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Review
. 2023 Oct 11;15(10):2450.
doi: 10.3390/pharmaceutics15102450.

IL-17 Inhibition: A Valid Therapeutic Strategy in the Management of Hidradenitis Suppurativa

Dalma Malvaso  1   2 , Laura Calabrese  1   3 , Andrea Chiricozzi  1   2 , Flaminia Antonelli  1   2 , Giulia Coscarella  1   2 , Pietro Rubegni  3 , Ketty Peris  1   2
Affiliations
Review

IL-17 Inhibition: A Valid Therapeutic Strategy in the Management of Hidradenitis Suppurativa

Dalma Malvaso et al. Pharmaceutics. .

Abstract

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a significant negative impact on the quality of life of patients. To date, the therapeutic landscape for the management of the disease has been extremely limited, resulting in a profound unmet need. Indeed, adalimumab, an anti-tumor necrosis factor (TNF)-α monoclonal antibody, is the only approved biologic agent for HS, obtaining a therapeutic response in only 50% of HS patients. Numerous clinical trials are currently ongoing to test novel therapeutic targets in HS. The IL-17-mediated cascade is the target of several biologic agents that have shown efficacy and safety in treating moderate-to-severe HS. Both bimekizumab and secukinumab, targeting IL-17 in different manners, have successfully completed phase III trials with promising results; the latter has recently been approved by EMA for the treatment of HS. The aim of this review is to summarize the current state of knowledge concerning the relevant role of IL-17 in HS pathogenesis, highlighting the key clinical evidence of anti-IL-17 agents in the treatment of this disease.

Keywords: CJM112; IL-17 inhibitors; bimekizumab; biologics; brodalumab; hidradenitis suppurativa; ixekizumab; izokibep; secukinumab; sonelokimab.

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Conflict of interest statement

K. Peris has served on the advisory board of or received honoraria for lectures and/or research grants from AbbVie, Almirall, Eli Lilly and Company, Galderma, Leo Pharma, Pierre Fabre, Novartis, Sanofi, Sun Pharma, and Janssen Pharmaceuticals. A. Chiricozzi has served as an advisory board member and consultant and has received fees and speaker’s honoraria from and/or has participated in clinical trials for AbbVie, Almirall, Bristol Myers Squibb, Leo Pharma, Eli Lilly and Company, Janssen Pharmaceuticals, Novartis, Pfizer, and Sanofi Genzyme. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

Figure 1
Figure 1
Pathogenic role of IL-17A in hidradenitis suppurativa.
Figure 2
Figure 2
Specific therapeutic agents in development for the treatment of hidradenitis suppurativa. Brodalumab, a fully human monoclonal antibody that specifically targets the Interleukin 17 Receptor A (IL17RA), inhibits the downstream signaling of multiple IL-17 family cytokines. Bimekizumab and CJM112 are humanized antibodies that inhibit the signaling of both IL-17A and IL-17F. Secukinumab is a fully human monoclonal antibody that selectively binds to IL17A homodimers or heterodimers. Sonelokimab is a trivalent nanobody composed of IL-17A, IL-17F, and albumin-binding domains, effectively blocking the IL-17A and IL-17F downstream pathways. Izokibep owns a triple-helical structure, enabling it to bind IL17A with high affinity, thereby functioning as a neutralizing IL-17A ligand. Abbreviations: IL, Interleukin.
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