Hidradenitis suppurativa: New insights into disease mechanisms and an evolving treatment landscape.

Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic disabling and debilitating inflammatory disease with high unmet medical need. The prevalence of HS is 1-2% in most studies, although it is likely underreported and estimates vary globally due to variance in data collection methods, ethnicity, geographical location, and underdiagnosis. HS is characterized by persistent, painful cutaneous nodules, abscesses, and draining tunnels commonly affecting the axillary, anogenital, inguinal, and perianal/gluteal areas. Over time, chronic uncontrolled inflammation results in irreversible tissue destruction and scarring. Although the pathophysiology of HS has not been fully elucidated, the TNF-α and IL-17 pathways have an important role, involving multiple cytokines. Currently, treatment options include topical medications, systemic therapies including repeated and/or rotational courses of systemic antibiotics, retinoids, hormonal therapies, and various surgical procedures. The anti-TNF-α antibody adalimumab is currently the only biologic approved by both the Food and Drug Administration and the European Medicines Agency for HS; however, efficacy is varied, with clinical response reported in ∼50% of patients in Phase 3 trials. HS is a rapidly evolving field of discovery, with a diverse range of agents with distinct mechanisms of action currently being explored in clinical trials. Several other promising therapeutic targets have emerged recently, and agents targeting the IL-17 and JAK-STAT pathways are the most advanced in ongoing or completed Phase 3 clinical trials. Alongside limited therapeutic options, significant challenges remain in terms of diagnosis and disease management, with a need for better treatment outcomes. Other unmet needs include significant diagnostic delays, thus missing the therapeutic 'window of opportunity'; the lack of standardized outcome measures in clinical trials; and the lack of established, well-defined disease phenotypes and biomarkers.