Benefit-Risk Profile of Sphingosine-1-Phosphate Receptor Modulators in Relapsing and Secondary Progressive Multiple Sclerosis.
Benefit-Risk Profile of Sphingosine-1-Phosphate Receptor Modulators in Relapsing and Secondary Progressive Multiple Sclerosis.
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DOI：
10.1007/s40265-017-0814-1
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发表时间：
2017-10
期刊：
影响因子：
11.5
通讯作者：
Wiendl H
中科院分区：
文献类型：
--
作者：
Comi G;Hartung HP;Bakshi R;Williams IM;Wiendl H
自fingolimod获批以来，几种选择性鞘氨醇-1-磷酸受体调节剂已进入多发性硬化症的临床开发。然而，鞘氨醇-1-磷酸受体调节剂可能出现副作用。通过考虑整个药物类别的短期数据和长期芬戈莫德数据，我们的目标是强调鞘氨醇-1-磷酸受体调节剂在多发性硬化症中的潜力，同时保证它们的获益-风险特征适合长期治疗。短期芬戈莫德研究证明了这类药物的有效性，表明首次给药时心脏事件是短暂的和可控的，并且表明严重的不良事件很少发生。选择性鞘氨醇-1-磷酸受体调节剂的早期研究也显示出类似或更高的安全性，并且剂量滴定降低了治疗开始效应。长期的芬戈莫德研究证明了持续的疗效，没有引起新的安全性问题，没有增加黄斑水肿、感染或恶性肿瘤的发生率。切换研究发现，从注射治疗切换到无洗脱期时，没有安全性问题，患者满意度和对芬戈莫德的坚持度更高。切换natalizumab时，短期洗脱期优于长期洗脱期。鞘氨醇-1-磷酸受体调节剂的特异性免疫调节作用与观察到的芬戈莫德长期药物相关不良反应的低发生率一致。选择性鞘氨醇-1-磷酸受体调节剂的短期数据支持其在多发性硬化症中的潜在有效性，改善的副作用可能会扩大患者对这类药物的使用。芬戈莫德的长期安全性、耐受性和持久性应该让临床医生放心，鞘氨醇-1-磷酸受体调节剂可能适用于多发性硬化症的长期治疗。本文的在线版本（doi:10.1007/s40265-017-0814-1）包含补充材料，仅供授权用户使用。
Since the approval of fingolimod, several selective sphingosine-1-phosphate receptor modulators have entered clinical development for multiple sclerosis. However, side effects can occur with sphingosine-1-phosphate receptor modulators. By considering short-term data across the drug class and longer term fingolimod data, we aim to highlight the potential of sphingosine-1-phosphate receptor modulators in multiple sclerosis, while offering reassurance that their benefit–risk profiles are suitable for long-term therapy. Short-term fingolimod studies demonstrated the efficacy of this drug class, showed that cardiac events upon first-dose administration are transient and manageable, and showed that serious adverse events are rare. Early-phase studies of selective sphingosine-1-phosphate receptor modulators also show efficacy with a similar or improved safety profile, and treatment initiation effects were reduced with dose titration. Longer term fingolimod studies demonstrated sustained efficacy and raised no new safety concerns, with no increases in macular edema, infection, or malignancy rates. Switch studies identified no safety concerns and greater patient satisfaction and persistence with fingolimod when switching from injectable therapies with no washout period. Better outcomes were seen with short than with long washouts when switching from natalizumab. The specific immunomodulatory effects of sphingosine-1-phosphate receptor modulators are consistent with the low observed rates of long-term, drug-related adverse effects with fingolimod. Short-term data for selective sphingosine-1-phosphate receptor modulators support their potential effectiveness in multiple sclerosis, and improved side-effect profiles may widen patient access to this drug class. The long-term safety, tolerability, and persistence profiles of fingolimod should reassure clinicians that sphingosine-1-phosphate receptor modulators are likely to be suitable for the long-term treatment of multiple sclerosis. The online version of this article (doi:10.1007/s40265-017-0814-1) contains supplementary material, which is available to authorized users.
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影响因子：
5.8
作者：
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通讯作者：
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DOI：
10.12703/p6-109
发表时间：
2014
期刊：
F1000prime reports
影响因子：
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作者：
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影响因子：
158.5
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Cohen, Jeffrey A.;Barkhof, Frederik;Kappos, Ludwig
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