Long-term follow-up of Janus-kinase inhibitor and novel active disease biomarker in juvenile dermatomyositis

Abstract

Objective To evaluate the use of Janus kinase inhibitor (JAKi) in treating JDM and develop cytokine biomarkers of active disease. Methods This study involved a retrospective cohort study that evaluated JAKi in 101 JDM patients as well as a cross-sectional study of cytokines in 128 JDM patients and 30 controls between November 2017 and December 2021 in the Affiliated Children's Hospital of Capital Institute of Pediatrics (China). Results During the median follow-up period of 19 months, 65.5% of the patients improved rashes, and CAT-BM scores decreased. 39.6% of JDM patients eliminated glucocorticoids. Muscle strength was improved in all patients who had abnormal muscle strength before JAKi use. Patients and parents provided positive subjective reviews of JAKi, and no serious adverse events were reported. Potential side effects of JAKi included abnormal leukopenia (14/95) and cough (16/83), which affected over 10% of the JDM patients. In the cytokine analysis, 12/34 cytokines were significantly elevated in active JDM patients. Compared with active JDM patients with multiple phenotypes, active JDM patients with only rashes demonstrated lower cytokine levels. Anti-NXP2-positive active patients had lower cytokine levels compared with those without positive anti-NXP2 antibodies. Among all increased cytokines, IL-1RA changed most dramatically, reaching over 793 times the mean of normal values. We developed a panel composed of 6 cytokines to differentiate active or stable status in our cohort (AUC = 0.8486, P < 0.05). Conclusion The preliminary evidence suggested that JAKi is a relatively safe and effective alternative for JDM patients. Cytokine profiles could well reflect the inflammatory status of JDM patients.

Comparison of cytokine/chemokine profiles between dermatomyositis and anti-synthetase syndrome

“…Zhou et al ( 14 ) also reported higher serum levels of IL-1ra in anti-MDA5 DM when compared with ASS. It was proposed that elevated serum IL-1ra in anti-NXP2 DM might switch from a controlled and protective immune role to one in which this protein promotes inflammatory tissue damage in severe cases ( 49 ). Future research on the role of IL-1ra in anti-NXP2 DM may offer new insights for the detection and treatment of patients with DM.…”

Efficacy of Janus kinase inhibitor baricitinib in the treatment of refractory juvenile dermatomyositis complicated by calcinosis

“…No serious adverse events were reported (2). Anti-NXP2-positive patients showed higher inflammatory cytokines expression than anti-NXP2-negative patients, with a more severe disease course characterised by subcutaneous calcinosis and muscle contractures (2)(3)(4)(5). Our patient, also anti-NXP2 positive, suffered from a severe refractory JDM and even if serum cytokine dosage was not performed, her interferon signature assay revealed a notable upregulation.…”