Peripheral arthritis in psoriatic arthritis: from immunopathogenesis to therapy with Janus kinase inhibitors

Psoriatic arthritis (PsA) is a chronic systemic inflammatory disease characterised by high phenotypic heterogeneity. Peripheral polyarticular, pauciarticular, axial, enthesitic, and dactylitic forms have been classically described, although it is not clear whether they all have the same pathophysiological mechanisms. Use of cytokine-targeted therapies in the last 20 years has significantly impacted the quality of life of patients with PsA even though a significant proportion of patients, regardless of the mechanism of action considered, remain non-responders, suggesting the need for better understanding of the pathophysiological basis of the disease to appropriately stratify patients and identify new therapeutic targets. The pre-clinical demonstration of the pathophysiological relevance of the JAK/STAT pathway in the pathogenesis of PsA and the emerging efficacy data from randomised controlled trials of JAK inhibitors in PsA patients have set the stage for a new pharmacological era in patients with PsA. In this review, we discuss the rationale for using approved JAK inhibitors for treatment of peripheral PsA and their positioning in the context of EULAR/GRAPPA guidelines.