Guttman-Yassky Emma, Dhingra Nikhil, Leung Donald Y M
The Rockefeller University, Laboratory for Investigative Dermatology, New York, NY, USA.
Expert Opin Biol Ther. 2013 Apr;13(4):549-61. doi: 10.1517/14712598.2013.758708. Epub 2013 Jan 16.
Atopic dermatitis (AD) is a common inflammatory skin disease regulated by genetic and environmental factors. Both skin barrier defects and aberrant immune responses are believed to drive cutaneous inflammation in AD. Existing therapies rely largely on allergen avoidance, emollients and topical and systemic immune-suppressants, some with significant toxicity and transient efficacy; no specific targeted therapies are in clinical use today. As our specific understanding of the immune and molecular pathways that cause different subsets of AD increases, a variety of experimental agents, particularly biologic agents that target pathogenic molecules bring the promise of safe and effective therapeutics for long-term use.
This paper discusses the molecular pathways characterizing AD, the contributions of barrier and immune abnormalities to its pathogenesis, and development of new treatments that target key molecules in these pathways. In this review, we will discuss a variety of biologic therapies that are in development or in clinical trials for AD, perhaps revolutionizing treatment of this disease.
Biologic agents in moderate to severe AD offer promise for controlling a disease that currently lacks good and safe therapeutics posing a large unmet need. Unfortunately, existing treatments for AD aim to decrease cutaneous inflammation, but are not specific for the pathways driving this disease. An increasing understanding of the immune mechanisms underlying AD brings the promise of narrow targeted therapies as has occurred for psoriasis, another inflammatory skin disease, for which specific biologic agents have been demonstrated to both control the disease and prevent occurrence of new skin lesions. Although no biologic is yet approved for AD, these are exciting times for active therapeutic development in AD that might lead to revolutionary therapeutics for this disease.
特应性皮炎(AD)是一种由遗传和环境因素调控的常见炎症性皮肤病。皮肤屏障缺陷和异常免疫反应均被认为是AD皮肤炎症的驱动因素。现有疗法主要依赖于避免接触过敏原、使用润肤剂以及局部和全身免疫抑制剂,其中一些具有显著毒性且疗效短暂;目前尚无特异性靶向疗法应用于临床。随着我们对导致不同亚型AD的免疫和分子途径的具体认识不断增加,多种实验性药物,尤其是靶向致病分子的生物制剂,为长期安全有效的治疗带来了希望。
本文讨论了AD的分子途径特征、屏障和免疫异常在其发病机制中的作用,以及针对这些途径中关键分子的新治疗方法的开发。在本综述中,我们将讨论多种正在研发或处于AD临床试验阶段的生物疗法,这些疗法可能会彻底改变该疾病的治疗方式。
中重度AD的生物制剂有望控制一种目前缺乏良好且安全治疗方法、存在大量未满足需求的疾病。不幸的是,现有的AD治疗方法旨在减轻皮肤炎症,但并非针对驱动该疾病的途径。对AD潜在免疫机制的认识不断加深,带来了靶向性更强的治疗方法的希望,就像另一种炎症性皮肤病银屑病那样,已经证明特异性生物制剂既能控制疾病,又能预防新皮肤病变的出现。虽然尚无生物制剂获批用于AD,但对于AD积极的治疗研发而言,这是令人兴奋的时期,可能会带来针对该疾病的革命性疗法。