Updates in juvenile dermatomyositis: pathogenesis and therapy.

PURPOSE OF REVIEW: This review provides updates on juvenile dermatomyositis pathogenesis and treatment.

RECENT FINDINGS: JDM pathogenesis research updates in genetic risk factors include C4 copy number. Studies clarify myositis-specific autoantibodies' (MSA) role in disease pathogenesis and more myositis-associated antibody (MAA) clinical associations. Recent studies validate an interferon (IFN)-regulated gene score and an IFN-related monocyte surface protein marker, SIGLEC-1. Vasculopathy and mitochondrial dysfunction evidence increases, both with ties to IFN. Studies point to not only T and B cells, but monocytes, macrophages, and neutrophils as dysregulated in JDM. Regarding treatment, there are growing reports of success with therapies targeting IFN-signaling (Janus kinase inhibitors), dazukibart (anti-IFN-beta), and anifrolumab (anti-IFNAR1). Chimeric antigen receptor (CAR) T-cell therapy targeting B-cells in a growing number of adult myositis patients and one JDM patient have dramatic reports of achieving drug-free remission.

SUMMARY: Growing evidence show genetic markers, MSA, IFN, vasculopathy, varied immune cells, and mitochondrial dysfunction having important roles in JDM pathogenesis. Some refractory patients show benefit with newer IFN pathway-targeted therapies and cellular CAR-T-cell therapy. Further collaborative research on disease pathogenesis, treatment targets, and innovate clinical trial design is needed to increase access to more efficacious treatments in JDM.