Successful Treatment of Refractory Discoid Lupus Erythematosus with Deucravacitinib

Alice Sohn, Nicole Bouché, G. Lewitt, E. Song
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Abstract

Discoid lupus erythematosus (DLE) is the most common subtype of chronic cutaneous lupus erythematosus (CLE) that may present with or without systemic lupus erythematosus (SLE). Treatment for DLE remains limited, as there are no medications specifically approved to treat DLE. Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, is currently being studied for adults with moderate-to-severe discoid and/or subacute CLE. We report a case of successful treatment of refractory DLE with deucravacitinib. A 65-year-old female with a longstanding history of systemic lupus erythematosus presented with prominent discoid lesions involving the nose, cheeks, and mid upper cutaneous lip. Having tried topical medications, multiple courses of systemic steroids were attempted, but the patient flared shortly after the tapers. Despite the patient experiencing some improvement on mycophenolate mofetil and prednisone, the decision to switch to deucravacitinib was made due to the patient developing multiple infections while on the former regimen. Three months after starting deucravacitinib, the patient returned with their skin completely clear. A better understanding of the molecular pathogenesis of CLE is informing the development of more targeted therapeutic strategies. TYK2 and Janus Kinases (JAKs) both mediate the signaling of cytokines, some of which play a role in the pathogenesis of SLE. Deucravacitinib binds to TYK2 at the regulatory domain, which is unique to its respective kinase unlike conventional Janus Kinase (JAK) inhibitors that bind to the active domain conserved across all JAKs. Deucravacitinib offers more targeted inhibition with a potentially improved safety profile compared to conventional JAK inhibitors.
德拉瓦替尼成功治疗难治性盘状红斑狼疮
盘状红斑狼疮(DLE)是慢性皮肤红斑狼疮(CLE)最常见的亚型,可伴有或不伴有系统性红斑狼疮(SLE)。由于目前还没有专门获准治疗DLE的药物,因此对DLE的治疗仍然有限。Deucravacitinib是一种口服、选择性、异位酪氨酸激酶2(TYK2)抑制剂,目前正在研究用于治疗中重度盘状和/或亚急性CLE成人患者。我们报告了一例用德拉瓦替尼成功治疗难治性盘状红斑狼疮的病例。一位65岁的女性患者长期患有系统性红斑狼疮,鼻部、脸颊和上唇中段出现明显的盘状皮损。在尝试了局部用药后,患者又尝试了多个疗程的全身类固醇治疗,但在停药后不久病情就复发了。尽管患者在使用霉酚酸酯和泼尼松后病情有所好转,但由于患者在使用前一种药物时出现了多次感染,因此决定改用去氯伐他汀。在开始使用去氯伐替尼三个月后,患者的皮肤恢复了完全正常。对CLE分子发病机制的深入了解为开发更具针对性的治疗策略提供了信息。TYK2和Janus激酶(JAKs)都介导细胞因子的信号转导,其中一些细胞因子在系统性红斑狼疮的发病机制中发挥作用。Deucravacitinib与TYK2的调节结构域结合,这是其各自激酶所独有的,而不像传统的Janus激酶(JAK)抑制剂那样与所有JAK的活性结构域结合。与传统的JAK抑制剂相比,Deucravacitinib具有更强的靶向抑制作用,安全性也可能得到改善。
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