Why targeted therapeutics have provided benefit in psoriasis: looking at IL-17 biology

ABSTRACT

Introduction

Psoriasis is an inflammatory, chronic and immune-mediated disease that can affect the skin and joints. Pro-inflammatory cytokines have a dominant role in the pathogenesis of this heterogeneous disease in which the IL-23/IL-17 axis plays a crucial role. The IL-17 family is involved in numerous processes such as immune defense, intestinal disorders and diseases of the central nervous system. In psoriasis, in particular, many cytokines belonging to the IL-17 family are involved in the inflammatory cascade underlying the disease.

Areas covered

The knowledge of the mechanisms and pathways behind psoriasis is crucial for the development of new target therapies. We focused on IL-17 biology in order to understand why biological drugs against this cytokine are an effective treatment for moderate to severe psoriasis. Clinical trials results of ixekizumab, brodalumab, secukinumab and bimekizumab have been presented.

Expert opinion

Il-17 inhibitors are a very fast and effective treatment against psoriasis; however, fungal infections can occur during their use, due to IL-17 biological functions. Therefore, it should be mandatory to choose the right patients to treat with these monoclonal antibodies in order to have a tailored target therapy for each patient.

KEYWORDS:

• Bimekizumab
• brodalumab
• interleukin-17
• ixekizumab
• psoriasis
• secukinumab

Article highlights

• Psoriasis is a chronic immune-mediated disease with a central role of some proinflammatory cytokines in its pathogenesis.

• IL-17 is a cytokine involved in numerous mechanisms such as host immune defense, inflammatory bowel diseases, central nervous system diseases and psoriasis.

• The interleukin 17 family is composed by 6 members, i.e. IL-17A, IL-17B, IL-17C, IL-17D, IL-17E (or IL-25) and IL-17F. IL-17A, IL-17C and IL-17F are the most involved in the pathogenesis of psoriasis and are also expressed in large quantities in typical skin lesions, joint synovium and enthesis of patients with arthropathic psoriasis.

• IL-17 is the target of several and very effective drugs currently used for psoriasis: ixekizumab, secukinumab, brodalumab and bimekizumab.

Acknowledgments

We thank Denis Mariano for English language editing

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed receiving research, speaking and/or consulting support from Eli Lilly and Company, GlaxoSmithKline/Stiefel, AbbVie, Janssen, Alovtech, vTv Therapeutics, Bristol-Myers Squibb, Samsung, Pfizer, Boehringer Ingelheim, Amgen Inc, Dermavant, Arcutis, Novartis, Novan, UCB, Helsinn, Sun Pharma, Almirall, Galderma, Leo Pharma, Mylan, Celgene, Valeant, Menlo, Merck & Co, Qurient Forte, Arena, Biocon, Accordant, Argenx, Sanofi, Regeneron, the National Biological Corporation, Caremark, Advance Medical, Suncare Research, Informa, UpToDate and the National Psoriasis Foundation; being a founder and majority owner of www.DrScore.com [drscore.com] and founder and part owner of Causa Research; and has stock in Sensal Health. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.