Apremilast Pharmacogenomics in Russian Patients with Moderate-to-Severe and Severe Psoriasis

Abstract

One of the target drugs for plaque psoriasis treatment is apremilast, which is a selective phosphodiesterase 4 (PDE4) inhibitor. In this study, 34 moderate-to-severe and severe plaque psoriasis patients from Russia were treated with apremilast for 26 weeks. This allowed us to observe the effectiveness of splitting patient cohorts based on clinical outcomes, which were assessed using the Psoriasis Area Severity Index (PASI). In total, 14 patients (41%) indicated having an advanced outcome with delta PASI 75 after treatment; 20 patients indicated having moderate or no effects. Genome variability was investigated using the Illumina Infinium Global Screening Array. Genome-wide analysis revealed apremilast therapy clinical outcome associations at three compact genome regions with undefined functions situated on chromosomes 2, 4, and 5, as well as on a single single-nucleotide polymorphism (SNP) on chromosome 23. Pre-selected SNP sets were associated with psoriasis vulgaris analysis, which was used to identify four SNP-associated targeted therapy efficiencies: IL1β (rs1143633), IL4 (IL13) (rs20541), IL23R (rs2201841), and TNFα (rs1800629) genes. Moreover, we showed that the use of the global polygenic risk score allowed for the prediction of onset psoriasis in Russians. Therefore, these results can serve as a starting point for creating a predictive model of apremilast therapy response in the targeted therapy of patients with psoriasis vulgaris.