Ixekizumab for treatment of psoriasis

Abstract

Psoriasis is a prevalent chronic inflammatory skin disease of unknown etiology. Recent advances in understanding the pathogenesis of psoriasis suggest that IL-17 is a key proinflammatory mediator present in the skin. Several agents targeting IL-17 or its receptor are in clinical trials for the treatment of psoriasis. This review focuses on the biological rationale and the results of clinical trials with ixekizumab, a humanized IgG4 monoclonal antibody. Ixekizumab binds the IL-17A homodimer, thereby blocking the binding of IL-17A to the IL-17 receptor. The currently available Phase I–III data indicate that ixekizumab is a promising drug, although long-term data of efficacy and safety are needed before ixekizumab and other IL-17 targeting therapeutics can find their place in clinical practice.

Keywords:

• IL-17A
• IL-17F
• IL-22
• ixekinumab
• psoriasis

Financial & competing interests disclosure

C Zachariae has received consultancy and/or speaker honoraria from Abbott, Pfizer and Takeda and is a member of Advisory Boards of AbbVie, Novartis, Eli Lilly, MSD, Amgen, Takeda and Janssen-Cilag. L Skov has received consultancy and/or speaker honoraria from Abbott, Pfizer, Janssen-Cilag, MSD and Leo Pharma and is a member of the Advisory Boards of MSD, Novartis, Eli Lilly, Abbvie, Celgene, Amgen and Janssen-Cilag. 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.

No writing assistance was utilized in the production of this manuscript.

Key issues

• IL-17A is a key mediator of the immune pathology observed in psoriasis.

• Three new biologic drugs targeting the IL-17 pathway are in clinical development for psoriasis treatment.

• Ixekizumab is a humanized IgG4 monoclonal antibody that binds the IL-17A homodimer and IL-17A/F heterodimer, thereby blocking the binding of IL-17A to the IL-17 receptor.

• Clinical trials with ixekizumab on patients with moderate-to-severe psoriasis have shown encouraging results.