Thymectomy in Non-Thymomatous MG Patients on Prednisone

重症肌无力（MG）是一种累及胸腺的自身免疫性疾病，85%的患者有肌乙酰胆碱受体（AchR-Ab）抗体，该抗体干扰神经肌肉传递，可导致严重的，有时危及生命的无力。基于回顾性非随机研究，胸腺切除术已在世界范围内用于治疗非胸腺瘤性MG。强的松（一种皮质类固醇）也常用于治疗MG。这两种疗法经常同时使用，而且都有副作用。胸腺切除术是否对同时接受强的松治疗的患者有益尚不清楚。为了在比较疗效的同时研究安全性，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，18-60岁的广泛性AchR-Ab阳性非胸腺瘤性MG患者随机接受延长经胸骨胸腺切除术（ETTX）或不接受胸腺切除术。两组患者均接受强的松治疗，由“盲”评估者根据相同的方案给药，旨在确定达到和维持最小表现（MM）状态所需的最小剂量。主要终点将包括反应和毒性，使用综合测量临床过程，短期和长期毒性，基于：(a) QMG弱点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（剂量时间曲线下面积，AUDTC）。支持ETTX的显著差异将确定其在该患者群体中的临床益处，并为未接受强的松治疗的患者提供ETTX可能获益的间接证据。相反，如果不能证明主要终点的整体或个体成分有显著差异，则表明胸腺切除术在研究人群中是不必要的手术。亚组分析可以显示益处是否局限于入组时未使用强的松的患者或特定年龄组的患者。因此，研究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.