Mellen Center, Cleveland Clinic, Cleveland, OH 44195, USA.
N Engl J Med. 2010 Feb 4;362(5):402-15. doi: 10.1056/NEJMoa0907839. Epub 2010 Jan 20.
BACKGROUND: Fingolimod (FTY720), a sphingosine-1-phosphate-receptor modulator that prevents lymphocyte egress from lymph nodes, showed clinical efficacy and improvement on imaging in a phase 2 study involving patients with multiple sclerosis. METHODS: In this 12-month, double-blind, double-dummy study, we randomly assigned 1292 patients with relapsing-remitting multiple sclerosis who had a recent history of at least one relapse to receive either oral fingolimod at a daily dose of either 1.25 or 0.5 mg or intramuscular interferon beta-1a (an established therapy for multiple sclerosis) at a weekly dose of 30 microg. The primary end point was the annualized relapse rate. Key secondary end points were the number of new or enlarged lesions on T(2)-weighted magnetic resonance imaging (MRI) scans at 12 months and progression of disability that was sustained for at least 3 months. RESULTS: A total of 1153 patients (89%) completed the study. The annualized relapse rate was significantly lower in both groups receiving fingolimod--0.20 (95% confidence interval [CI], 0.16 to 0.26) in the 1.25-mg group and 0.16 (95% CI, 0.12 to 0.21) in the 0.5-mg group--than in the interferon group (0.33; 95% CI, 0.26 to 0.42; P<0.001 for both comparisons). MRI findings supported the primary results. No significant differences were seen among the study groups with respect to progression of disability. Two fatal infections occurred in the group that received the 1.25-mg dose of fingolimod: disseminated primary varicella zoster and herpes simplex encephalitis. Other adverse events among patients receiving fingolimod were nonfatal herpesvirus infections, bradycardia and atrioventricular block, hypertension, macular edema, skin cancer, and elevated liver-enzyme levels. CONCLUSIONS: This trial showed the superior efficacy of oral fingolimod with respect to relapse rates and MRI outcomes in patients with multiple sclerosis, as compared with intramuscular interferon beta-1a. Longer studies are needed to assess the safety and efficacy of treatment beyond 1 year. (ClinicalTrials.gov number, NCT00340834.)
背景：芬戈莫德（FTY720）是一种鞘氨醇-1-磷酸受体调节剂，可阻止淋巴细胞从淋巴结迁出，在一项涉及多发性硬化症患者的 2 期研究中显示出临床疗效和影像学改善。
方法：在这项为期 12 个月的、双盲、双模拟研究中，我们随机分配了 1292 名近期至少有一次复发的复发缓解型多发性硬化症患者，分别接受每日 1.25 或 0.5mg 口服芬戈莫德或每周 30μg 肌肉注射干扰素β-1a（多发性硬化症的既定疗法）治疗。主要终点是年化复发率。关键次要终点是 12 个月时 T2 加权磁共振成像（MRI）扫描上新或扩大病变的数量以及持续至少 3 个月的残疾进展。
结果：共有 1153 名患者（89%）完成了研究。接受芬戈莫德治疗的两组患者的年化复发率均显著降低——1.25mg 组为 0.20（95%置信区间[CI]，0.16 至 0.26），0.5mg 组为 0.16（95%CI，0.12 至 0.21）——低于干扰素组（0.33；95%CI，0.26 至 0.42；两组比较均 P<0.001）。MRI 结果支持主要结果。残疾进展方面，各组之间无显著差异。接受 1.25mg 剂量芬戈莫德治疗的患者中发生了两例致命感染：播散性原发性带状疱疹和单纯疱疹脑炎。接受芬戈莫德治疗的患者还发生了其他不良事件，包括非致命性疱疹病毒感染、心动过缓和房室传导阻滞、高血压、黄斑水肿、皮肤癌和肝酶水平升高。
结论：与肌肉注射干扰素β-1a 相比，本试验显示口服芬戈莫德在多发性硬化症患者的复发率和 MRI 结果方面具有更好的疗效。需要更长时间的研究来评估 1 年以上治疗的安全性和疗效。（临床试验.gov 编号，NCT00340834。）
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