Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, The University of Manchester, Manchester, M6 8HD, UK.
Am J Clin Dermatol. 2016 Jun;17(3):191-200. doi: 10.1007/s40257-016-0179-3.
Several classes of new oral therapy are in use or in development for the treatment of psoriasis. Despite the high efficacy of biologics, new oral therapies remain important as patients generally prefer this mode of administration and they offer an alternative risk-benefit profile. In this review, we discuss the novel modes of action of these drugs, including modulation of cellular pathways involving diverse targets such as Janus kinase, phosphodiesterase 4, sphingosine 1-phosphate, A3 adenosine receptor and rho-associated kinase 2. We review the available evidence around licensed drugs (apremilast) and drugs that are advanced (tofacitinib) or early (ponesimod, baricitinib, peficitinib, INCB039110, CF101, KD025) in the development pipeline. The key limitations of these oral therapies are their modest efficacy profile (apremilast, ponesimod) and the limitations of their safety profile (tofacitinib, ponesimod), while the evidence for the early pipeline drugs are at phase II level only. Potential niches of current unmet needs include apremilast for patients with concomitant psoriatic arthritis, as combination treatments with biologic therapies, and/or for patients in whom multiple biologic therapies have failed due to immunogenicity and secondary inefficacy. The present knowledge gap regarding these novel drugs includes the need for longer clinical trials or observational studies to evaluate safety, and randomised phase III trials for the early pipeline drugs. We conclude that further research and data are necessary to conclusively establish the role of these agents in the current psoriasis treatment paradigm.
有几类新型口服疗法已被用于或正在开发中，以治疗银屑病。尽管生物制剂的疗效很高，但新的口服疗法仍然很重要，因为患者通常更喜欢这种给药方式，而且它们提供了一种替代的风险效益比。在这篇综述中，我们讨论了这些药物的新型作用机制，包括调节涉及多种靶点的细胞通路，如 Janus 激酶、磷酸二酯酶 4、鞘氨醇 1-磷酸、A3 腺苷受体和 rho 相关激酶 2。我们回顾了已获许可的药物（阿普司特）和开发中处于后期（托法替尼）或早期（泊马度胺、巴瑞替尼、培非司特、INCB039110、CF101、KD025）的药物的现有证据。这些口服疗法的主要局限性在于其疗效适度（阿普司特、泊马度胺）和安全性有限（托法替尼、泊马度胺），而早期药物的证据仅处于 II 期水平。目前未满足需求的潜在领域包括阿普司特适用于同时患有银屑病关节炎的患者，作为与生物疗法的联合治疗，以及/或对于因免疫原性和继发性疗效不佳而多次生物疗法失败的患者。这些新型药物目前存在的知识空白包括需要进行更长时间的临床试验或观察性研究来评估安全性，以及早期药物的随机 III 期试验。我们得出结论，需要进一步研究和数据来明确这些药物在当前银屑病治疗模式中的作用。
