Evolving the HS Treatment Paradigm, Long-Term Outcomes with IL-17 Inhibition - Episode 5
Role of IL-17 Inhibition in HS
Panelists discuss how IL-17 emerged as a key inflammatory driver in HS pathophysiology, with IL-17 inhibitors offering strong efficacy and favorable safety profiles compared with TNF inhibitors, making them increasingly preferred as first-line biologic therapy except in patients with inflammatory bowel disease.
IL-17 emerges as a key cytokine driver in hidradenitis suppurativa (HS) pathophysiology, though the disease involves multiple inflammatory pathways, including innate and adaptive immunity with contributions from Th17 cells, B cells, and neutrophils. The understanding of IL-17’s role evolved partially through therapeutic success, as the efficacy of IL-17 inhibitors in treating HS confirmed this cytokine pathway’s importance in disease mechanisms. Early studies demonstrated elevated IL-17 levels in both tissue samples and serum from patients with HS, supporting the rationale for targeting this pathway with biologic therapy.
IL-17 inhibitors have become first-line treatment for many practitioners due to their favorable safety profile compared with TNF inhibitors, particularly the absence of tuberculosis reactivation risk and lower rates of serious infections. The mechanism differs slightly between available agents: Secukinumab targets IL-17A alone, while bimekizumab blocks both IL-17A and IL-17F, potentially offering broader pathway inhibition with corresponding differences in efficacy and adverse effect profiles. The dual IL-17A/F inhibition may provide more rapid response and greater impact on drainage, particularly from abscesses and tunnels, though it carries slightly higher risk of cutaneous adverse effects.
Clinical decision-making around IL-17 inhibitor selection considers multiple patient factors including disease severity, comorbidities (particularly inflammatory bowel disease, which represents a contraindication), and patient preferences regarding adverse effect profiles. For patients with very severe disease, practitioners may prioritize agents with potentially more aggressive efficacy despite increased risk of manageable cutaneous reactions, while milder cases might favor medications with better tolerability profiles. The key exception to first-line IL-17 use involves patients with inflammatory bowel disease, for whom TNF inhibitors remain the preferred biologic approach.
