The Effectiveness of Janus Kinase Inhibitors for the Management of Relapsing Takayasu Arteritis: A Spanish Real-World Study and Comprehensive Review of the Literature

Background: A significant proportion of individuals with Takayasu arteritis (TA) experience relapses notwithstanding standard treatment with glucocorticoids, and conventional synthetic or biologic disease-modifying antirheumatic drugs (DMARDs). As the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway contributes to the pathogenesis of TA, JAK inhibitors (JAKi) could represent a viable therapeutic alternative. This study assessed the effectiveness of JAKi in patients with relapsing TA within a real-world setting in a country with a low incidence of TA such as Spain and included a comprehensive review of the literature. Methods: we conducted a retrospective analysis of TA patients managed with JAKi for recurrent disease across three Spanish centers. Evaluated outcomes comprised clinical remission, clinical and analytical remission, glucocorticoid-sparing effect, improvement in imaging techniques, and adverse events. A systematic literature search was performed to identify further cases of TA treated with JAKi. Results: six patients (83.3% females) with a mean age 48.5 years and relapsing TA received JAKi therapy: baricitinib (n = 2); tofacitinib (n = 2), and upadacitinib (n = 2). Before JAKi therapy, all (100%) patients had received conventional synthetic immunosuppressants, and four (66.7%) biologics. Clinical remission was achieved in 2/6 (33.3%), 3/5 (60%), 3/5 (60%), 2/3 (66.7%), and 2/2 (100%) patients at 1, 3, 6, 12 and 18 months, respectively. Clinical + analytical remission was observed in 1/6 (16.7%), 2/5 (40%), 2/5 (40%), 2/3 (66.7%), and 2/2 (100%) patients, respectively. Two patients who underwent a follow-up PET/CT imaging showed partial improvement in both. After a median (IQR) follow-up of 9.5 (6.0–16.7) months, one (16.7%) patient discontinued the initial JAKi due to no improvement and one patient discontinued it because was diagnosed with tonsillar neoplasia. The literature search identified another 166 JAKi-treated TA cases with clinical improvement reported for the majority of them. Conclusions: this real-world analysis and literature review suggest that JAKi could be effective in the management of TA, including for those patients who have failed established glucocorticoid-sparing strategies.