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.

Myopathies in Clinical Care: A Focus on Treatable Causes

“…There could be patients requiring steroids and in such a situation, it could be administered every other day together with the daily steroid-sparing agent. If the patient does not respond to these medications or experiences severe extramuscular symptoms, second-line agents such as cyclosporine and tacrolimus may be used [50].…”

“…In some settings, IVIG /subcutaneous gamma globulin, may also be applied. Cyclophosphamide, often in combination with other immunomodulatory agents like rituximab and IVIG, is reserved for severe cases or systemic organ involvement [50].…”

Myositis: von der Diagnose zur Therapie

“…Eine Reihe an klinischen Studien wird derzeit auf internationaler Ebene und auch mit deutscher Beteiligung durchgeführt zu praktisch allen Formen der Myositis. Es handelt sich um alle Stufen der Studien, von explorativ bis zur Zulassungsstudie [ 18 , 22 , 23 ].…”

Mitochondrial defects in sporadic inclusion body myositis—causes and consequences

“…They are often administrated with other immunosuppressants like azathioprine and methotrexate to reduce steroid-related side effects like osteoporosis and cardiovascular diseases ( Oddis, 2016 ). Second-line treatments such as cyclosporine, tacrolimus, and intravenous immunoglobin are used to alleviate the disease symptoms in refractory or severe PM and DM cases ( Zeng et al, 2022 ; Skolka and Naddaf, 2023 ). Nonetheless, these immunosuppressive agents are not enduringly effective in treating some IIM patients, particularly those with sIBM ( Skolka and Naddaf, 2023 ).…”