Biologics that inhibit the Th17 pathway and related cytokines to treat inflammatory disorders

ABSTRACT

Introduction: Advances in the understanding of TNF-α and IL-17 synergistic functions have recently led to the concept that patients who do not respond or who respond inadequately to TNF-α inhibitors may have IL-17-driven diseases, opening up the way for a new class of therapeutic development: Th17-inhibitors.

Areas covered: In this review, the authors discuss the central role that the IL-23/Th17 axis plays in the pathogenesis of several inflammatory diseases, such as psoriasis, highlighting its position as a relevant therapeutic target. In particular, the authors start by giving a brief historical excursus on biologic agent development up until the success of TNF-α inhibitors, and continue with an overview of IL12/23 pathway inhibition. Next, they describe Th17 cell biology, focusing on the role of IL-17 in host defense and in human immune-inflammatory diseases, discussing the use and side effects of IL-17 inhibitors.

Expert opinion: The IL-23/Th17 signaling pathway plays a central role in the pathogenesis of several inflammatory diseases, such as psoriasis. Recent data has demonstrated that biologics neutralizing IL-17 (ixekizumab, secukinumab) or its receptor (brodalumab) are highly effective with a positive safety profile in treating moderate to severe psoriasis, offering new treatment possibilities, especially for patients who do not respond adequately to anti-TNF-α therapies.

KEYWORDS:

• Biological therapies
• anti-TNF-α
• anti-IL12/23
• anti-IL17
• immune-mediated diseases

Article highlights

• The development of therapies that target specific cytokines involved in inflammatory disease have increased our understanding of the pathogenesis of these diseases offering, at the same time, successful treatments.

• Anti-TNF-α agents were employed, at first, in the fields of rheumatology and gastroenterology but has now translated to dermatology and oncology.

• The anti IL-12/23 FDA approval history represents a transitional phase for the use of biologics in that, unlike anti-TNFα drugs, they received their first approval in dermatology.

• Anti IL-17 agents, such as anti IL-12/23, are focused primarly on treating skin diseases and received first approval in dermatology.

• Current IL-12/23 and IL-17A inhibitors have confirmed the initial hypothesis that the IL-23- Th17 pathway is indispensable in promoting a number of immune-mediated diseases.

This box summarizes key points contained in the article.

Declaration of interest

F.Ayala has served as a speaker, consultant, advisory board member for, or has received research grants from: Abbott, Basilea Pharmaceutica Ltd., Janssen-Cilag, Merck Serono, Novartis, Schering–Plough and Wyeth while N Balato has served as a speaker, consultant, advisory board member for, or has received research grants from Abbott, Janssen-Cilag, Merck Serono, Schering–Plough and Wyeth. 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.

Additional information

Funding

This manuscript has not been funded.