학술논문
Pharmacogenetic biomarkers for secukinumab response in psoriasis patients in real‐life clinical practice.
Document Type
Article
Author
Muñoz‐Aceituno, E.; Butrón‐Bris, B.; Ovejero‐Benito, M. C.; Sahuquillo‐Torralba, A.; Baniandrés Rodríguez, O.; Herrera‐Acosta, E.; Rivera‐Diaz, R.; Ferran, M.; Sánchez‐Carazo, J. L.; Riera‐Monroig, J.; Pujol‐Montcusí, J.; Vidal, D.; de la Cueva, P.; García‐Bustinduy, M.; Ruiz‐Villaverde, R.; Ballescà, F.; Llamas‐Velasco, M.; Navares, M.; Palomar‐Moreno, I.; Sánchez‐García, I.
Source
Subject
*BIOTHERAPY
*SENSITIVITY & specificity (Statistics)
*LOGISTIC regression analysis
*TREATMENT effectiveness
*REGRESSION analysis
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Language
ISSN
0926-9959
Abstract
Background: Prediction of the response to a biological treatment in psoriasis patients would allow efficient treatment allocation. Objective: To identify polymorphisms associated with secukinumab response in psoriasis patients in a daily practice setting. Methods: We studied 180 SNPs in patients with moderate‐to‐severe plaque psoriasis recruited from 15 Spanish hospitals. Treatment effectiveness was evaluated by absolute PASI ≤3 and ≤1 at 6 and 12 months. Individuals were genotyped using a custom Taqman array. Multiple logistic regression models were generated. Sensitivity, specificity and area under the curve (AUC) were analysed. Results: A total of 173 patients were studied at 6 months, (67% achieved absolute PASI ≤ 3 and 65% PASI ≤ 1) and 162 at 12 months (75% achieved absolute PASI ≤ 3 and 64% PASI ≤ 1). Multivariable analysis showed the association of different sets of SNPs with the response to secukinumab. The model of absolute PASI≤3 at 6 months showed best values of sensitivity and specificity. Four SNPs were associated with the capability of achieving absolute PASI ≤ 3 at 6 months. rs1801274 (FCGR2A), rs2431697 (miR‐146a) and rs10484554 (HLCw6) were identified as risk factors for failure to achieve absolute PASI≤3, while rs1051738 (PDE4A) was protective. AUC including these genotypes, weight of patients and history of biological therapy was 0.88 (95% CI 0.83–0.94), with a sensitivity of 48.6% and specificity of 95.7% to discriminate between both phenotypes. Conclusion: We have identified a series of polymorphisms associated with the response to secukinumab capable of predicting the potential response/non‐response to this drug in patients with plaque psoriasis. [ABSTRACT FROM AUTHOR]