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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doaj-81eb385d7e2649958830718e9afb63b92020-11-25T02:47:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01135e019679310.1371/journal.pone.0196793Validation study of genetic biomarkers of response to TNF inhibitors in rheumatoid arthritis.Rosario Lopez-RodriguezEva Perez-PampinAna MarquezFrancisco J BlancoBeatriz JovenPatricia CarreiraMiguel Angel FerrerRafael CalizLara ValorJavier NarvaezJuan D CañeteMaria Del Carmen OrdoñezSara Manrique-ArijaYiannis VasilopoulosAlejandro BalsaDora Pascual-SalcedoManuel J Moreno-RamosJuan Jose Alegre-SanchoFederico Navarro-SarabiaVirginia MoreiraRosa Garcia-PortalesEnrique RayaCesar Magro-ChecaJavier MartinJuan J Gomez-ReinoAntonio GonzalezGenetic 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.http://europepmc.org/articles/PMC5937760?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rosario Lopez-Rodriguez Eva Perez-Pampin Ana Marquez Francisco J Blanco Beatriz Joven Patricia Carreira Miguel Angel Ferrer Rafael Caliz Lara Valor Javier Narvaez Juan D Cañete Maria Del Carmen Ordoñez Sara Manrique-Arija Yiannis Vasilopoulos Alejandro Balsa Dora Pascual-Salcedo Manuel J Moreno-Ramos Juan Jose Alegre-Sancho Federico Navarro-Sarabia Virginia Moreira Rosa Garcia-Portales Enrique Raya Cesar Magro-Checa Javier Martin Juan J Gomez-Reino Antonio Gonzalez |
spellingShingle |
Rosario Lopez-Rodriguez Eva Perez-Pampin Ana Marquez Francisco J Blanco Beatriz Joven Patricia Carreira Miguel Angel Ferrer Rafael Caliz Lara Valor Javier Narvaez Juan D Cañete Maria Del Carmen Ordoñez Sara Manrique-Arija Yiannis Vasilopoulos Alejandro Balsa Dora Pascual-Salcedo Manuel J Moreno-Ramos Juan Jose Alegre-Sancho Federico Navarro-Sarabia Virginia Moreira Rosa Garcia-Portales Enrique Raya Cesar Magro-Checa Javier Martin Juan J Gomez-Reino Antonio Gonzalez Validation study of genetic biomarkers of response to TNF inhibitors in rheumatoid arthritis. PLoS ONE |
author_facet |
Rosario Lopez-Rodriguez Eva Perez-Pampin Ana Marquez Francisco J Blanco Beatriz Joven Patricia Carreira Miguel Angel Ferrer Rafael Caliz Lara Valor Javier Narvaez Juan D Cañete Maria Del Carmen Ordoñez Sara Manrique-Arija Yiannis Vasilopoulos Alejandro Balsa Dora Pascual-Salcedo Manuel J Moreno-Ramos Juan Jose Alegre-Sancho Federico Navarro-Sarabia Virginia Moreira Rosa Garcia-Portales Enrique Raya Cesar Magro-Checa Javier Martin Juan J Gomez-Reino Antonio Gonzalez |
author_sort |
Rosario Lopez-Rodriguez |
title |
Validation study of genetic biomarkers of response to TNF inhibitors in rheumatoid arthritis. |
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. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2018-01-01 |
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. |
url |
http://europepmc.org/articles/PMC5937760?pdf=render |
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