Pharmacogenetic biomarkers for secukinumab response in psoriasis patients in real-life clinical practice

BackgroundPrediction of the response to a biological treatment in psoriasis patients would allow efficient treatment allocation.ObjectiveTo identify polymorphisms associated with secukinumab response in psoriasis patients in a daily practice setting.MethodsWe 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.ResultsA 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.ConclusionWe 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.