JAK Inhibitors for the Treatment of Axial Spondyloarthritis.

Abstract

Axial spondyloarthritis (axSpA) is a chronic disease characterized by inflammation and new bone formation that causes pain and results in functional impairment and long-term disability. Biologic agents targeting TNFα or IL-17 have been the mainstay of treatment for patients with axSpA and an inadequate response to nonsteroidal anti-inflammatory drugs. However, a proportion of axSpA patients do not respond adequately to those drugs either, creating the need to target alternative disease pathways. Janus kinase (JAK) inhibitors (JAKis) are a group of targeted synthetic disease-modifying anti-rheumatic drugs that block the intracellular signalling pathway of several proinflammatory cytokines. Given their efficacy in the management of rheumatoid arthritis and that JAKs mediate the signalling of cytokines involved in the pathogenesis of axSpA as well, JAKis have been successfully tested in a number of clinical trials in axSpA, which has led to the approval of two compounds, tofacitinib and upadacitinib for the treatment of the disease. Data from new clinical trials, long-term extensions of completed trials, and real-life observational studies that continuously emerge will shape the efficacy and safety profile and ultimately the place of JAKis in the treatment of AxSpA.