Thymectomy in non-thymomatous MG patients on Prednisone

描述(申请人提供)：重症肌无力(MG)是一种累及胸腺的自身免疫性疾病，85%的患者具有肌肉乙酰胆碱受体(AchR-Ab)抗体，该抗体干扰神经肌肉传递，可导致严重的、有时危及生命的虚弱。胸腺切除术已经在世界范围内用于治疗非胸腺瘤性MG，这是基于回顾性的非随机研究。泼尼松(一种皮质类固醇)也经常用于治疗MG。这两种疗法经常一起使用，而且都有不良影响。目前尚不清楚胸腺切除是否对同时接受强的松治疗的患者有益。为了在比较疗效的同时考察安全性，我们提出了一项多中心、多种族、国际、单盲、为期3年的临床试验。在该试验中，年龄18-60岁的非胸腺瘤性MG患者被随机分为扩大胸腺切除术(ETTX)和非胸腺切除术(非胸腺切除术)。这两组患者都将接受泼尼松治疗，由盲人评估师按照相同的方案进行治疗，目的是确定达到和维持最小表现状态所需的最小剂量。主要终点将包括反应和毒性，使用综合测量临床病程、短期和长期毒性的基础上：(A)通过QMG虚弱评分评估治疗的临床疗效(B)严重不良事件的频率(C)泼尼松的总剂量(剂量时间曲线下的面积，AUDTC)。有利于ETTX的显著差异将确立其在这一患者群体中的临床益处，并提供ETTX在未接受泼尼松药物治疗的患者中可能受益的间接证据。相反，如果不能证明主要终点的整体或个体成分存在显著差异，则表明胸腺切除术在研究人群中是不必要的。分组分析可以显示福利是否仅限于那些在进入时或在特定年龄组中使用强的松幼稚的人。因此，这一结果将对当前的临床实践产生影响。

DESCRIPTION (provided by applicant): Myasthenia gravis (MG) is an autoimmune disease involving the thymus in which 85% of patients have antibodies to muscle acetylcholine receptors (AchR-Ab) that interfere with neuromuscular transmission and can cause severe, sometimes life-threatening, weakness. Thymectomy has been used world-wide to treat non-thymomatous MG, based on retrospective non-randomized studies. Prednisone (a corticosteroid) is also frequently used to treat MG. Both therapies are often employed together and both have adverse effects. Whether thymectomy benefits those who are also receiving prednisone is not known. To investigate the safety while comparing efficacy, we propose a multicenter, multiracial, international, single-blinded, 3-year duration clinical trial in which patients aged 18-60 years with generalized AchR-Ab positive non- thymomatous MG are randomized to receive extended transsternal thymectomy (ETTX) or no thymectomy. Both groups will receive prednisone administered by a 'blind' evaluator according to the same set protocol aimed at establishing the minimum dose needed to achieve and maintain Minimal Manifestation (MM) status. The primary endpoint will comprise response and toxicity using a composite measuring clinical course, short and long term toxicities based on: (a) clinical efficacy of therapy evaluated by the QMG weakness score (b) frequency of serious adverse events (c) the total dose of prednisone (Area under the Dose time Curve, AUDTC). A significant difference favoring ETTX would establish its clinical benefits in this patient population, and provide indirect evidence of the possible benefits of ETTX in patients not receiving prednisone medication. Conversely, failure to demonstrate a significant difference in the global or individual components of the primary endpoint would suggest that thymectomy is an unnecessary procedure in the population studied. Subgroup analysis may show whether benefits are confined to those who are prednisone naive at entry or in a particular age group. Thus the results will impact on current clinical practice.