Emerging therapies in idiopathic inflammatory myopathies

Idiopathic inflammatory myopathies (IIM), also known as myositis, are a group of heterogeneous autoimmune diseases characterized by muscle inflammation and frequent involvement of extramuscular organs. Autoantibodies are present in approximately 70% of the patients. Despite treatment advances, management of IIM largely relies on empirical approaches and current treatment options lack robust evidence, with the exception of intravenous immunoglobulin (IVIg). Even with immunosuppressive therapy, up to 80% of the patients continue to experience ongoing disease activity, functional impairment and a significant reduced quality of life. Several challenges complicate the management of IIM, including rare occurrence, heterogeneity of the disease, systemic manifestations, higher prevalence of malignancies and the complexity of conducting large-scale clinical trials in rare diseases. Along with this, therapeutic development has long been hindered by an incomplete understanding of the disease pathogenesis. However, recent insights into the molecular and cellular mechanisms of IIM have revealed novel therapeutic targets. In this review, we will discuss the underlying immunopathogenesis of IIM, including the role of potentially pathogenic autoantibodies, B and T cells, the interferon (IFN) pathway and the complement system. We will also review current treatment strategies and provide an overview of emerging and promising new treatments tested in recently published clinical trials or ongoing clinical trials, including chimeric antigen receptor (CAR) T-cell therapy, T-cell engagers, T-cell targeting therapies, neonatal Fc receptor (FcRn) inhibitors, and small-molecule inhibitors targeting intracellular signaling molecules such as Janus kinases (JAKs), IFNs, and complement.