JAK Inhibitors in Rheumatoid Arthritis

Abstract

JAK inhibitors (JAKi) are targeted, small-molecule, disease-modifying therapies that are the newest class of treatments to emerge for the management of rheumatoid arthritis (RA) and the first oral disease-modifying anti-rheumatic drugs (DMARD) to demonstrate comparable clinical efficacy to biological DMARDs (bDMARD). In the UK there are four JAKi licensed for the treatment of RA (baricitinib, tofacitinib, upadacitinib, and filgotinib) and recent years have seen an explosion in their use. Clinical trial evidence supports their efficacy in a range of RA cohorts including DMARD-naïve patients and those with treatment-refractory disease. JAKi are associated with increased risk for infection, particularly herpes zoster virus reactivation, cytopenias, and hyperlipidaemia. In older patients with cardiovascular risk factors, post-marketing data suggest increased risk for malignancy, venous thromboembolism (VTE), and major cardiovascular events (MACE) with JAKi. This review article discusses the mechanism of action of JAKi and the evidence for their efficacy and side effect profile.