Tacrolimus in the treatment of myasthenia gravis in patients with an inadequate response to glucocorticoid therapy: randomized, double-blind, placebo-controlled study conducted in China
单位：[1]Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China[2]Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China院本部神经科神经科外科泌尿外科中山大学附属第一医院[3]Department of Neurology, Qilu Hospital of Shandong University, Shandong, China[4]Department of Neurology, The Affiliated Hospital of Medical College Qingdao University, Qingdao, China[5]Department of Neurology, West China Hospital, Sichuan University, Sichuan, China四川大学华西医院[6]Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, China[7]Department of Neurology, Tongji Hospital, Tongji Medical College of Huazhong University of Science & Technology, Wuhan, China华中科技大学同济医学院附属同济医院[8]Department of Neurology, The First Hospital of Jilin University, Changchun, China[9]Department of Neurology, The First Affiliated Hospital of Soochow University, Jiangsu, China[10]Department of Neurology, Beijing Friendship Hospital Affiliated to Capital University of Medical Sciences, Beijing, China临床科室神经内科神经内科首都医科大学附属北京友谊医院[11]Department of Neurology, Beijing Hospital, Beijing, China[12]Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China[13]Astellas Pharma China, Inc., Beijing, China
Background To determine the efficacy of low-dose, immediate-release tacrolimus in patients with myasthenia gravis (MG) with inadequate response to glucocorticoid therapy in a randomized, double-blind, placebo-controlled study. Methods Eligible patients had inadequate response to glucocorticoids (GCs) after 6 weeks of treatment with prednisone 0.75 mg/kg/day or 60-100 mg/day. Patients were randomized to receive 3 mg tacrolimus or placebo daily (orally) for 24 weeks. Concomitant glucocorticoids and pyridostigmine were allowed. Patients continued GC therapy from weeks 1-4; from week 5, the dose was decreased at the discretion of the investigator. The primary efficacy outcome measure was a reduction, relative to baseline, in quantitative myasthenia gravis (QMG) score assessed using a generalized linear model; supportive analyses used alternative models. ResultsOf 138 patients screened, 83 [tacrolimus (n = 45); placebo (n = 38)] were enrolled and treated. The change in adjusted mean QMG score from baseline to week 24 was -4.9 for tacrolimus and -3.3 for placebo (least squares mean difference: -1.7, 95% confidence interval: -3.5, -0.1; p = 0.067). A post-hoc analysis demonstrated a statistically significant difference for QMG score reduction of 4 points in the tacrolimus group (68.2%) versus the placebo group (44.7%; p = 0.044). Adverse event profiles were similar between treatment groups. Conclusions Tacrolimus 3 mg treatment for patients with MG and inadequate response to GCs did not demonstrate a statistically significant improvement in the primary endpoint versus placebo over 24 weeks; however, a post-hoc analysis demonstrated a statistically significant difference for QMG score reduction of 4 points in the tacrolimus group versus the placebo group. This study was limited by the low number of patients, the absence of testing for acetylcholine receptor antibody and the absence of stratification by disease duration (which led to a disparity between the two groups). ClinicalTrials.gov identifier: NCT01325571
第一作者单位：[1]Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China[*1]Department of Neurology, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Rd, Shanghai, 200040, China
推荐引用方式(GB/T 7714)：
Lei Zhou,Weibin Liu,Wei Li,et al.Tacrolimus in the treatment of myasthenia gravis in patients with an inadequate response to glucocorticoid therapy: randomized, double-blind, placebo-controlled study conducted in China[J].THERAPEUTIC ADVANCES in NEUROLOGICAL DISORDERS.2017,10(9):315-325.doi:10.1177/1756285617721092.
APA：
Lei Zhou,Weibin Liu,Wei Li,Haifeng Li,Xu Zhang...&Chongbo Zhao.(2017).Tacrolimus in the treatment of myasthenia gravis in patients with an inadequate response to glucocorticoid therapy: randomized, double-blind, placebo-controlled study conducted in China.THERAPEUTIC ADVANCES in NEUROLOGICAL DISORDERS,10,(9)
MLA：
Lei Zhou,et al."Tacrolimus in the treatment of myasthenia gravis in patients with an inadequate response to glucocorticoid therapy: randomized, double-blind, placebo-controlled study conducted in China".THERAPEUTIC ADVANCES in NEUROLOGICAL DISORDERS 10..9(2017):315-325
：