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

Psoriatic arthritis (PsA) is a chronic systemic inflammatory disease charac-terised by high phenotypic heterogene-ity. Peripheral polyarticular, pauciar-ticular, 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 sig-nificantly impacted the quality of life of patients with PsA even though a signifi-cant 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 patho-physiological 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 periph-eral PsA and their positioning in the context of EULAR/GRAPPA guidelines.