Sifalimumab(Bristol Myers Squibb Co.)

As treatment of refractory idiopathic inflammatory myopathies (IIM) has been challenging, there is growing interest in assessing new therapies that target various pathways implicated in the pathogenesis of IIM. In the largest clinical trial to date, rituximab was studied in adult and juvenile myositis, but the primary outcome was not met despite 83 percent of subjects with refractory myositis meeting the definition of improvement. The U.S. Food and Drug Administration (FDA) has recently granted approval to Octagam 10% immune globulin intravenous (IVIg), for the treatment of adult dermatomyositis based on impressive results from a double-blind placebo-controlled trial. Anti-tumor necrosis factor (anti-TNF) utility in IIM is not recommended and recent reports suggest this therapy may induce systemic autoimmune disease including myositis. Further, anti-IL6 therapy cannot be recommended as a recent trial of tocilizumab failed to reach its primary endpoint. Further studies are needed to assess the role of newer therapies such as abatacept (inhibition of T cell co-stimulation), sifalimumab (anti-IFNα), Janus kinase [JAK] inhibitors, apremilast (phosphodiesterase 4 inhibitor), and KZR-616 (selective inhibitor of the immunoproteasome) given their biological plausibility and encouraging recent small-case series results. The future of IIM therapy will depend on exploring biomarkers implicated in the etiopathogenesis of IIM, improvements in myositis classification based on serological and histopathological features, and well-designed controlled clinical trials using validated consensus outcome measures.

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.