Evolving the HS Treatment Paradigm, Long-Term Outcomes with IL-17 Inhibition - Episode 10
Exploring the Role of JAK Inhibitors in HS
Panelists discuss how JAK inhibitors show promise for specific HS phenotypes, including patients with milder disease with inflammatory nodules, those with severe trunk/buttock disease, and systemically ill patients, and may work synergistically with IL-17 inhibitors in combination therapy for the most severe cases without additive infection risk.
Janus kinase (JAK) inhibitors represent an emerging therapeutic class for hidradenitis suppurativa (HS), with phase 3 trials showing approximately 50% of patients achieving HiSCR75, positioning these oral medications as valuable additions to the treatment armamentarium. Clinical experience suggests JAK inhibitors may excel in specific patient subpopulations, including those with predominantly inflammatory nodular disease without extensive tunneling, and men with severe trunk and buttock involvement resembling a Crohn-like phenotype with multiple fistulas. Patients with significant systemic symptoms including weight loss, elevated metabolic activity, and persistent feverlike symptoms may benefit from JAK inhibitors’ broader immunologic effects.
The most exciting application of JAK inhibitors involves combination therapy with IL-17 inhibitors for patients with the most severe disease that fails monotherapy with any single agent. Early clinical experience suggests this combination maintains favorable safety profiles similar to those of the individual agents without the exponentially increased infection risk observed when combining TNF inhibitors with JAK inhibitors. This synergistic approach addresses the reality that trial exclusion criteria limiting draining tunnel counts mean many patients with the most severe disease never qualified for pivotal studies, yet they represent the population with greatest unmet need.
Multiple JAK inhibitors with varying selectivity profiles are in development for HS, offering potential advantages in terms of established safety databases from use in other indications and broad availability across multiple inflammatory conditions. The oral administration route provides practical advantages for some patients, though the classwide safety considerations familiar to dermatologists from use in other conditions require careful patient selection and monitoring. As more data emerge, JAK inhibitors may find specific niches based on patient phenotype, disease pattern, and treatment history.
