The role of IL-23 and the use of IL-23 inhibitors in psoriatic arthritis

Abstract

Background: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis characterised by musculoskeletal and extra-articular manifestations, most notably psoriasis. While the underlying pathogenetic mechanisms are not yet fully understood, a central role has been identified for the IL-23/IL-17 pathway. Objectives: We briefly describe the role of IL-23 in the pathogenesis of PsA and go on to describe the available anti-IL-23 agents and their place in the management of PsA. Methods: This is a narrative review of the current literature, focussing on the results of the phase 3 studies in PsA for the IL-12/23 p40 inhibitor ustekinumab and the more recent IL-23 p19 inhibitors guselkumab, risankizumab and tildrakizumab. Results: IL-23 triggers expression of IL-17 and other effector cytokines in a variety of cells, leading to tissue inflammation and injury. Targeting IL-23, particularly with p19 inhibitors, appears to be an effective and safe strategy for multiple clinical domains in PsA, most notably the skin, with some differences in efficacy emerging between these agents. Conclusion: The development of IL-23 inhibitors represents a significant advance in the management of psoriatic disease. In the absence of head-to-head studies, future data emerging from real-world experiences of individual IL-23 p19 inhibitors will help inform the use of these agents in relation to other biologics in PsA.