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Perspectives of JAK Inhibitors for Large Vessel Vasculitis.
Vasculitis is an inflammation of the blood vessels caused by autoimmunity and/or autoinflammation, and recent advances in research have led to a better understanding of its pathogenesis. Glucocorticoids and cyclophosphamide have long been the standard of care. However, B-cell depletion therapy with rituximab has become available for treating antineutrophil cytoplasmic antibody-associated vasculitis (AAV). More recently, avacopan, an inhibitor of the complement 5a receptor, was shown to have high efficacy in remission induction against AAV. Thus, treatment options for AAV have been expanded. In contrast, in large vessel vasculitis (LVV), including giant cell arteritis and Takayasu arteritis, tocilizumab, an IL-6 receptor antagonist, was shown to be effective in suppressing relapse and has steroid-sparing effects. However, the relapse rate remains high, and other therapeutic options have long been awaited. In the last decade, Janus kinase (JAK) inhibitors have emerged as therapeutic options for rheumatoid arthritis (RA). Their efficacy has been proven in multiple studies; thus, JAK inhibitors are expected to be promising agents for treating other rheumatic diseases, including LVV. This mini-review briefly introduces the mechanism of action of JAK inhibitors and their efficacy in patients with RA. Then, the pathophysiology of LVV is updated, and a rationale for treating LVV with JAK inhibitors is provided with a brief introduction of our preliminary results using a mouse model. Finally, we discuss the newly raised safety concerns regarding JAK inhibitors and future perspectives for treating LVV.
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