New insights into IFN-γ in rheumatoid arthritis: role in the era of JAK inhibitors

The treatment of rheumatoid arthritis (RA) is now entering a new era, the era of Janus kinase (JAK) inhibitors. JAK inhibitors target multiple cytokines including IL-6 and exhibit a beneficial treatment effect in patients with RA and inadequate response to conventional synthetic or biologic disease-modifying anti-rheumatic drugs. Since the treatment effect of JAK inhibitors is promising even for patients refractory to anti-IL-6 therapy, it needs to be considered how multiple cytokines play roles in the pathogenesis of RA. It is also worth noting that an increased risk of herpes zoster is specifically related to the use of JAK inhibitors. Among cytokines targeted by JAK inhibitors, the current review focuses on IFN-γ, particularly on its role in synovial biology, autoimmunity, bone metabolism, pain, and varicella zoster virus infection. Recent studies provided new insights into IFN-γ in the pathogenesis of RA, which may account for the efficacy of JAK inhibitors.