Janus kinase inhibition (JAKi) therapy in refractory anti-synthetase syndrome: A retrospective cohort study

Objectives: To evaluate the efficacy and safety of Janus kinase inhibitors (JAKi) in the treatment of refractory antisynthetase syndrome (ASS) in real-world clinical settings. Methods: The medical records of all refractory ASS patients who were treated with JAKi from October 2020 to June 2023 were retrospectively reviewed. Results: Twenty patients were included, and all (100 %) patients had interstitial lung disease (ILD). After treatment with JAKi, 14 (70 %) of the refractory ASS patients showed significant improvement in clinical manifestations, including arthritis (56.3 % vs. 6.3 %, p = 0.002), rash (77.8 % vs. 27.8 %, p = 0.012), shortness of breath (55.6 % vs. 16.7 %, p = 0.039), cough (61.1 % vs. 11.1 %, p = 0.012). Improvement was noted for myalgia (50 % vs. 11.1 %, p = 0.016) and muscular weakness (61.1 % vs. 11.1 %, p = 0.012), while creatine kinase (CK) levels, which were abnormally elevated in five patients prior treatment, were significantly lowered (1096 f 1042.98 IU/L vs. 199.2 f 144.66 IU/L, p = 0.043). A decrease in levels of inflammatory markers, including erythrocyte sedimentation rate (ESR) (p = 0.001) and C-reactive protein (CRP) (p = 0.023) was observed in the patients. In ASS-ILD, the CT score reduced (188.75 f 69.67 vs. 156.35 f 74.62, p = 0.001). Furthermore, the glucocorticoid dose significantly reduced (21.42 f 13.26 mg vs. 11.32 f 8.59 mg; p = 0.001). Conclusions: JAKi were effective in most refractory ASS patients as evidenced by improved skin rash, myositis, and ILD. However, larger prospective controlled studies are required to evaluate its efficacy.