Biologics in Refractory Myositis: Experience in Juvenile Vs. Adult Myositis; Part II: Emerging Biologic and Other Therapies on the Horizon

The idiopathic inflammatory myopathies (IIM) until recently have been considered a heterogeneous broad group of six autoimmune muscle diseases. Initially, autoantibodies in IIM (including JDM) and CD8+ T cell-induced cytotoxicity (PM and IBM) were the predominant recognized etiopathology mechanisms used to classify myopathies. In the early late 1990's to 2000's, evolving understanding of the molecules such as interleukin (IL), tumor necrosis factor (TNF), interferon (IFN), and other cytokines as well as differences in response to therapies, has led IIM researchers to look beyond previous disease mechanisms. For decades the overexpression of Th1- associated cytokines (TNF-α, IFN-γ and IL-12) in the areas of inflammation in skin and muscle in IIM pointed to Th1 as the primary pathway for inflammation in myositis.However, in the last decade overexpression and elevated level of Th17-associated cytokines (IL-17, IL-22, and IL-6) were identified in the blood and the inflamed muscles of myositis patients. We also do not know how Th1 and Th2 cytokines work differently in diverse hosts, in different concentrations, in different inflammatory milieus, and in the presence or absence of each other or other adhesion/co-stimulatory molecules such as NF-κB. Also, several autoantibodies to intracellular organelles have been identified in myositis.In this review, we will discuss the most recent advances in IIM research and how that might bring new biologic therapies to market in the next 5-15 years to assist in the care of our most difficult IIM and JDM patients.