A Systematic Review of the Use of Janus Kinase Inhibitors in Large Vessel Vasculitis

Janus kinase inhibitors (JAKi) are emerging agents in the treatment of rheumatological diseases. Their role in rheumatoid arthritis and spondyloarthropathies has been established. The treatment of Takayasu Arteritis (TAK) and Giant Cell Arteritis (GCA) is large vessel vasculitis requiring long courses of glucocorticoids, often combined with other immunosuppressants. It has been shown that the pathogenesis of TAK and GCA involves the JAK-signal transducer and activator of transcription (STAT) pathway, showing that JAKi can theoretically be efficacious in these conditions. A systematic review of the use of JAKi in TAK and GCA is conducted across six databases: PubMed, PubMed Central, Google Scholar, EMBASE (via OVID), Science Direct, and Cochrane Library. Studies in the English language and human studies from 2019 to 2024 on the efficacy and safety of JAKi in patients with GCA or TAK were included. Pre-clinical, in-vitro, animal studies, or studies in which patients have other concomitant autoimmune diseases, malignancies, or prior exposure to JAKi are excluded. In total, 19 studies were included, of which six were cohort studies and seven were case reports for TAK. For GCA, three cohort studies, two case reports and one double-blind randomized controlled trial (RCT) were identified. One case report involves an overlap between TAK and GCA, but apart from older age, the patient only had TAK features. Abstracts and patients with other concomitant autoimmune diseases or malignancies were excluded. Upadacitinib, tofacitinib, baricitinib, and ruxolitinib were the JAKi studied. Of the cohort studies, two included a comparison group with traditional immunosuppressants, namely, methotrexate and leflunomide, and both were in TAK. All case reports were about patients with refractory disease. The only RCT was done with GCA patients using upadacitinib 15mg daily vs 7.5mg daily vs placebo. Most studies and case reports demonstrated the effectiveness of JAKi in the outcomes measured, namely, clinical activity, symptoms or signs, imaging findings, inflammatory marker levels, disease relapse, and corticosteroid requirement. JAKi are also generally safe, with infections being the most common adverse effect. This review is limited by the fact that most studies do not have a controlled group and that the different definitions of disease remission, relapse, or refractoriness are adopted across different studies. Thus, future studies addressing these limitations are needed.