Therapeutic Management of Immune-Mediated Necrotizing Myositis

Abstract

The idiopathic inflammatory myopathies are a heterogeneous group of autoimmune disorders characterized by skeletal muscle inflammation leading to chronic muscle weakness. Immune-mediated necrotizing myopathy (IMNM) is a distinct subgroup of inflammatory myopathy typically characterized by myofiber necrosis with minimal inflammatory infiltrates on muscle biopsy, highly elevated creatine kinase levels, and infrequent extra-muscular involvement. This review provides an overview of currently recommended treatment strategies for IMNM, including discussion of disease activity monitoring and recommended first-line immunomodulatory agents depending on clinical phenotype and autoantibody status. IMNM can be divided into three subtypes based on autoantibody positivity: anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) IMNM, anti-signal recognition particle (SRP) IMNM, and antibody-negative IMNM. Autoantibody status in IMNM has considerable correlation with clinical phenotype, prognosis, and recommended choice of immunosuppressive agent. Patients with anti-HMGCR IMNM tend to respond well to intravenous immunoglobulin (IVIG), and IVIG monotherapy may be a sufficient treatment for certain patients. In anti-SRP IMNM, early rituximab is commonly favored. More generally, prompt initiation of aggressive immunosuppression is often indicated, as both anti-SRP and anti-HMGCR IMNM can potentially cause debilitating weakness, muscle atrophy and irreversible fatty replacement happen early in the disease course. Patients with IMNM frequently require combination therapy to achieve disease control and have a high rate of relapse when tapering immunosuppression. Young age of onset is a poor prognostic factor. IMNM can be severely disabling and often requires aggressive immunosuppression. For any given patient, the treatment strategy should be informed by the severity of their presenting features and autoantibody status. While our ability to treat IMNM has certainly improved, there remains a need for more prospective trials to inform optimal treatment strategies.