Ogbonnaya-Whittlesey Sandra Amara, Kobrin Dale, Casal-Dominguez Maria, Mammen Andrew L, Pinal-Fernandez Iago
Muscle Disease Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, 50 South Drive, Room 1141, Building 50, MSC 8024, Bethesda, MD 20892, USA.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Curr Treatm Opt Rheumatol. 2023 Dec;9(4):168-178. doi: 10.1007/s40674-023-00210-2. Epub 2023 Jul 13.
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.
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.
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.
免疫介导性坏死性肌炎（IMNM）是一种罕见的自身免疫性疾病，其特征为近端肌无力、肌酸激酶水平升高以及肌纤维坏死。虽然IMNM的确切发病机制尚不清楚，但抗HMGCR和抗SRP自身抗体与不同的易感因素、临床表现及疾病严重程度相关，且被认为对应两种致病机制不同的实体。IMNM的基础治疗是糖皮质激素与激素节约剂联合使用。旨在缩短内源性自身抗体半衰期的治疗策略，如静脉注射免疫球蛋白（IVIG），或减少其产生的策略，如利妥昔单抗，已显示出有望成为有效的治疗方法。在严重病例中，联合使用IVIG和利妥昔单抗可产生协同效应。
既往研究提示补体失调可能参与IMNM的发病机制。然而，最近一项评估C5抑制剂zilucoplan疗效的2期临床试验未显示其对IMNM有效。
在本综述中，我们旨在全面回顾IMNM，重点关注有关该疾病治疗选择的现有证据。我们的目标是呈现IMNM治疗现状的最新概述，并突出未来研究的潜在领域。
