Ustekinumab in the treatment of psoriatic arthritis: latest findings and clinical potential

Abstract

Ustekinumab (UST) is a fully human immunoglobulin G1κ (IgG1κ) monoclonal antibody against common sub-unit p40 of interleukin-12 (IL-12) and interleukin-23 (IL-23). IL-12 and IL-23 are essential components of the Th1 and Th17 inflammatory pathways, respectively, and are the key mediators of psoriasis. Psoriatic arthritis (PsA), an important systemic inflammatory disorder, has similar pathogenesis to psoriasis. Many of PsA patients do not respond to tumor necrosis factor (TNF) inhibitor therapy, highlighting the need for additional treatment modalities with distinct mechanisms of action. Also, many patients stop responding to these agents after a certain period of use. A significant number of patients have a recurrent course or a persistent disease process. To meet these challenges a new agent working on different inflammatory aspect of PsA is needed. UST has been demonstrated to be effective, safe on short-term use and convenient in the treatment of plaque psoriasis and PsA. Long-term safety is still a concern. Until recently, the exact role of UST in the management of PsA had not been very clear. This article reviews the mechanism of action, pharmacokinetics, efficacy, safety profile and the clinical potential of UST in patients with PsA. We also discuss the three major trials conducted to show the efficacy and safety of UST in PsA.