Di Li, Shen Faxiu, Wen Xinmei, Lu Yan, Zhu Wenjia, Wang Min, Da Yuwei
Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Department of Neurology, Beijing Pinggu Hospital, Beijing, China.
Front Immunol. 2022 Mar 18;13:839075. doi: 10.3389/fimmu.2022.839075. eCollection 2022.
Two clinical trials assessing the steroid-sparing effect of methotrexate (MTX) yielded conflicting results. Our objective was to investigate whether MTX would show a steroid-sparing effect in the treatment of generalized myasthenia gravis (MG) patients who fitted Myasthenia Gravis Foundation of America (MGFA) Class II and Class III.
We performed an 18-month prospective, randomized, open-labeled trial of prednisone combined with MTX 10 mg orally every week versus prednisone alone in 40 recently diagnosed MG patients of MGFA Class II and Class III between July 2014 and July 2018. The primary endpoint was the prednisone area under the dose-time curve (AUDTC) from months 3 to 18. Secondary endpoints included changes of the Quantitative Myasthenia Gravis Score (QMG), the Myasthenia Gravis Activity of Daily Living Score (MG-ADL), initial time of prednisone reduction, the median prednisone daily dose in each month, adverse events, and treatment failures in each group.
Forty participants were included; among those, 5 individuals withdrew. A total of 35 participants completed 18 months of follow-up (18 in prednisone+MTX, 17 in prednisone group). Combined use of MTX reduced the month 3-18 prednisone AUDTC (prednisone+MTX 5,663.44 ± 1,678.08 mg, prednisone 6,683.94 ± 678.08 mg, = 0.03, 95% confidence interval -1916.01 to -124.98). The initial times of prednisone reduction were 4.34 ± 1.44 months in the prednisone+MTX group and 5.56 ± 2.05 months in the prednisone group ( = 0.04, 95% CI -2.41 to -0.03). The median daily prednisone dose was significantly lower in the prednisone+MTX group at month 6 and months 9-18. No significant differences were found in QMG and MG-ADL scores between the two groups. No serious drug-related adverse events were observed in both groups.
This study provides evidence that MTX has the steroid-sparing ability in generalized MG patients of MGFA Class II and Class III.
http://www.chictr.org.cn/showproj.aspx?proj=10563 identifier ChiCTR-IPR-15006081.
两项评估甲氨蝶呤（MTX）激素节省作用的临床试验结果相互矛盾。我们的目的是研究MTX在治疗符合美国重症肌无力基金会（MGFA）II类和III类标准的全身型重症肌无力（MG）患者时是否具有激素节省作用。
2014年7月至2018年7月期间，我们对40例新诊断的MGFA II类和III类MG患者进行了一项为期18个月的前瞻性、随机、开放标签试验，比较泼尼松联合每周口服10mg MTX与单用泼尼松的疗效。主要终点是第3至18个月泼尼松的剂量-时间曲线下面积（AUDTC）。次要终点包括重症肌无力定量评分（QMG）、重症肌无力日常生活活动评分（MG-ADL）的变化、泼尼松减量的初始时间、每月泼尼松的日均剂量中位数、不良事件以及每组的治疗失败情况。
共纳入40名参与者，其中5人退出。共有35名参与者完成了18个月的随访（泼尼松+MTX组18人，泼尼松组17人）。联合使用MTX降低了第3至18个月泼尼松的AUDTC（泼尼松+MTX组为5663.44±1678.08mg，泼尼松组为6683.94±678.08mg，P=0.03，95%置信区间为-1916.01至-124.98）。泼尼松+MTX组泼尼松减量的初始时间为4.34±1.44个月，泼尼松组为5.56±2.05个月（P=0.04，95%CI为-2.41至-0.03）。在第6个月以及第9至18个月，泼尼松+MTX组的泼尼松日均剂量中位数显著更低。两组的QMG和MG-ADL评分无显著差异。两组均未观察到严重的药物相关不良事件。
本研究提供了证据表明MTX在MGFA II类和III类全身型MG患者中具有激素节省能力。
http://www.chictr.org.cn/showproj.aspx?proj=10563，标识符ChiCTR-IPR-15006081 。
