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继发进展型多发性硬化的疾病修正治疗

[Disease-modifying treatment of secondary progressive multiple sclerosis].

作者信息

Hoffmann Olaf, Gold Ralf

机构信息

NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Deutschland.

Klinik für Neurologie, Alexianer St. Josefs-Krankenhaus, 14471, Potsdam, Deutschland.

出版信息

Nervenarzt. 2021 Oct;92(10):1052-1060. doi: 10.1007/s00115-021-01080-6. Epub 2021 Mar 3.

DOI:10.1007/s00115-021-01080-6
PMID:33656569
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8484088/
Abstract

BACKGROUND

Multiple sclerosis (MS) is a disease continuum from a clinically isolated syndrome through relapsing remitting MS to secondary progressive MS (SPMS). There are numerous therapeutic approaches with proven efficacy on relapse and focal inflammatory disease aspects, whereas treatment of secondary progression and associated neuropathological aspects continues to be a challenge.

OBJECTIVE

Overview of the current options for disease-modifying treatment of SPMS.

MATERIAL AND METHODS

Results of randomized clinical trials are presented and evaluated on a substance-specific basis.

RESULTS

Randomized SPMS trials showed inconsistent results regarding disability progression for beta interferons and negative results for natalizumab. Oral cladribine and ocrelizumab reduced disability progression in relapsing MS but have not been specifically studied in an SPMS population. Positive results for mitoxantrone are only partially applicable to current SPMS patients. For siponimod, a substance that crosses the blood-brain barrier, the EXPAND trial demonstrated a significant reduction in the risk of disability progression in typical SPMS. Subgroup analyses suggest a higher efficacy of siponimod in younger patients with active SPMS.

CONCLUSION

There is limited evidence for the use of previously available disease-modifying treatment in SPMS. Siponimod represents a new therapeutic option for active SPMS, defined by relapses or focal inflammatory MRI activity. To establish the therapeutic indications for siponimod, early detection of relapse-independent progression as well as differentiation of active SPMS from inactive disease are of critical importance.

摘要

背景

多发性硬化症(MS)是一种疾病连续体,从临床孤立综合征到复发缓解型MS再到继发进展型MS(SPMS)。在复发和局灶性炎症性疾病方面有许多已证实有效的治疗方法,而继发进展及相关神经病理学方面的治疗仍然是一个挑战。

目的

概述目前SPMS疾病修饰治疗的选择。

材料与方法

在特定物质基础上展示并评估随机临床试验结果。

结果

关于β干扰素,随机SPMS试验显示残疾进展结果不一致,那他珠单抗试验结果为阴性。口服克拉屈滨和奥瑞珠单抗可减少复发型MS的残疾进展,但尚未在SPMS人群中进行专门研究。米托蒽醌的阳性结果仅部分适用于当前的SPMS患者。对于一种可穿过血脑屏障的物质西尼莫德,EXPAND试验表明典型SPMS患者残疾进展风险显著降低。亚组分析表明西尼莫德在年轻的活动性SPMS患者中疗效更高。

结论

在SPMS中使用先前可用的疾病修饰治疗的证据有限。西尼莫德是活动性SPMS(由复发或局灶性炎症性MRI活动定义)的一种新治疗选择。为确立西尼莫德的治疗适应证,早期发现与复发无关的进展以及区分活动性SPMS与非活动性疾病至关重要。

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引用本文的文献

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Front Neurol. 2024 Mar 11;15:1295770. doi: 10.3389/fneur.2024.1295770. eCollection 2024.

本文引用的文献

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Does Siponimod Exert Direct Effects in the Central Nervous System?西尼莫德是否在中枢神经系统中发挥直接作用?
Cells. 2020 Jul 24;9(8):1771. doi: 10.3390/cells9081771.
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Contribution of Relapse-Independent Progression vs Relapse-Associated Worsening to Overall Confirmed Disability Accumulation in Typical Relapsing Multiple Sclerosis in a Pooled Analysis of 2 Randomized Clinical Trials.在两项随机临床试验的汇总分析中,复发无关进展与复发相关恶化对典型复发型多发性硬化症总体确认残疾累积的贡献。
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Progressive multiple sclerosis: latest therapeutic developments and future directions.进展性多发性硬化症:最新治疗进展与未来方向
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The next-generation sphingosine-1 receptor modulator BAF312 (siponimod) improves cortical network functionality in focal autoimmune encephalomyelitis.下一代鞘氨醇-1受体调节剂BAF312(西尼莫德)可改善局灶性自身免疫性脑脊髓炎中的皮质网络功能。
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