Dermatology Department, Hospital Universitario de la Princesa, 28006 Madrid, Spain.
Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria La Princesa (IP), 28006 Madrid, Spain.
Medicina (Kaunas). 2020 Dec 20;56(12):719. doi: 10.3390/medicina56120719.
Psoriasis is a chronic immune-mediated skin disease caused by several complex factors, both environmental and genetic, many of which are still not fully understood. Nowadays, several groups of biological drugs are being used for psoriasis treatment. Although these therapies are very effective, they show significant variability in efficacy among individuals. Therefore, there is a need for biomarkers to predict treatment outcomes in order to guide personalized therapeutic decisions. Pharmacogenetics is the study of variations in DNA sequences related to drug response. In this article, we review pharmacogenetics studies on the treatment of moderate-to-severe psoriasis focusing on anti-interleukin (IL) 12/23 (ustekinumab) and anti-IL17 drugs (secukinumab and ixekizumab), as well as recent studies concerning anti-TNF drugs. Several polymorphisms have been studied over the years in reference to anti-TNF drugs; some of the most recent studies included the performance of a genome-wide association study (GWAS) and pharmacogenetics studies focused on the optimization of a treatment regimen. Various polymorphisms in different genes have been related to ustekinumab response; among them, the most commonly studied is the HLA-C*06:02 allele. Although not confirmed in some studies, most studies have shown that patients carrying this allele present a significantly higher response rate to ustekinumab. Some polymorphisms have been studied in patients treated with anti-IL17 drugs, mostly related to secukinumab; however, up to now, no association has been found between any of these polymorphisms and response. Nevertheless, further studies involving larger cohorts are needed in order to confirm these results before the implementation of this biomarker in clinical practice.
银屑病是一种由多种复杂因素引起的慢性免疫介导性皮肤病，包括环境和遗传因素，其中许多因素尚未完全了解。目前，有几类生物药物被用于治疗银屑病。尽管这些疗法非常有效，但它们在个体中的疗效存在显著差异。因此，需要生物标志物来预测治疗结果，以指导个体化的治疗决策。药物遗传学是研究与药物反应相关的 DNA 序列变异的学科。本文综述了针对中重度银屑病治疗的药物遗传学研究，重点关注抗白细胞介素（IL）12/23（乌司奴单抗）和抗 IL17 药物（司库奇尤单抗和依奇珠单抗），以及最近关于抗 TNF 药物的研究。多年来，已经研究了几种与抗 TNF 药物相关的多态性；最近的一些研究包括全基因组关联研究（GWAS）和针对治疗方案优化的药物遗传学研究。不同基因中的多种多态性与乌司奴单抗的反应有关；其中研究最多的是 HLA-C*06:02 等位基因。尽管在一些研究中未得到证实，但大多数研究表明，携带该等位基因的患者对乌司奴单抗的反应率显著更高。一些与抗 IL17 药物治疗相关的患者也研究了多态性，主要与司库奇尤单抗有关；然而，到目前为止，尚未发现这些多态性与任何一种与反应相关。然而，需要进一步涉及更大队列的研究来确认这些结果，然后才能在临床实践中实施该生物标志物。
