Target molecules for future hidradenitis suppurativa treatment

Christos C. Zouboulis*, John W. Frew, Evangelos J. Giamarellos-Bourboulis, Gregor B.E. Jemec, Veronique del Marmol, Angelo V. Marzano, Georgios Nikolakis, Christopher J. Sayed, Thrasyvoulos Tzellos, Kerstin Wolk, Errol P. Prens

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Scopus)

Abstract

The registration of the tumour necrosis factor-α inhibitor adalimumab in 2015 was a major step forward in the treatment of hidradenitis suppurativa/acne inversa (HS). However, it soon became evident that the effectiveness of adalimumab in daily practice was highly variable. A significant unmet medical need of HS patients remained, and the search for novel therapeutic targets was intensified. During the 10th European Hidradenitis Suppurativa Foundation (EHSF) e.V. Conference, reknown international HS investigators virtually presented and discussed the published data on these potential target molecules for future HS treatment. This article addresses the most promising molecules currently under investigation from a pathophysiological and clinical point of view. With phase III trials ongoing, the anti- interleukin (IL)-17 biologics bimekizumab and secukinumab are in the most advanced stage of clinical development showing promising results. In addition, targeting IL-1α with bermekimab has shown encouraging results in two clinical trials. Directing treatment at neutrophil recruitment and activation by targeting IL-36 with spesolimab fits well in the pathogenic concept of HS and clinical phase II trial results are pending. In contrast to in situ evidence, Complement 5a (C5a) and C5a receptor blockade have only shown greater clinical benefit in patients with severe HS. Inhibition of Janus kinase (JAK) 1 signalling in HS showed clinical efficacy only in the highest dosage, highlighting that careful surveillance of the balance between safety and efficacy of JAK inhibition is warranted. Overall, clinical efficacies of all novel treatments reported so far are modest. To guide drug development, more and better-defined translational data on the pathogenesis of this severe and enigmatic inflammatory skin disease are required.

Original languageEnglish
Pages (from-to)8-17
Number of pages10
JournalExperimental Dermatology
Volume30
Issue numberS1
DOIs
Publication statusPublished - Jun 2021

Bibliographical note

Funding Information:
The Department of Dermatology, Zealand University Hospital, Roskilde, Denmark; the Department of Dermatology, H?pital Erasme, Universite Libre de Bruxelles, Bruxelles, Belgium; the Department of Dermatology, Erasmus University Medical Center Rotterdam, Rotterdam, Netherlands; and the Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane, Dessau, Germany are health care providers of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin ? ALLOCATE Skin group).

Funding Information:
All authors declare that none of the mentioned conflicts of interest had any influence to this manuscript. CCZ has received thematically relevant honoraria from Incyte, Inflarx, Janssen‐Cilag, Novartis, Regeneron and UCB as advisor. His departments have received grants from AbbVie, AOTI, Astra Zeneca, Galderma, Inflarx, Naos‐Bioderma, Novartis, PPM and UCB for his participation as clinical investigator. JWF was supported in part by a grant (no. UL1 TR001866) from the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) Program. EJG‐B has received honoraria from Abbott, Angelini, bioMérieux, InflaRx, MSD and XBiotech; independent educational grants from AbbVie, Abbott, Astellas, AxisShield, bioMérieux, InflaRx, ThermoFisher Brahms, and XBiotech; and funding from the FrameWork 7 program HemoSpec (granted to the National and Kapodistrian University of Athens), the Horizon2020 Marie‐Curie Project European Sepsis Academy (granted to the National and Kapodistrian University of Athens), and the Horizon 2020 European Grant ImmunoSep (granted to the Hellenic Institute for the Study of Sepsis). GBEJ has received honoraria from AbbVie, Chemocentryx, Coloplast, Incyte, Inflarx, Kymera Therapeutics, LEO, Novartis and UCB for participation on advisory boards, and grants from Abbvie, Astra‐Zeneca, Inflarx, Janssen‐Cilag, LEO, Novartis, Regeneron and Sanofi for participation as an investigator, and received speaker honoraria from AbbVie, Boehringer‐Ingelheim, Galderma and Novartis. He has also received unrestricted departmental grants from LEO and Novartis. VdM has received honoraria for advisory board participation from BMS, Leo Pharma, Sanofi. CJS has received honoraria as an investigator for AbbVie, Chemocentryx, Incyte, InflaRx, Novartis and UCB; consultancy fees from AbbVie, InflaRx; speaker for AbbVie, Novartis; and consulting fees paid to institution from UCB. TT reports fees from AbbVie, UCB and Sanofi (consultancy, speaker honorarium). KW has received research grants, travel grants, consulting honoraria or lecturer honoraria from AbbVie, Biogen IDEC, Celgene, and Charité Research Organisation. EPP received honoraria from AbbVie, Amgen, Celgene, Galderma, Janssen‐Cilag, Novartis and Pfizer for participation as a speaker and serving on advisory boards and investigator‐initiated grants (paid to the Erasmus MC) from AbbVie, AstraZeneca, Janssen‐Cilag and Pfizer. AVM and GN declare no conflict of interest.

Publisher Copyright:
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

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