IL-23 inhibition for the treatment of psoriatic arthritis

ABSTRACT

Introduction

Psoriatic arthritis (PsA) is a complex, polygenic immune-mediated disease with varying clinical presentations involving the skin, nails, entheses, and axial/peripheral skeleton.

Areas covered

Pathophysiology of PsA with special focus on IL-23/IL-17 axis. Novel classes of targeted therapies for PsA. Pharmacologic properties, efficacy and safety of guselkumab, the only FDA approved agent from IL-23p19 inhibitor class. Data regarding other IL-23 inhibitors (Ustekinumab – an IL-12/IL-23p40 inhibitor, Risankizumab and Tildrakizumab – both IL23p19 inhibitors), in the treatment of PsA.

Expert opinion

There are seven classes of FDA-approved therapies for the treatment of PsA. IL-23p19 inhibitors are the newest class of medications that has shown efficacy and reasonable safety profile in the treatment of PsA in phase 2 and phase 3 studies; Guselkumab is the only FDA-approved biologic for PsA within this class . While no head-to-head studies of IL-23p19 inhibitors and other PsA targeted therapies are available, the efficacy of these agents on musculoskeletal system appears to be comparable to TNF-inhibitors (TNFi), and the efficacy on the skin appears to be comparable, or modestly superior to the IL-17 inhibitors (IL-17i). With a superior safety profile compared to TNFi and IL-17i, IL-23p19 inhibitors have the potential to become a first-line biologic in the treatment of PsA.

KEYWORDS:

• Psoriatic arthritis
• IL-23
• interleukin-23
• guselkumab
• risankizumab
• ustekinumab

Article highlights

• Psoriatic arthritis (PsA) is a complex, polygenic immune-mediated disease with a variable clinical presentation

• Seven classes of novel targeted therapies have been developed for the treatment of psoriatic arthritis

• IL-17 and IL-23 are important cytokines involved in the pathophysiology of spondyloarthropathies including psoriatic arthritis and are responsible for many clinical features

• IL-23 inhibitors are an emerging class of medications that have shown efficacy in the treatment of psoriatic arthritis

• Guselkumab, the only FDA approved IL-23 inhibitor for the treatment of psoriatic arthritis, has shown efficacy in controlling signs and symptoms of musculoskeletal (peripheral and axial arthritis, enthesitis and dactylitis) and skin manifestations of the disease while also having a tolerable safety profile

This box summarizes key points contained in the article.

Declaration of interest

A Deodhar acts as a consultant/advisory board member for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Glaxo Smith & Kline, Janssen, Novartis, Pfizer, UCB. A Deodhar receives research grants from AbbVie, Eli Lilly, Glaxo Smith & Kline, Novartis, Pfizer, 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

One of the peer reviewers on this manuscript has received consultancy/speaker’s honoraria from and/or participated in clinical trials sponsored by Abbvie, Almirall, Amgen, Baxalta, Biogen, Boehringer Ingelheim, Celgene, Gebro, Janssen, JS BIOCAD, Leo-Pharma, Lilly, Merck-Serono, MSD, Mylan, Novartis, Pfizer, Regeneron, Roche, Sandoz, Samsung-Bioepis, Sanofi, and UCB. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.