Knecht-Gurwin Klaudia, Matusiak Lukasz, Szepietowski Jacek C
University Centre of General Dermatology and Oncodermatology, Wroclaw Medical University, Wroclaw, Poland.
Department of Dermato-Venereology, 4th Military Hospital, Wroclaw, Poland.
Expert Opin Drug Discov. 2025 Apr;20(4):405-417. doi: 10.1080/17460441.2025.2482058. Epub 2025 Mar 19.
Hidradenitis suppurativa (HS) is a chronic skin condition with a significant impact on patient quality of life, highlighting the need for innovative therapeutic approaches. HS is characterized by its chronicity; it presents in the form of painful nodules, abscesses, and sinus tracts or fistulas, typically localized in intertriginous areas, emerging in early adulthood and in predominantly the female population.
In this review, the authors discuss the preclinical discovery and development of secukinumab for HS, highlighting target identification, validation, and compound selection. Methodologies such as high-content screening, chemoinformatics, and animal models that validate the IL-17 pathway's role in HS are explored. The transition from preclinical to clinical development, including pharmacokinetics (PK), pharmacodynamics (PD), and ADME-Tox studies, is elaborated. The literature search was conducted using PubMed, Web of Science, Scopus, UpToDate, Cochrane Library, Embase, and Google Scholar, covering relevant studies published up to December 2024.
The integration of secukinumab into HS treatment highlights the critical role of targeting the IL-17A pathway. Although efficacious and safe in trials, understanding secukinumab's long-term effects and optimal treatment placement remains challenging. Future research should prioritize the development of tailored therapeutic strategies that align with individual disease phenotypes and immune profiles to enhance treatment outcomes in HS management.
化脓性汗腺炎(HS)是一种慢性皮肤病,对患者生活质量有重大影响,凸显了创新治疗方法的必要性。HS的特点是具有慢性病程;表现为疼痛性结节、脓肿以及窦道或瘘管,通常局限于皮肤褶皱部位,在成年早期发病,且主要见于女性人群。
在本综述中,作者讨论了司库奇尤单抗用于HS的临床前发现与开发,重点介绍了靶点识别、验证及化合物选择。探讨了诸如高内涵筛选、化学信息学以及验证白细胞介素-17(IL-17)通路在HS中作用的动物模型等方法。阐述了从临床前到临床开发的转变,包括药代动力学(PK)、药效动力学(PD)以及药物代谢动力学-毒理学(ADME-Tox)研究。文献检索使用了PubMed、科学网、Scopus、UpToDate、考克兰图书馆、Embase和谷歌学术,涵盖截至2024年12月发表的相关研究。
将司库奇尤单抗纳入HS治疗突出了靶向IL-17A通路的关键作用。尽管在试验中有效且安全,但了解司库奇尤单抗的长期影响和最佳治疗定位仍具有挑战性。未来研究应优先开发与个体疾病表型和免疫特征相匹配的定制治疗策略,以提高HS管理中的治疗效果。