Dermatology Centre, Northern Care Alliance NHS Foundation Trust, 2 NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
Centre for Genetics and Genomics versus Arthritis, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.
Expert Rev Clin Pharmacol. 2023 Jan-Jun;16(6):549-558. doi: 10.1080/17512433.2023.2219054. Epub 2023 Jun 7.
Psoriasis is a chronic inflammatory skin disease affecting approximately 60 million people worldwide. Genome-wide association studies (GWAS) have allowed identification of novel therapeutic targets in psoriasis including tyrosine kinase 2 (TYK2) where an exonic variant within the gene increases the risk of developing psoriasis.
This review discusses the role of TYK2 in psoriasis pathogenesis, how that relates to genetic variants and recently published ground-breaking clinical trials of novel TYK2 inhibitors. Keyword searches of PubMed were made until January 2023, using the terms: 'TYK2 inhibitor,' 'TYK2 inhibitor AND psoriasis' and 'TYK2 AND GWAS.' Articles and references have been thoroughly reviewed by the authors.
The TYK2 inhibitor deucravacitinib shows promise as an effective oral agent for treating psoriasis. Longer term data are needed to know if thrombotic risk/cancer risk is distinct from other Janus kinase (JAK) inhibitors. Psoriasis is a complex genetic disease for which risk is influenced by genes and environmental factors. GWAS studies have identified several regions of DNA associated with increased risk of disease. We believe that pathway analysis by genetic and genomic means will be key to optimizing TYK2 therapy for the right person at the right time.
银屑病是一种影响全球约 6000 万人的慢性炎症性皮肤病。全基因组关联研究(GWAS)已经确定了银屑病的新治疗靶点,包括酪氨酸激酶 2(TYK2),该基因内的一个外显子变异增加了患银屑病的风险。
本文讨论了 TYK2 在银屑病发病机制中的作用,以及它与遗传变异的关系,以及最近发表的关于新型 TYK2 抑制剂的突破性临床试验。截至 2023 年 1 月,作者使用术语“TYK2 抑制剂”、“TYK2 抑制剂和银屑病”以及“TYK2 和 GWAS”在 PubMed 上进行了关键词搜索。作者对文章和参考文献进行了全面审查。
TYK2 抑制剂德瓦鲁单抗有望成为治疗银屑病的有效口服药物。需要更长时间的数据来了解血栓形成风险/癌症风险是否与其他 Janus 激酶(JAK)抑制剂不同。银屑病是一种复杂的遗传疾病,其风险受基因和环境因素的影响。GWAS 研究已经确定了与疾病风险增加相关的几个 DNA 区域。我们相信,通过遗传和基因组手段进行通路分析将是为合适的人在合适的时间优化 TYK2 治疗的关键。