Anti IL-17 in psoriasis

ABSTRACT

Introduction: Psoriasis is a chronic, immune-mediated disease with significant associated comorbidities. Its pathogenesis is likely multifactorial, however, the interleukin-23/T helper 17 pathway has been identified as a critical axis in its pathogenesis. Interleukin-17A is the primary effector of this pathway and overexpression of IL-17A results in epidermal hyperplasia and an overly robust inflammatory response, resulting in the skin plaques and systemic inflammation seen in psoriasis. Targeted anti IL-17 therapies have demonstrated efficacy in the treatment of moderate-to-severe plaque psoriasis.

Areas covered: A PubMed search was conducted for relevant literature. Secukinumab, ixekizumab, and brodalumab are anti IL-17 inhibitors currently approved for the treatment of moderate-to-severe plaque psoriasis. The efficacy and safety data from key phase III clinical trials are reviewed here.

Expert opinion: By targeting a key mediator of the interleukin-23/T helper 17 pathway, IL-17 antagonists are an effective treatment for plaque psoriasis. It has demonstrated efficacy and a favorable safety profile in key phase III clinical trials. In addition to efficacy, IL-17 antagonists have also shown long-term maintenance of treatment response and a quick onset of action. The efficacy of IL-17 inhibitors in the treatment of moderate-to-severe psoriasis underscores the importance of the IL-23/Th17 pathway in the pathogenesis of psoriasis.

KEYWORDS:

• Biologics
• brodalumab
• IL-17
• interleukin-17 inhibitors
• ixekizumab
• psoriasis
• secukinumab

Article highlights

• IL-23/IL-17 pathway in critical axis in the pathogenesis of psoriasis, and IL-17A is the primary effector.

• Secukinumab and ixekizumab are monoclonal antibodies to IL-17A. Brodalumab is a monoclonal antibody to IL-17RA.

• IL-17 antagonists have demonstrated efficacy, long-term maintenance of treatment response, and a quick onset of action.

• Important side effects include increased risk of mucocutaneous candidiasis, neutropenia, and IBD exacerbations.

• Bimekizumab and M1096 are IL-17A and IL-17F antibodies currently in development.

Declaration of interest

T Bhutani has received research or grant funding from Eli Lilly, Janssen, Merck, Celgene and Regeneron. W Liao has received research or grant funding from Abbvie, Amgen, Janssen, Novartis, Pfizer, and Regeneron. 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.

Reviewer disclosures

A reviewer on this manuscript has disclosed participation as a PI/SI, advisor and/or invited speaker for Novartis, Leo, Lilly, Janssen, Abbvie and Almirall. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.