Antozzi Carlo, Mantegazza Renato
Neuroimmunology and Neuromuscular Diseases Unit, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy.
Immunotherapy and Apheresis Departmental Unit, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy.
Patient Relat Outcome Meas. 2023 Oct 18;14:305-312. doi: 10.2147/PROM.S408175. eCollection 2023.
Myasthenia gravis (MG) is an autoimmune ion channel disorder in which antibodies to different end-plate antigens impair neuromuscular transmission, ultimately leading to muscle weakness and fatigability. In about 85% of patients with MG, autoantibodies against the acetylcholine receptor (AChR) activate the complement cascade, causing damage to the neuromuscular junction. MG is a chronic disorder for which standard therapies with corticosteroids, immunosuppressive drugs, and immunomodulation with plasma exchange or intravenous immunoglobulins modify the course of the disease, but the residual burden of physical, psychological, and social disability highlights several unmet needs, among these the need for specific, targeted, and well tolerated therapies able to improve the patients' quality of life. Complement inhibition paved the way to precision medicine in MG since, for the first time, a specific therapy targeting a crucial pathogenetic step has been designed, tested, and proven to be effective in a controlled fashion. Ravulizumab represents the first long-acting complement inhibitor approved for treatment of patients with generalized MG, able to provide rapid, complete, and sustained complement inhibition. Ravulizumab improved the MG Activity of Daily Living scale and other clinical parameters up to 26 weeks as shown by the CHAMPION MG trial, and by its open label extension, with the added value of being administered every 8 weeks. The schedule of administration is likely to improve patients' adherence and hence their quality of life. The introduction of complement inhibition will considerably change the traditional therapeutic strategy for MG.
重症肌无力(MG)是一种自身免疫性离子通道疾病,针对不同终板抗原的抗体损害神经肌肉传递,最终导致肌肉无力和易疲劳。在约85%的重症肌无力患者中,抗乙酰胆碱受体(AChR)自身抗体激活补体级联反应,对神经肌肉接头造成损害。重症肌无力是一种慢性疾病,使用皮质类固醇、免疫抑制药物以及通过血浆置换或静脉注射免疫球蛋白进行免疫调节的标准疗法可改变疾病进程,但身体、心理和社会残疾的残留负担凸显了一些未满足的需求,其中包括需要能够改善患者生活质量的特异性、靶向性且耐受性良好的疗法。补体抑制为重症肌无力的精准医学铺平了道路,因为首次设计、测试并以可控方式证明了一种针对关键致病步骤的特异性疗法是有效的。ravulizumab是首个被批准用于治疗全身型重症肌无力患者的长效补体抑制剂,能够提供快速、完全且持续的补体抑制作用。如CHAMPION MG试验及其开放标签扩展试验所示,ravulizumab在长达26周的时间里改善了重症肌无力日常生活活动量表及其他临床参数,其附加价值在于每8周给药一次。给药方案可能会提高患者的依从性,从而改善他们的生活质量。补体抑制的引入将极大地改变重症肌无力的传统治疗策略。