Therapeutic decisions in multiple sclerosis: moving beyond efficacy.
Therapeutic decisions in multiple sclerosis: moving beyond efficacy.
复制标题
DOI：
10.1001/jamaneurol.2013.3510
复制
发表时间：
2013-10
期刊：
影响因子：
29
通讯作者：
Zamvil, Scott S.
中科院分区：
文献类型：
--
作者：
Brueck, Wolfgang;Gold, Ralf;Lund, Brett T.;Oreja-Guevara, Celia;Prat, Alexandre;Spencer, Collin M.;Steinman, Lawrence;Tintore, Mar;Vollmer, Timothy L.;Weber, Martin S.;Weiner, Leslie P.;Ziemssen, Tjalf;Zamvil, Scott S.
几种用于复发缓解型多发性硬化症（RRMS）的创新疾病修饰治疗（DMT）最近已获得许可，或处于后期开发阶段。这些DMT中的几种的分子靶标是明确定义的。所有这些都会影响四种特性中的至少一种：（1）免疫细胞运输，（2）细胞消耗，（3）免疫细胞功能，或（4）细胞复制。与β-干扰素和醋酸格拉替雷（第一代DMT）相比，几种较新的疗法充满了安全性问题。除了疗效外，了解DMT的作用机制（MOA）与其安全性特征之间的关系对于患者护理决策至关重要。在这篇文章中，我们将新型DMT的安全性问题与其药理学特征联系起来，包括分子靶点、MOA、化学结构和代谢。一些较新的DMT也代表了对以前用于其他疾病的治疗方法的重新利用或修改。在这里，我们描述了如何识别和理解这些同类药物中观察到的不良事件（AE），提供有关新MS治疗药物安全性和毒性的线索。虽然对DMT毒性的潜在机制的理解还不完整，但重要的是进一步发展这一知识，以最大限度地降低患者的风险，并确保未来的治疗具有最有利的风险-获益特征。当考虑按顺序和可能的组合使用这些药物时，认识到这里描述的DMT的各个类别可能是有益的。
Several innovative disease-modifying treatments (DMTs) for relapsing remitting multiple sclerosis (RRMS) have been licensed recently, or are in late-stage development. The molecular targets of several of these DMTs are well defined. All affect at least one of four properties: (1) immune cell trafficking, (2) cell depletion, (3) immune cell function, or (4) cell replication. In contrast to β-interferons and glatiramer acetate, the first generation DMTs, several newer therapies are imbued with safety issues. In addition to efficacy, understanding the relationship between the mechanism of action (MOA) of the DMTs and their safety profile is essential for decision-making in patient care. In this article, we relate safety issues of newer DMTs to their pharmacological characteristics, including molecular targets, MOA, chemical structure, and metabolism. Some newer DMTs also represent repurposing or modifications of previous treatments used in other diseases. Here, we describe how identification and understanding of adverse events (AEs) observed with these established drugs within the same class, provide clues regarding safety and toxicities of newer MS therapeutics. While understanding mechanisms underlying DMT toxicities is incomplete, it is important to further develop this knowledge to minimize risk to patients, and to ensure future therapies have the most advantageous risk-benefit profiles. Recognizing the individual classes of DMTs described here may be beneficial when considering use of such agents sequentially and possibly in combination.
登录
查看更多内容
影响因子：
168.9
作者：
Coles, AJ;Wing, N;Compston, A
通讯作者：
Compston, A
DOI：
10.1073/pnas.0601335103
发表时间：
2006-04-11
影响因子：
11.1
作者：
Bielekova, B;Catalfamo, M;Martin, R
通讯作者：
Martin, R
DOI：
10.1073/pnas.0402653101
发表时间：
2004-06-08
影响因子：
11.1
作者：
Bielekova, B;Richert, N;Martin, R
通讯作者：
Martin, R
影响因子：
158.5
作者：
Comi, Giancarlo;Jeffery, Douglas;Filippi, Massimo
通讯作者：
Filippi, Massimo
影响因子：
14.5
作者：
Cotte, S.;von Ahsen, N.;Chan, A.
通讯作者：
Chan, A.