Role of the IL-23 pathway in the pathogenesis and treatment of enthesitis in psoriatic arthritis

ABSTRACT

Introduction

Enthesitis is a key feature of spondyloarthritis (SpA). Several studies have underlined the role of interleukin (IL)-23 in SpA development as a crucial cytokine in the pathogenesis of enthesitis.

Area covered

This review summarizes recent evidence of the role of IL-23 in the pathogenesis of and as a target of the treatment of enthesitis. We review the definition, diagnosis and clinical impact of enthesitis and its connection with microbial infections, gut dysbiosis, and mechanical stress. We also review clinical trials and real-life studies of drugs targeting the p19 or p40 subunits of IL-23.

Expert opinion

Novel therapies targeting the p19 or p40 subunit of IL-23 appear to be promising treatment options for patients with enthesitis. Although we are currently unable to identify the best therapeutic window to target IL-23 in SpA disease evolution, the promising ability of this therapy to control the gut-entheseal axis is increasing our knowledge of SpA pathogenesis.

KEYWORDS:

• Enthesitis
• interleukin-23
• pathogenesis
• psoriatic arthritis
• spondyloarthritis
• treatment

Article highlights

• Enthesitis is the hallmark of all spondyloarthritis (SpA) phenotypes, including psoriatic arthritis (PsA), ankylosing spondylitis, reactive arthritis, inflammatory bowel disease-associated SpA, and undifferentiated phenotypes.

• Interleukin (IL)-23 is important in the development of SpA and one of the key proinflammatory cytokines involved in the pathogenesis of enthesitis.

• SpA patients have an altered genetic landscape, favoring an amplified signaling of IL-23.

• Gut dysbiosis may represent the starting point for local activation of the immune system, mainly through the IL-23/IL-17 axis.

• IL-23 favors the differentiation of T-helper (Th)17 and Th22 lymphocytes, which can recirculate and migrate to entheseal sites promoting inflammation and bone remodeling. Entheseal mechanical stress may further amplify this process, due to the aberrant development of neo-vessels and local recruitment of immune cells producing or responding to IL-23.

• Clinical trials and real-life studies have demonstrated that drugs targeting the p19 or p40 subunit of IL-23 are promising in the treatment of patients with enthesitis.

• The use of inhibitors which target the IL-23 pathway could represent a valid treatment option for PsA-related enthesitis.

This box summarizes key points contained in the article.

Acknowledgments

Editorial support and assistance was provided by Lorenza Lanini and Melanie Gatt, independent medical writers, on behalf of Springer Healthcare.

Declaration of interest

M Rossini has received advisory board honoraria, consultancy fees and/or speaker fees from Abiogen, Amgen, Abbvie, BMS, Celgene, Eli-Lilly, MSD, Novartis, Pfizer, Sanofi, Sandoz, and UCB. 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

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was sponsored through an unconditional contribution of Janssen, without any intervention or influence in the development of the contents reported. Medical writing assistance was used for the preparation of this manuscript, funded by Janssen.