Validation study of genetic biomarkers of response to TNF inhibitors in rheumatoid arthritis

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dc.contributor.author López-Rodríguez, Rosario
dc.contributor.author Pérez-Pampin, Eva
dc.contributor.author Márquez, Ana
dc.contributor.author Blanco, Francisco J.
dc.contributor.author Joven, Beatriz
dc.contributor.author Carreira, Patricia
dc.contributor.author Ferrer, Miguel Ángel
dc.contributor.author Caliz, Rafael
dc.contributor.author Valor, Lara
dc.contributor.author Narváez, Javier
dc.contributor.author Cañete, Juan D.
dc.contributor.author Ordóñez, María del Carmen
dc.contributor.author Manrique-Arija, Sara
dc.contributor.author Vasilopoulos, Yiannis
dc.contributor.author Balsa, Alejandro
dc.contributor.author Pascual-Salcedo, Dora
dc.contributor.author Moreno- Ramos, Manuel J.
dc.contributor.author Alegre-Sancho, Juan José
dc.contributor.author Navarro-Sarabia, Federico
dc.contributor.author Moreira, Virginia
dc.contributor.author García-Portales, Rosa
dc.contributor.author Raya, Enrique
dc.contributor.author Magro-Checa, César
dc.contributor.author Martín, Javier
dc.contributor.author Gómez-Reino, Juan J.
dc.contributor.author González, Antonio
dc.contributor.other UAM. Departamento de Medicina es_ES
dc.contributor.other Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ) es_ES
dc.date.accessioned 2018-07-09T16:27:45Z
dc.date.available 2018-07-09T16:27:45Z
dc.date.issued 2018
dc.identifier.citation PLoS ONE 13.5 (2018): e0196793 en_US
dc.identifier.issn 1932-6203 es_ES
dc.identifier.uri http://hdl.handle.net/10486/683943
dc.description.abstract This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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 en_US
dc.description.sponsorship This work was supported by the Instituto de Salud Carlos III (Spain) through grants [PI14/ 01651 and RD16/0012/0014 to AG; and PI12/ 01909 to JJG-R]. These grants are partially financed by the European Regional Development Fund of the EU (FEDER). R. L.-R. was supported by Instituto de Salud Carlos III (Spain) through a Postdoctoral Contract ªSara Borrellº [CD14/00186] en_US
dc.format.extent 13 pag. es_ES
dc.format.mimetype application/pdf en
dc.language.iso eng en
dc.publisher Public Library of Science en_US
dc.relation.ispartof PLos ONE en_US
dc.rights © 2018 Lopez-Rodriguez et al. es_ES
dc.subject.other Genetic biomarkers en_US
dc.subject.other Rheumatoid arthritis en_US
dc.subject.other Response to TNF inhibitors en_US
dc.subject.other Validation en_US
dc.subject.other Study en_US
dc.title Validation study of genetic biomarkers of response to TNF inhibitors in rheumatoid arthritis en_US
dc.type article en
dc.subject.eciencia Medicina es_ES
dc.relation.publisherversion https://doi.org/ 10.1371/journal.pone.0196793 es_ES
dc.identifier.doi 10.1371/journal.pone.0196793 es_ES
dc.identifier.publicationfirstpage e0196793-1 es_ES
dc.identifier.publicationissue 5 es_ES
dc.identifier.publicationlastpage e0196793-13 es_ES
dc.identifier.publicationvolume 13 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion en
dc.rights.cc Reconocimiento es_ES
dc.rights.accessRights openAccess en


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