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

dc.contributor.authorLopez-Rodriguez, Rosario
dc.contributor.authorPerez-Pampin, Eva
dc.contributor.authorMarquez, Ana
dc.contributor.authorBlanco, Francisco J
dc.contributor.authorJoven, Beatriz
dc.contributor.authorCarreira, Patricia
dc.contributor.authorFerrer, Miguel Angel
dc.contributor.authorCaliz, Rafael
dc.contributor.authorValor, Lara
dc.contributor.authorNarvaez, Javier
dc.contributor.authorCañete, Juan D
dc.contributor.authorOrdoñez, Maria Del Carmen
dc.contributor.authorManrique-Arija, Sara
dc.contributor.authorVasilopoulos, Yiannis
dc.contributor.authorBalsa, Alejandro
dc.contributor.authorPascual-Salcedo, Dora
dc.contributor.authorMoreno-Ramos, Manuel J
dc.contributor.authorAlegre-Sancho, Juan Jose
dc.contributor.authorNavarro-Sarabia, Federico
dc.contributor.authorMoreira, Virginia
dc.contributor.authorGarcia-Portales, Rosa
dc.contributor.authorRaya, Enrique
dc.contributor.authorMagro-Checa, Cesar
dc.contributor.authorMartin, Javier
dc.contributor.authorGomez-Reino, Juan J
dc.contributor.authorGonzalez, Antonio
dc.date.accessioned2023-01-25T10:08:07Z
dc.date.available2023-01-25T10:08:07Z
dc.date.issued2018-05-07
dc.description.abstractGenetic 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.
dc.identifier.doi10.1371/journal.pone.0196793
dc.identifier.essn1932-6203
dc.identifier.pmcPMC5937760
dc.identifier.pmid29734345
dc.identifier.pubmedURLhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937760/pdf
dc.identifier.unpaywallURLhttps://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0196793&type=printable
dc.identifier.urihttp://hdl.handle.net/10668/12431
dc.issue.number5
dc.journal.titlePloS one
dc.journal.titleabbreviationPLoS One
dc.language.isoen
dc.organizationHospital Universitario San Cecilio
dc.organizationHospital Universitario Virgen de las Nieves
dc.organizationHospital Universitario Virgen de la Victoria
dc.organizationHospital Universitario Regional de Málaga
dc.organizationInstituto de Investigación Biomédica de Málaga-IBIMA
dc.organizationHospital Universitario Virgen Macarena
dc.page.numbere0196793
dc.pubmedtypeJournal Article
dc.pubmedtypeResearch Support, Non-U.S. Gov't
dc.rightsAttribution 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.meshAntirheumatic Agents
dc.subject.meshArthritis, Rheumatoid
dc.subject.meshFemale
dc.subject.meshGenetic Markers
dc.subject.meshGenotype
dc.subject.meshHumans
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshReproducibility of Results
dc.subject.meshTumor Necrosis Factor-alpha
dc.titleValidation study of genetic biomarkers of response to TNF inhibitors in rheumatoid arthritis.
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number13
dspace.entity.typePublication
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