Department of Neurology and INSPE, Scientific Institute Hospital San Raffaele, Vita-Salute San Raffaele University, Milan, Italy.
Department of Neurology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
Drugs. 2017 Oct;77(16):1755-1768. doi: 10.1007/s40265-017-0814-1.
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.
自从芬戈莫德获得批准以来，已有几种选择性鞘氨醇-1-磷酸受体调节剂进入多发性硬化症的临床开发阶段。然而，鞘氨醇-1-磷酸受体调节剂会产生副作用。通过考虑该药物类别中的短期数据和更长期的芬戈莫德数据，我们旨在强调鞘氨醇-1-磷酸受体调节剂在多发性硬化症中的潜力，同时确保其获益-风险状况适合长期治疗。短期芬戈莫德研究证明了该药物类别的疗效，表明首次给药时的心脏事件是短暂且可管理的，并且严重不良事件很少见。选择性鞘氨醇-1-磷酸受体调节剂的早期研究也显示出疗效，安全性与类似或改善，并且通过剂量滴定降低了起始治疗效应。长期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，黄斑水肿、感染或恶性肿瘤发生率没有增加。转换研究没有发现安全性问题，并且在没有冲洗期的情况下从注射疗法转换为芬戈莫德时，患者的满意度和坚持率更高。与从那他珠单抗转换相比，冲洗时间较短时的结果更好。鞘氨醇-1-磷酸受体调节剂的特定免疫调节作用与芬戈莫德观察到的长期、与药物相关的不良事件发生率低相一致。选择性鞘氨醇-1-磷酸受体调节剂的短期数据支持它们在多发性硬化症中的潜在有效性，并且改善的副作用概况可能会扩大患者对该药物类别的使用。芬戈莫德的长期安全性、耐受性和持久性概况应使临床医生放心，鞘氨醇-1-磷酸受体调节剂可能适合多发性硬化症的长期治疗。
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