Fingolimod for multiple sclerosis and emerging indications: appropriate patient selection, safety precautions, and special considerations.
Fingolimod for multiple sclerosis and emerging indications: appropriate patient selection, safety precautions, and special considerations.
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DOI：
10.2147/tcrm.s65558
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发表时间：
2016
影响因子：
2.8
通讯作者：
Kleiter I
中科院分区：
文献类型：
--
作者：
Ayzenberg I;Hoepner R;Kleiter I
芬戈莫德（FTY 720）是一种靶向鞘氨醇-1-磷酸受体的免疫抑制药物，是一种广泛用于复发缓解型多发性硬化症（MS）的药物。除了关键的III期临床试验证明了每周一次对安慰剂和干扰素-β-1a的疗效外，现在有足够的临床数据来评估其真实世界的疗效和安全性。芬戈莫德的批准适应症因国家而异。这种差异在一定程度上反映了芬戈莫德在不断扩大的多发性硬化症药物阵容中的中间地位。随着治疗的个体化，适当的患者选择变得更加重要。我们讨论了芬戈莫德用于复发缓解型MS的各种情况及其陷阱：作为一线治疗，作为既往免疫治疗失败后的升级治疗，以及作为高效免疫治疗后的降级治疗。潜在的副作用，如心动过缓，感染，黄斑水肿，致畸性，进行性多灶性白质脑病以及适当的安全预防措施进行了概述。已经描述了芬戈莫德停药后疾病再激活;因此，应在芬戈莫德停药后数月内密切监测患者的MS活动。最后，我们讨论了临床前和临床数据表明芬戈莫德的神经保护作用，这可能为未来的适应症，如中风，阿尔茨海默病和其他神经退行性疾病开辟道路。
Fingolimod (FTY720), an immunotherapeutic drug targeting the sphingosine-1-phosphate receptor, is a widely used medication for relapsing-remitting multiple sclerosis (MS). Apart from the pivotal Phase III trials demonstrating efficacy against placebo and interferon-β-1a once weekly, sufficient clinical data are now available to assess its real-world efficacy and safety profile. Approved indications of fingolimod differ between countries. This discrepancy, to some extent, reflects the intermediate position of fingolimod in the expanding lineup of MS medications. With individualization of therapy, appropriate patient selection gets more important. We discuss various scenarios for fingolimod use in relapsing-remitting MS and their pitfalls: as first-line therapy, as escalation therapy after failure of previous immunotherapies, and as de-escalation therapy following highly potent immunotherapies. Potential side effects such as bradycardia, infections, macular edema, teratogenicity, and progressive multifocal leukoencephalopathy as well as appropriate safety precautions are outlined. Disease reactivation has been described upon fingolimod cessation; therefore, patients should be closely monitored for MS activity for several months after stopping fingolimod. Finally, we discuss preclinical and clinical data indicating neuroprotective effects of fingolimod, which might open the way to future indications such as stroke, Alzheimer’s disease, and other neurodegenerative disorders.