Department of Dermatology, Centro Hospitalar Universitário do Porto, Porto, Portugal.
Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Am J Clin Dermatol. 2022 Nov;23(6):813-822. doi: 10.1007/s40257-022-00720-0. Epub 2022 Aug 12.
Psoriasis is an immune-mediated disease, with the interleukin (IL)-23/IL-17 axis currently considered its main pathogenic pathway. Tyrosine kinase 2 (TYK2) is responsible for mediating immune signalling of IL-12, IL-23 and type I interferons, without interfering with other critical systemic functions as other JAK proteins do. This article aims to review the current knowledge on deucravacitinib, a new oral drug that selectively inhibits TYK2, granting it a low risk of off-target effects. After good efficacy and safety results in a phase II, placebo-controlled trial, two phase III, 52-week trials evaluated deucravacitinib 6 mg against placebo and apremilast-an active comparator. POETYK PSO-1 and PSO-2 involved 1688 patients with moderate-to-severe psoriasis. After 16 weeks, in both studies, over 50% of patients treated with deucravacitinib reached PASI75, which was significantly superior to placebo and apremilast. In POETYK PSO-1, these results improved until week 24 and were maintained through week 52, with over 65% of patients achieving PASI75 at this point. A reduction in signs and symptoms was also reported by patients, with greater impact on itch. Deucravacitinib was well tolerated and safe. There were no reports of serious infections, thromboembolic events, or laboratory abnormalities, which are a concern among other JAK inhibitors. Persistent efficacy and consistent safety profiles were reported for up to 2 years. Despite advances in the treatment of psoriasis, namely among biologic agents, an oral, effective and safe new drug can bring several advantages to prescribers and patients. Further investigation is required to understand where to place deucravacitinib among current psoriasis treatment options.
银屑病是一种免疫介导的疾病,目前认为白细胞介素(IL)-23/IL-17 轴是其主要的发病途径。酪氨酸激酶 2(TYK2)负责介导 IL-12、IL-23 和 I 型干扰素的免疫信号,而不会像其他 JAK 蛋白那样干扰其他关键的全身功能。本文旨在综述新型口服药物地达司他单抗的现有知识,该药物选择性抑制 TYK2,因此具有较低的脱靶效应风险。在一项 II 期、安慰剂对照试验中取得良好的疗效和安全性结果后,两项为期 52 周的 III 期试验评估了地达司他单抗 6mg 与安慰剂和阿普司特的疗效。POETYK PSO-1 和 PSO-2 试验共纳入 1688 例中重度银屑病患者。在这两项研究中,治疗 16 周后,超过 50%接受地达司他单抗治疗的患者达到 PASI75,显著优于安慰剂和阿普司特。在 POETYK PSO-1 中,这些结果在第 24 周时进一步改善,并在第 52 周时得到维持,此时超过 65%的患者达到 PASI75。患者还报告了症状和体征的改善,瘙痒的改善更为显著。地达司他单抗耐受性良好且安全。无严重感染、血栓栓塞事件或实验室异常的报告,这是其他 JAK 抑制剂的关注重点。在长达 2 年的时间里,报告了持续的疗效和一致的安全性。尽管在银屑病治疗方面取得了进展,特别是在生物制剂方面,但一种口服、有效且安全的新药可为医生和患者带来诸多优势。需要进一步研究以了解地达司他单抗在当前银屑病治疗方案中的定位。