Emerging synthetic drugs for the management of hidradenitis suppurativa: a comprehensive update.

PMID 42342652 | DOI 10.1080/14656566.2026.2695100 · Expert opinion on pharmacotherapy · 2026

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INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic, debilitating inflammatory skin disorder affecting intertriginous regions. Despite its substantial impact on quality of life and association with serious systemic comorbidities, undertreatment remains a concern. Currently, only three biologic agents - adalimumab, secukinumab, and bimekizumab - hold regulatory approval for moderate-to-severe HS. A large proportion of patients, however, fail to achieve adequate or sustained responses, representing an urgent unmet therapeutic need for novel drugs. Among them, new, orally bioavailable, synthetic small-molecule agents are emerging. AREAS COVERED: This review synthesizes current evidence on emerging oral synthetic drugs for HS, drawn from PubMed, ClinicalTrials.gov, congress abstracts, and peer-reviewed publications through March 2026. Mechanistic classes discussed include Janus kinase (JAK) inhibitors (povorcitinib, upadacitinib, ruxolitinib), TYK2 inhibitors (brepocitinib, ropsacitinib, deucravacitinib), PDE-4 inhibitors (apremilast, orismilast, roflumilast), BTK/SYK inhibitors (remibrutinib, fostamatinib), IRAK-4 inhibitors (zimlovisertib), and HSP-90 inhibitors (RGRN-305). EXPERT OPINION: Oral JAK1 inhibition represents the most advanced small-molecule strategy for HS treatment. The emergence of topical JAK inhibitors (ruxolitinib cream) for milder HS and the progression of BTK inhibitors (remibrutinib) to Phase 3 trials signal a broadening treatment landscape. Personalized selection of synthetic drugs versus biologics - informed by patient comorbidities, disease phenotype, and biomarkers - will be involved in next-generation HS management.