Lei Zhou1, Weibin Liu2, Wei Li3, Haifeng Li3, Xu Zhang6, Huifang Shang5, Xu Zhang6, Bitao Bu7, Hui Deng8, Qi Fang9, Jimei Li10, Hua Zhang11, Zhi Song12, Changyi Ou2, Chuanzhu Yan3, Tao Liu4, Hongyu Zhou5, Jianhong Bao6, Jiahong Lu1, Huawei Shi13, Chongbo Zhao14. 1. Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China. 2. Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. 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. 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. 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. 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. 14. Department of Neurology, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Rd, Shanghai, 200040, China.
Abstract
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 withprednisone ⩾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. RESULTS: Of 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.
RCT Entities:
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 mgtacrolimus 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. RESULTS: Of 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.
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