biomarkers was validated, as none showed association with response to TNFi in our study, even at the time of assessment and with the outcome that showed the most significant result in previous studies. These negative results are notable because this was the first independent validation study for 12 of the biomarkers, and because they indicate that prudence is needed in the interpretation of the proposed biomarkers of response to TNFi even when they are supported by very low p values. The results also emphasize the requirement of independent replication for validation, and the need to search protocols that could increase reproducibility of the biomarkers of response to TNFi.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018
2018
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/123909
url https://hdl.handle.net/2445/123909
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0196793
Plos One, 2018, Vol. 13, Issue 5
https://doi.org/10.1371/journal.pone.0196793
dc.rights.none.fl_str_mv cc by (c) Lopez-Rodriguez, Rosario et al., 2018
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Lopez-Rodriguez, Rosario et al., 2018
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 13 p.
application/pdf
dc.publisher.none.fl_str_mv Public Library Science
publisher.none.fl_str_mv Public Library Science
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,808905

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