RT Journal Article
T1 Validation study of genetic biomarkers of response to TNF inhibitors in rheumatoid arthritis.
A1 Lopez-Rodriguez, Rosario
A1 Perez-Pampin, Eva
A1 Marquez, Ana
A1 Blanco, Francisco J
A1 Joven, Beatriz
A1 Carreira, Patricia
A1 Ferrer, Miguel Angel
A1 Caliz, Rafael
A1 Valor, Lara
A1 Narvaez, Javier
A1 Cañete, Juan D
A1 Ordoñez, Maria Del Carmen
A1 Manrique-Arija, Sara
A1 Vasilopoulos, Yiannis
A1 Balsa, Alejandro
A1 Pascual-Salcedo, Dora
A1 Moreno-Ramos, Manuel J
A1 Alegre-Sancho, Juan Jose
A1 Navarro-Sarabia, Federico
A1 Moreira, Virginia
A1 Garcia-Portales, Rosa
A1 Raya, Enrique
A1 Magro-Checa, Cesar
A1 Martin, Javier
A1 Gomez-Reino, Juan J
A1 Gonzalez, Antonio
K1 Antirheumatic agents
K1 Genetic markers
K1 Tumor necrosis factor-alpha
AB 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.
PB Public Library of Science
YR 2018
FD 2018-04-19
LK http://hdl.handle.net/10668/12431
UL http://hdl.handle.net/10668/12431
LA en
NO Lopez-Rodriguez R, Perez-Pampin E, Marquez A, Blanco FJ, Joven B, Carreira P, et al. Validation study of genetic biomarkers of response to TNF inhibitors in rheumatoid arthritis. PLoS One. 2018 May 7;13(5):e0196793
DS RISalud
RD Apr 20, 2025