Antibody Therapies in Autoimmune Inflammatory Myopathies: Promising Treatment Options

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.

Keywords: Antibodies; Clinical trial; Inflammatory myopathies; Myositis; Rituximab; Treatment.

Fig. 1

Overview of antibody therapies tested in myositis. The figure provides an overview of antibody therapies that have been tested for efficacy and tolerability in myositis to date. The left panel includes antibody therapies that have been tested in polymyositis (PM), dermatomyositis (DM), juvenile dermatomyositis (JDM), necrotizing myopathy (NM), overlap myositis (OM) and antisynthetase syndrome (ASS). The right panel shows antibody therapies that have been tested in inclusion body myositis (IBM). The colours illustrate the study outcomes: Green-framed study drugs have shown improvement in clinical trials, red-framed study drugs achieved no improvement in clinical trials and grey-framed study drugs achieved some improvements, but did not reach statistical significance. Solid lines display randomized, double-blind and placebo-controlled clinical trials. Dashed lines point out open-label trials, and dotted lines indicate case series and case reports. Several antibody therapies have been examined in randomized, double-blind and placebo-controlled clinical trials. For basiliximab and eculizumab, only case series or case reports are available so far. Several trials have shown beneficial treatment effects in myositis (green)