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 a high unmet medical need. The prevalence of HS reported in most studies is 1-2%, although it is likely to be under-reported and estimates vary globally owing to variance in data collection methods, ethnicity, geographical location and under-diagnosis. 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 tumour necrosis factor (TNF)-α and interleukin (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 and hormonal therapies; and various surgical procedures. The anti-TNF-α antibody adalimumab is currently the only biologic approved by both the US Food and Drug Administration and the European Medicines Agency for HS; however, its efficacy varies, with a clinical response reported in approximately 50% of patients in phase III 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 recently emerged, and agents targeting the IL-17 and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways are the most advanced in ongoing or completed phase III 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.
Competing Interests: Conflicts of interest J.G.K. has been a consultant and/or received honoraria from AbbVie, Aclaris Therapeutics, Allergan, Almirall, Amgen, Arena, Aristea, Artax Biopharma, Asana, Aurigene, Biogen Idec, Boehringer Ingelheim, Bristol Myers Squibb, Escalier, Galapagos, Janssen, Kyowa Kirin, Lilly, MoonLake Immunotherapeutics, Nimbus, Novartis, Pfizer, Sanofi, Sienna Biopharmaceuticals, Sun Pharma, Target-Derm, UCB, Valeant and Ventyx Biosciences. J.F. has conducted advisory work for Janssen, Boehringer Ingelheim, Pfizer, Kyowa Kirin, LEO Pharma, Regeneron, ChemoCentryx, AbbVie and UCB; participated in trials for Pfizer, UCB, Boehringer Ingelheim, Eli Lilly and CSL; and received research support from Ortho Dermatologics and Sun Pharma. G.B.E.J. reports grants and/or personal fees from AbbVie, Coloplast, ChemoCentryx, LEO Pharma, LEO Foundation, AFYX, Incyte, InflaRx, Janssen-Cilag, Novartis, UCB, CSL Behring, Regeneron, Sanofi, Kymera and Viela Bio. A.B.K.’s institution received grants from AbbVie, Admirx, AnaptysBio, Aristea, Bristol Myers Squibb, Eli Lilly, Incyte, Janssen, MoonLake Immunotherapeutics, Novartis, Pfizer, UCB and Sonoma Bio. A.B.K. has received consulting fees from AbbVie, Alumis, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, FIDE, Janssen, MoonLake Immunotherapeutics, Novartis, Pfizer, Priovant Therapeutics, Sonoma Bio, Sanofi, UCB, Target RWE and Ventyx Biosciences; royalties from BIDMC; holds stock in Ventyx Biosciences; and serves on the board of directors of Almirall. B.K. has acted as an investigator or received grants and/or honoraria from AbbVie, Almirall, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Celgene, Janssen, Lilly, LEO Pharma, Merck, MoonLake Immunotherapeutics, Novartis, Pfizer and UCB Pharma. F.G.B. has received honoraria for participation in advisory boards, in clinical trials and/or as a speaker from AbbVie, AbbVie Deutschland, Boehringer Ingelheim Pharma, Novartis Pharma, UCB Pharma, Incyte, MoonLake Immunotherapeutics, Mölnlycke and Janssen-Cilag. K.N. declares no conflicts of interest. E.P. has served as a consultant, advisory board member, speaker, Principal Investigator and/or received research grants from AbbVie, Bristol Myers Squibb, Celgene, CHDR, Citryll, ChemoCentryx, Galderma, GSK, InflaRx, Janssen-Cilag, Kymera, Novartis and UCB. K.R. has served as an advisor and/or paid speaker for and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Forward Pharma, Gilead, Galderma, Janssen-Cilag, Kyowa Kirin, LEO Pharma, Lilly, Medac, Novartis, Ocean Pharma, Pfizer, Sanofi and UCB. K.R. is co-founder and an employee of MoonLake Immunotherapeutics (Zug, Switzerland). E.C. is an employee of MoonLake Immunotherapeutics (Zug, Switzerland). K.W. has received research grants, travel grants, consulting honoraria or lecturer’s honoraria from AbbVie, AbbVie Deutschland, Celgene/BMS, Charité Research Organisation, Dr. Willmar Schwabe, Flexopharm, Janssen-Cilag, Novartis Pharma, Pfizer Deutschland, Sanofi-Aventis Deutschland, TFS and UCB Biopharma.
(© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)