Antibody Therapies in Autoimmune Inflammatory Myopathies: Promising Treatment Options

Abstract

Abstract Inflammatory myopathies, including polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM), necrotizing myopathy (NM), antisynthetase syndrome (ASS) and overlap myositis (OM), in short myositis, are rare diseases. All forms of myositis have progressive muscle weakness in common, with each subtype characterized by different autoantibody profiles, histological findings and extramuscular manifestations. Due to better understanding of the pathogenesis of the muscle inflammation in myositis, new molecular pathways for targeted therapy have been discovered. Current therapies aim at different components of the innate or the adaptive immune response. Additionally, non-inflammatory mechanisms in myositis have come into focus as possible treatment targets. The use of therapeutical antibodies in myositis has been examined in various clinical studies, several of them randomized controlled ones: Depletion of B-cells by rituximab has been established as treatment of refractory myositis. IVIG, an antibody therapy in the wider sense, has now been licensed for DM following a recent positive clinical trial. Negative study results were reported in randomized trials with infliximab, sifalimumab and bimagrumab. Studies on basiliximab and eculizumab are currently underway, and are expected to yield results in a couple of years. Despite some promising results of clinical studies with antibody therapy in myositis, further research is crucial to optimize the treatment for this debilitating disease and to find treatment alternatives for treatment-refractory patients.

Abstract Inflammatory myopathies, including polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM), necrotizing myopathy (NM), antisynthetase syndrome (ASS) and overlap myositis (OM), in short myositis, are rare diseases. All forms of myositis have progressive muscle weakness in common, with each subtype characterized by different autoantibody profiles, histological findings and extramuscular manifestations. Due to better understanding of the pathogenesis of the muscle inflammation in myositis, new molecular pathways for targeted therapy have been discovered. Current therapies aim at different components of the innate or the adaptive immune response. Additionally, non-inflammatory mechanisms in myositis have come into focus as possible treatment targets. The use of therapeutical antibodies in myositis has been examined in various clinical studies, several of them randomized controlled ones: Depletion of B-cells by rituximab has been established as treatment of refractory myositis. IVIG, an antibody therapy in the wider sense, has now been licensed for DM following a recent positive clinical trial. Negative study results were reported in randomized trials with infliximab, sifalimumab and bimagrumab. Studies on basiliximab and eculizumab are currently underway, and are expected to yield results in a couple of years. Despite some promising results of clinical studies with antibody therapy in myositis, further research is crucial to optimize the treatment for this debilitating disease and to find treatment alternatives for treatment-refractory patients.