Treatment of Immune-Mediated Necrotizing Myopathy.

Purpose of review: Immune-mediated necrotizing myositis (IMNM) is a rare autoimmune disorder characterized by proximal muscle weakness, elevated creatine kinase levels, and necrosis of muscle fibers. While the exact pathogenesis of IMNM remains unknown, anti-HMGCR and anti-SRP autoantibodies are associated with different predisposing factors, clinical manifestations, and severity of the disease and are believed to correspond to two pathogenically distinct entities. The cornerstone treatment for IMNM is a combination of glucocorticoids and steroid-sparing agents. Therapeutic strategies aimed at decreasing the half-life of endogenous autoantibodies, such as intravenous immunoglobulin (IVIG), or reducing their production, such as rituximab, have shown promise as powerful treatments. In severe cases, combining IVIG and rituximab can have synergistic effects.

Recent findings: Previous studies suggested that complement dysregulation may be involved in the pathogenesis of IMNM. However, a recent phase 2 clinical trial evaluating the effectiveness of zilucoplan, a C5 inhibitor, failed to show efficacy in IMNM.

Summary: In this review, we aim to provide a comprehensive review of IMNM focusing on the current evidence regarding treatment options for this condition. Our goal is to present an up-to-date overview of the current state of therapeutics on IMNM and highlight potential areas for future investigation.