Department of Dermatology, Centro Hospitalar do Porto, Rua D. Manuel II, S/N, ex-CICAP, 4099-001, Porto, Portugal.
Instituto de Ciências Biomédicas Abel Salazar, Univertisty of Porto, Porto, Portugal.
Clin Drug Investig. 2018 Feb;38(2):101-112. doi: 10.1007/s40261-017-0596-y.
Psoriasis is a common, chronic, immune-mediated disease associated with several comorbidities. Biologic therapy revolutionized the treatment of moderate-to-severe psoriasis, improving physical and emotional burden of the disease. Still, there are unmet needs in the treatment of psoriasis regarding long-term efficacy, tolerability, safety, route of administration, and cost. The increased knowledge of the pathogenesis of the intracellular metabolic pathways allowed the development of new compounds that inhibit certain intracellular proteins involved in the immune response. Tofacitinib is an oral small molecule that inhibits JAK/STAT pathway, which is then unable to upregulate the pro-inflammatory genes implicated in psoriasis. Data from phase II and III trials reveal that tofacitinib is a well-tolerated treatment for moderate-to-severe chronic plaque psoriasis with sustained efficacy for up to 2 years. With a convenient oral administration in the absence of organ toxicity associated with conventional oral treatments, tofacitinib may represent an important therapeutic to be included in the treatment algorithms of psoriasis.
银屑病是一种常见的、慢性的、免疫介导的疾病,与多种合并症相关。生物疗法彻底改变了中重度银屑病的治疗方式,改善了疾病的身体和心理负担。然而,在银屑病的治疗方面,仍存在一些未满足的需求,如长期疗效、耐受性、安全性、给药途径和成本。对细胞内代谢途径发病机制的深入了解,使得能够开发出抑制参与免疫反应的某些细胞内蛋白质的新型化合物。托法替尼是一种口服小分子药物,可抑制 JAK/STAT 通路,从而无法上调与银屑病相关的促炎基因。来自 II 期和 III 期试验的数据表明,托法替尼是一种耐受性良好的中重度慢性斑块型银屑病治疗药物,疗效可持续长达 2 年。托法替尼具有方便的口服给药途径,不存在与传统口服治疗相关的器官毒性,因此可能是治疗银屑病的重要治疗方法之一。