Sakkas Lazaros I, Zafiriou Efterpi, Bogdanos Dimitrios P
Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.
Department of Dermatology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.
Front Pharmacol. 2019 Aug 6;10:872. doi: 10.3389/fphar.2019.00872. eCollection 2019.
Psoriasis, an inflammatory skin disease, and psoriatic arthritis (PsA), an inflammatory arthritis, share clinical, genetic, and pathogenic factors and may be summed as one disease, the psoriatic disease. Interleukin (IL)-17 plays a major role in the development of both psoriasis and PsA. IL-23 is important in the proliferation and maintenance of IL-17, and therefore, cytokines of the IL-23/IL-17 axis attracted much interest as therapeutic targets in psoriasis and PsA. Therapeutic agents targeting the IL-23/IL-17 axis have been proven to be very effective in psoriasis and PsA, some are already in the therapeutic armamentarium and others are in the development. Some agents, target IL-23 and others IL-17 and include anti-IL-12/IL-23 p40 (ustekinumab, briankizumab), anti-IL-23p19 (guselkumab, tildrakizumab, risankizumab, brazikumab, mirikizumab), anti-IL-17A (secukinumab, ixekizumab), dual anti-IL-17A and anti-IL-17F (bimekizumab), or anti-IL-17 receptor (brodalumab) monoclonal antibodies. Janus tyrosine kinase(JAK) inhibitors also directly affect IL-23 and, thus, IL-17. After the first-generation pan-JAK inhibitors have been shown efficacy (tofacitinib, baricitinib), new-generation selective JAK inhibitors (filgotinib, upadacitinib) are under investigation in psoriasis and PsA.
银屑病是一种炎症性皮肤病，而银屑病关节炎（PsA）是一种炎症性关节炎，二者具有共同的临床、遗传和致病因素，可归纳为一种疾病，即银屑病性疾病。白细胞介素（IL）-17在银屑病和PsA的发病过程中起主要作用。IL-23对IL-17的增殖和维持很重要，因此，IL-23/IL-17轴的细胞因子作为银屑病和PsA的治疗靶点备受关注。已证实靶向IL-23/IL-17轴的治疗药物在银屑病和PsA中非常有效，有些已用于治疗，其他的仍在研发中。一些药物靶向IL-23，另一些靶向IL-17，包括抗IL-12/IL-23 p40（优特克单抗、布罗利尤单抗）、抗IL-23p19（古塞库单抗、替拉珠单抗、司库奇尤单抗、巴瑞昔库单抗、mirikizumab）、抗IL-17A（司库奇尤单抗、依奇珠单抗）、抗IL-17A和抗IL-17F双抗（比美吉珠单抗）或抗IL-17受体（布罗达单抗）单克隆抗体。Janus酪氨酸激酶（JAK）抑制剂也直接影响IL-23，进而影响IL-17。在第一代泛JAK抑制剂显示出疗效（托法替布、巴瑞替尼）后，新一代选择性JAK抑制剂（非戈替尼、乌帕替尼）正在银屑病和PsA中进行研究。
