The preclinical discovery and development of secukinumab for the treatment of moderate-to-severe hidradenitis suppurativa

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.