Department of Dermatology, Ernst von Bergmann General Hospital, Teaching Hospital Charité, Humboldt University, Charlottenstrasse 72, 14467, Potsdam, Germany.
Department of Dermatology, Venerology and Allergology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Arch Dermatol Res. 2018 Aug;310(6):475-483. doi: 10.1007/s00403-018-1825-9. Epub 2018 Mar 24.
Fumarates (fumaric acid esters, FAEs) are orally administered systemic agents used for the treatment of psoriasis and multiple sclerosis. In 1994, a proprietary combination of FAEs was licensed for psoriasis by the German Drug Administration for use within Germany. Since then, fumarates have been established as one of the most commonly used treatments for moderate-to-severe psoriasis in Germany and other countries. The licensed FAE formulation contains dimethyl fumarate (DMF), as well as calcium, zinc, and magnesium salts of monoethyl fumarate (MEF). While the clinical efficacy of this FAE mixture is well established, the combination of esters on which it is based, and its dosing regimen, was determined empirically. Since the mid-1990s, the modes of action and contribution of the different FAEs to their overall therapeutic effect in psoriasis, as well as their adverse event profile, have been investigated in more detail. In this article, the available clinical data for DMF are reviewed and compared with data for the other FAEs. The current evidence substantiates that DMF is the main active compound, via its metabolic transformation to monomethyl fumarate (MMF). A recent phase III randomized and placebo-controlled trial including more than 700 patients demonstrated therapeutic equivalence when comparing the licensed FAE combination with DMF alone, in terms of psoriasis clearance according to the Psoriasis Area and Severity Index (PASI) and Physician's Global Assessment (PGA). Thus, DMF as monotherapy for the treatment of psoriasis is as efficacious as in combination with MEF, making the addition of such fumarate derivatives unnecessary.
富马酸盐（富马酸酯，FAE）是一种口服全身药物，用于治疗银屑病和多发性硬化症。1994 年，德国药品管理局为德国境内使用特批了一种 FAEs 的专有组合用于治疗银屑病。从那时起，富马酸盐已成为德国和其他国家治疗中重度银屑病最常用的方法之一。许可的 FAE 配方包含富马酸二甲酯（DMF）以及富马酸单乙酯（MEF）的钙、锌和镁盐。虽然这种 FAE 混合物的临床疗效已经得到充分证实，但它所基于的酯的组合及其剂量方案是通过经验确定的。自 20 世纪 90 年代中期以来，人们对不同 FAEs 在银屑病中的作用模式及其对整体治疗效果的贡献，以及它们的不良事件谱进行了更详细的研究。本文回顾了 DMF 的现有临床数据，并与其他 FAEs 的数据进行了比较。目前的证据证实，DMF 是主要的活性化合物，通过其代谢转化为单甲基富马酸（MMF）。最近的一项包括 700 多名患者的 III 期随机安慰剂对照试验表明，在根据银屑病面积和严重程度指数（PASI）和医生总体评估（PGA）评估的银屑病清除方面，许可的 FAE 组合与 DMF 单独使用具有治疗等效性。因此，DMF 作为银屑病的单一疗法与与 MEF 联合使用一样有效，使得添加此类富马酸衍生物变得不必要。
