Spotlight on siponimod and its potential in the treatment of secondary progressive multiple sclerosis: the evidence to date.
Spotlight on siponimod and its potential in the treatment of secondary progressive multiple sclerosis: the evidence to date.
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DOI：
10.2147/dddt.s122249
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Gajofatto A
中科院分区：
文献类型：
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作者：
Gajofatto A
Siponimod(BAF312)是神经鞘氨醇-1-磷酸(S1P)调节剂家族的一种合成分子，具有神经保护作用，其免疫调节作用是通过隔离次级淋巴器官中的B细胞和T细胞来实现的。与Fingolimod(即商业上可用于治疗复发-缓解[RR]多发性硬化症[MS]的S1P调节剂的前体)相比，siponimod对1型和5型S1P受体具有选择性亲和力，导致主要由S1P3受体激活引起的不良事件的风险较低，如心动过缓和血管收缩。此外，S1P1和S1P5受体由神经元和神经胶质细胞表达，并可能介导药物的神经保护作用。西波利莫特治疗RR MS的II期临床试验显示，与安慰剂相比，该活性药物在治疗3个月后在减少脑磁共振成像(MRI)上的Gd增强病变方面具有显著效果。在最近完成的一项第三阶段试验中，与安慰剂相比，西波利莫特治疗与继发性进展性多发性硬化症(SP)患者的残疾进展显著减少有关。本文就目前支持西波利莫治疗SP-MS疗效的证据进行综述。
Siponimod (BAF312) is a synthetic molecule belonging to the sphingosine-1-phosphate (S1P) modulator family, which has putative neuroprotective properties and well-characterized immunomodulating effects mediated by sequestration of B and T cells in secondary lymphoid organs. Compared to fingolimod (ie, precursor of the S1P modulators commercially available for the treatment of relapsing–remitting [RR] multiple sclerosis [MS]), siponimod exhibits selective affinity for types 1 and 5 S1P receptor, leading to a lower risk of adverse events that are mainly induced by S1P3 receptor activation, such as bradycardia and vasoconstriction. In addition, S1P1 and S1P5 receptors are expressed by neurons and glia and could mediate a possible neuroprotective effect of the drug. A Phase II clinical trial of siponimod for RR MS showed a significant effect of the active drug compared to placebo on reducing gadolinium-enhancing lesions on brain magnetic resonance imaging (MRI) after 3 months of treatment. In a recently completed Phase III trial, treatment with siponimod was associated with a significant reduction in disability progression in secondary progressive (SP) MS patients compared to placebo. In this article, current evidence supporting siponimod efficacy for SP MS is reviewed.