It is challenging to select only a handful of papers, from the many published in different research areas in neuromuscular disorders, to highlight the most important advances in 2019. The focus here is on novel treatments and advances in our understanding of pathophysiology. For example, in 2019, the first randomised, placebo-controlled study of efgartigimod, an antagonist of the neonatal Fc receptor (FcRn), was done in patients with myasthenia gravis. FcRn inhibitors block the recycling of immunoglobulins, reducing levels of circulating pathogenic antibody by about 70%. In this randomised, placebo-controlled phase 2 trial, 24 patients with generalised myasthenia gravis and acetylcholine receptor antibodies were given intravenous efgartigimod (10 mg/kg) or placebo infusions four times in 3 weeks. The results of this study showed that intravenous efgartigimod was safe, well tolerated, and effective. Nine (75%) of 12 patients treated with efgartigimod significantly improved on four efficacy scales (the quantitative myasthenia gravis score, Myasthenia Gravis-specific Activities of Daily Living scale, myasthenia gravis composite scale, and Myasthenia Gravis Quality of Life scale) as early as 7 days after the first infusion, and improved maximally 1–2 weeks after the final infusion. Reductions on these four scales were observed in most patients (about three-quarters improved substantially), although one patient dropped out at day 36 because of low efficacy and worsening of myasthenia gravis. Following the success of this study, a phase 3 trial is underway in Europe, North America, and Japan ( ). Thus, FcRn inhibitors could become effective alternatives to immunoglobulin infusions, and might be used in conjunction with terminal complement inhibitors such as eculizumab or zilucoplan, which block the formation of the membrane attack complex. Addressing two different points in the aberrant immune activity is likely to improve clinical outcomes through a synergistic effect.

中文翻译：

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2019年神经肌肉研究的重要进展。

从神经肌肉疾病的不同研究领域中发表的众多论文中，仅选择几篇论文来突出显示2019年最重要的进展具有挑战性。本文的重点是新颖的治疗方法和我们对病理生理学的理解的进展。例如，在2019年，对重症肌无力患者进行了efgartigimod（一种新生儿Fc受体（FcRn）的拮抗剂）的首次随机，安慰剂对照研究。FcRn抑制剂可阻止免疫球蛋白的再循环，从而使循环中的病原性抗体水平降低约70％。在这项随机，安慰剂对照的2期试验中，对24例重症肌无力和乙酰胆碱受体抗体的患者在3周内进行了四次静脉注射efgartigimod（10 mg / kg）或安慰剂输注。这项研究的结果表明，静脉注射efgartigimod是安全，耐受性良好且有效的。最早在四种功效量表（重症肌无力定量评分，重症肌无力特异性日常生活活动量表，重症肌无力综合量表和重症肌无力生活质量量表）的四个功效量表上，有12名患者中有九名（75％）显着改善。第一次输注后7天，最后一次输注后最多可改善1-2周。在大多数患者中，这四个量表均有降低（大约四分之三的改善），尽管一名患者由于疗效差和重症肌无力恶化而在第36天退学。随着这项研究的成功，在欧洲，北美和日本（）正在进行3期试验。因此，FcRn抑制剂可成为免疫球蛋白输注的有效替代方法，并可与末端补体抑制剂（如依库丽单抗或zilucoplan）结合使用，后者可阻止膜攻击复合物的形成。解决异常的免疫活性中的两个不同点可能会通过协同效应改善临床结果。