Target molecules for future hidradenitis suppurativa treatment

Area of Science:

• Dermatology
• Immunology
• Pharmacology

Background:

• Adalimumab, a tumor necrosis factor-α inhibitor, was approved for hidradenitis suppurativa (HS) in 2015, but its real-world effectiveness is variable.
• A significant unmet medical need persists for HS patients, driving the search for novel therapeutic targets.

Purpose of the Study:

• To review promising novel therapeutic targets for hidradenitis suppurativa (HS) discussed at the 10th European Hidradenitis Suppurativa Foundation (EHSF) e.V. Conference.
• To assess the pathophysiological and clinical potential of molecules under investigation for HS treatment.

Main Methods:

• Review of published data and ongoing clinical trial results for novel HS therapeutic targets.
• Discussion of molecules targeting interleukin (IL)-17, IL-1α, IL-36, Complement 5a (C5a), and Janus kinase (JAK) 1 signaling.

Main Results:

• Anti-IL-17 biologics (bimekizumab, secukinumab) and IL-1α targeting (bermekimab) show promising results in advanced clinical development.
• Targeting IL-36 (spesolimab) aligns with HS pathogenesis, with Phase II trials pending.
• C5a blockade offers benefit in severe HS, while JAK 1 inhibition requires careful dose-efficacy-safety monitoring.

Conclusions:

• Current novel HS treatments demonstrate modest clinical efficacy.
• Further translational data on HS pathogenesis are crucial for guiding future drug development.
• Continued investigation into targeted therapies is essential for addressing the unmet needs in HS management.