Myositis specific autoantibody subtypes are associated with response to Janus kinase inhibitors in patients with juvenile dermatomyositis

Objectives To evaluate the efficacy and safety of Janus kinase inhibitors (JAKi) in a monocentric series of patients with juvenile dermatomyositis (JDM) and to identify factors associated with the achievement of clinically inactive disease (CID). Methods Single-centre retrospective study of 39 JDM patients treated with JAKi fot at least 6 months. The proportion of patients achieving CID within 6 months after initiation of JAKi was assessed using the PRINTO criteria and the Skin Disease Activity Score. Type 1 interferon (IFN) gene signature, serum IFN-α and IFN-β protein titres were measured as potential response biomarkers. Results 39 patients with JDM were included. Partial or complete CID was achieved in 32/39 (82%) patients after 6 months of treatment. In responders, the mean steroid dose decreased from 1 to 0 mg/kg/d (p= 0.001) and all other medications were withdrawn. In multivariable analysis, the presence of anti-TIF-1γ antibodies was the only factor at JDM onset associated with the absence of CID (p< 0,001. A significant decrease in the median Type 1 IFN score and serum IFN- α from the diagnosis of JDM to the 6-months follow-up was observed only in patientswith CID. JAKi-related adverse events consisted of infections in 9 patients (including 5 herpes zoster infections) and weight gain in 3 patients. Conclusions JAKi induced CID in the majority of new-onset and refractory JDM patients, except in a subset of patients with refractory TIF-1γ positive JDM. Overall tolerance was acceptable. These results need to be validated in a larger prospective international cohort study.