Yoshii Fumihito, Moriya Yusuke, Ohnuki Tomohide, Ryo Masafuchi, Takahashi Wakoh
Department of Neurology Saiseikai Hiratsuka Hospital Hiratsuka Japan.
Department of Neurology Tokai University Oiso Hospital Oiso Japan.
Clin Exp Neuroimmunol. 2017 Aug;8(3):233-243. doi: 10.1111/cen3.12397. Epub 2017 Jun 18.
Fingolimod (FTY) is the first oral medication approved for treatment of relapsing-remitting multiple sclerosis (RRMS). Its effectiveness and safety were confirmed in several phase III clinical trials, but proper evaluation of safety in the real patient population requires long-term post-marketing monitoring. Since the approval of FTY for RRMS in Japan in 2011, it has been administered to approximately 5000 MS patients, and there have been side-effect reports from 1750 patients. Major events included infectious diseases, hepatobiliary disorders, nervous system disorders and cardiac disorders. In the present review, we focus especially on central nervous system adverse events. The topics covered are: (i) clinical utility of FTY; (ii) safety profile; (iii) post-marketing adverse events in Japan; (iv) white matter (tumefactive) lesions; (v) rebound after FTY withdrawal; (vi) relationship between FTY and progressive multifocal leukoencephalopathy; (vii) FTY and progressive multifocal leukoencephalopathy-related immune reconstitution inflammatory syndrome; and (viii) neuromyelitis optica and leukoencephalopathy.
芬戈莫德（FTY）是首个被批准用于治疗复发缓解型多发性硬化症（RRMS）的口服药物。其有效性和安全性在多项III期临床试验中得到了证实，但要对真实患者群体的安全性进行恰当评估，需要长期的上市后监测。自2011年芬戈莫德在日本被批准用于RRMS治疗以来，已有约5000名MS患者使用过该药，其中1750名患者有副作用报告。主要事件包括感染性疾病、肝胆疾病、神经系统疾病和心脏疾病。在本综述中，我们特别关注中枢神经系统不良事件。涵盖的主题有：（i）芬戈莫德的临床效用；（ii）安全性概况；（iii）日本的上市后不良事件；（iv）白质（瘤样）病变；（v）芬戈莫德停药后的反弹；（vi）芬戈莫德与进行性多灶性白质脑病的关系；（vii）芬戈莫德与进行性多灶性白质脑病相关的免疫重建炎症综合征；以及（viii）视神经脊髓炎和白质脑病。
