Department of Neurology, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, USA.
Department of Neurology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Lancet Neurol. 2019 Mar;18(3):259-268. doi: 10.1016/S1474-4422(18)30392-2. Epub 2019 Jan 25.
The Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) showed that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status as measured by the Quantitative Myasthenia Gravis (QMG) score in patients with generalised non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events.
We did a rater-blinded 2-year extension study at 36 centres in 15 countries for all patients who completed the randomised controlled MGTX and were willing to participate. MGTX patients were aged 18 to 65 years at enrolment, had generalised non-thymomatous myasthenia gravis of less than 5 years' duration, had acetylcholine receptor antibody titres of 1·00 nmol/L or higher (or concentrations of 0·50-0·99 nmol/L if diagnosis was confirmed by positive edrophonium or abnormal repetitive nerve stimulation, or abnormal single fibre electromyography), had Myasthenia Gravis Foundation of America Clinical Classification Class II-IV disease, and were on optimal anticholinesterase therapy with or without oral corticosteroids. In MGTX, patients were randomly assigned (1:1) to either thymectomy plus prednisone or prednisone alone. All patients in both groups received oral prednisone at doses titrated up to 100 mg on alternate days until they achieved minimal manifestation status. The primary endpoints of the extension phase were the time-weighted means of the QMG score and alternate-day prednisone dose from month 0 to month 60. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00294658. It is closed to new participants, with follow-up completed.
Of the 111 patients who completed the 3-year MGTX, 68 (61%) entered the extension study between Sept 1, 2009, and Aug 26, 2015 (33 in the prednisone alone group and 35 in the prednisone plus thymectomy group). 50 (74%) patients completed the 60-month assessment, 24 in the prednisone alone group and 26 in the prednisone plus thymectomy group. At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted mean QMG scores (5·47 [SD 3·87] vs 9·34 [5·08]; p=0·0007) and mean alternate-day prednisone doses (24 mg [SD 21] vs 48 mg [29]; p=0·0002) than did those in the prednisone alone group. 14 (42%) of 33 patients in the prednisone group, and 12 (34%) of 35 in the thymectomy plus prednisone group, had at least one adverse event by month 60. No treatment-related deaths were reported during the extension phase.
At 5 years, thymectomy plus prednisone continues to confer benefits in patients with generalised non-thymomatous myasthenia gravis compared with prednisone alone. Although caution is appropriate when generalising our findings because of the small sample size of our study, they nevertheless provide further support for the benefits of thymectomy in patients with generalised non-thymomatous myasthenia gravis.
National Institutes of Health, National Institute of Neurological Disorders and Stroke.
在接受泼尼松治疗的非胸腺瘤重症肌无力患者胸腺切除术试验（MGTX）中，与单独使用泼尼松相比，胸腺切除术联合泼尼松在改善临床状态方面具有优势，这是通过在 3 年内对广泛性非胸腺瘤重症肌无力患者的定量重症肌无力（QMG）评分进行衡量的。我们研究了胸腺切除术在长达 5 年内对临床状态、药物需求和不良事件的长期影响。
我们在 15 个国家的 36 个中心进行了一项由评估者盲法的 2 年扩展研究，所有完成随机对照 MGTX 且愿意参与的患者均可参加。MGTX 患者在入组时年龄为 18 至 65 岁，患有病程少于 5 年的广泛性非胸腺瘤重症肌无力，乙酰胆碱受体抗体滴度为 1.00 nmol/L 或更高（如果诊断通过阳性依酚氯铵或异常重复神经刺激或异常单纤维肌电图证实，则为 0.50-0.99 nmol/L），具有美国重症肌无力基金会临床分类 II-IV 级疾病，并且接受最佳抗胆碱酯酶治疗，同时或不联合口服皮质类固醇。在 MGTX 中，患者被随机分配（1:1）接受胸腺切除术加泼尼松或单独使用泼尼松。两组患者均在口服泼尼松，剂量滴定至隔日 100mg，直至达到最小症状状态。扩展阶段的主要终点是从第 0 个月到第 60 个月时 QMG 评分和隔日泼尼松剂量的时间加权平均值。分析按意向治疗进行。该试验在 ClinicalTrials.gov 注册，编号为 NCT00294658。该试验对新参与者关闭，随访已完成。
在完成 3 年 MGTX 的 111 名患者中，有 68 名（61%）于 2009 年 9 月 1 日至 2015 年 8 月 26 日进入扩展研究（泼尼松组 33 名，泼尼松加胸腺切除术组 35 名）。50 名（74%）患者完成了 60 个月的评估，泼尼松组 24 名，泼尼松加胸腺切除术组 26 名。在 5 年时，与单独使用泼尼松组相比，胸腺切除术加泼尼松组患者的 QMG 评分时间加权平均值（5.47[3.87]比 9.34[5.08]；p=0.0007）和隔日泼尼松剂量的平均值（24mg[21]比 48mg[29]；p=0.0002）显著更低。泼尼松组 33 名患者中有 14 名（42%），胸腺切除术加泼尼松组 35 名患者中有 12 名（34%）在第 60 个月时有至少一次不良事件。在扩展阶段没有报告与治疗相关的死亡。
在 5 年时，与单独使用泼尼松相比，胸腺切除术加泼尼松继续为广泛性非胸腺瘤重症肌无力患者带来获益。尽管由于我们研究的样本量较小，因此对我们的发现进行概括时应谨慎，但它们仍然为胸腺切除术在广泛性非胸腺瘤重症肌无力患者中的益处提供了进一步的支持。
美国国立卫生研究院，美国国立神经病学与中风研究所。
