Department of Dermatology, Corporal Michael J. Crescenz VAMC, Philadelphia, PA, USA.
Perelman School of Medicine, Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USA.
Expert Opin Emerg Drugs. 2023 Dec;28(4):257-273. doi: 10.1080/14728214.2023.2273536. Epub 2023 Dec 26.
Cutaneous lupus erythematosus (CLE) is an autoimmune disease that is clinically heterogenous and may occur with or without the presence of systemic lupus erythematosus (SLE). While existing on a spectrum, CLE and SLE present differences in their underlying pathogenesis and therapeutic responses. No new therapies have been approved in recent decades by the U.S. Food and Drug Administration for CLE, although frequently refractory to conventional therapies. There is an unmet need to develop effective drugs for CLE as it significantly impacts patients' quality of life and may leave irreversible disfiguring damage.
This review provides an update on the latest phase 2 and 3 clinical trials performed in CLE or SLE using skin-specific outcome measures. Emergent therapies are presented alongside their mechanism of action as recent translational studies have permitted identification of critical targets among immune cells and/or pathways involved in CLE.
While the recent literature has few trials for CLE, drugs targeting type I interferon, its downstream signaling and plasmacytoid dendritic cells have shown promising results. Further research is required to develop long-awaited effective therapies, and this review highlights the importance of implementing trials dedicated to CLE to fill the current gap in CLE therapeutics.
皮肤红斑狼疮(CLE)是一种自身免疫性疾病,临床表现具有异质性,可能伴有或不伴有系统性红斑狼疮(SLE)。尽管存在于同一谱系中,但 CLE 和 SLE 在其潜在发病机制和治疗反应方面存在差异。近几十年来,美国食品和药物管理局(FDA)尚未批准任何新的治疗 CLE 的药物,尽管它们通常对传统疗法有抗药性。由于 CLE 严重影响患者的生活质量,并可能留下不可逆转的毁容性损害,因此迫切需要开发有效的 CLE 药物。
本文综述了最新的 CLE 或 SLE 皮肤特异性结局指标的 2 期和 3 期临床试验,介绍了新兴疗法及其作用机制,因为最近的转化研究已经确定了 CLE 中涉及的免疫细胞和/或通路的关键靶点。
尽管最近的文献中 CLE 的试验较少,但针对 I 型干扰素、其下游信号转导和浆细胞样树突状细胞的药物已显示出良好的效果。需要进一步研究以开发期待已久的有效疗法,本综述强调了开展专门针对 CLE 的试验的重要性,以填补 CLE 治疗领域的当前空白。