Miller David H, Fox Robert J, Phillips J Theodore, Hutchinson Michael, Havrdova Eva, Kita Mariko, Wheeler-Kingshott Claudia A M, Tozer Daniel J, MacManus David G, Yousry Tarek A, Goodsell Mary, Yang Minhua, Zhang Ray, Viglietta Vissia, Dawson Katherine T
From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre; University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK; Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH; Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX; St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland; Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic; Virginia Mason Medical Center (M.K.), Seattle, WA; CircleScience (M.G.), Tytherington, UK; and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA.
Neurology. 2015 Mar 17;84(11):1145-52. doi: 10.1212/WNL.0000000000001360. Epub 2015 Feb 13.
To evaluate the effects of oral delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) on MRI lesion activity and load, atrophy, and magnetization transfer ratio (MTR) measures from the Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis (CONFIRM) study.
CONFIRM was a 2-year, placebo-controlled study of the efficacy and safety of DMF 240 mg twice (BID) or 3 times daily (TID) in 1,417 patients with relapsing-remitting multiple sclerosis (RRMS); subcutaneous glatiramer acetate 20 mg once daily was included as an active reference comparator. The number and volume of T2-hyperintense, T1-hypointense, and gadolinium-enhancing (Gd+) lesions, as well as whole brain volume and MTR, were assessed in 681 patients (MRI cohort).
DMF BID and TID produced significant and consistent reductions vs placebo in the number of new or enlarging T2-hyperintense lesions and new nonenhancing T1-hypointense lesions after 1 and 2 years of treatment and in the number of Gd+ lesions at week 24, year 1, and year 2. Lesion volumes were also significantly reduced. Reductions in brain atrophy and MTR changes with DMF relative to placebo did not reach statistical significance.
The robust effects on MRI active lesion counts and total lesion volume in patients with RRMS demonstrate the ability of DMF to exert beneficial effects on inflammatory lesion activity in multiple sclerosis, and support DMF therapy as a valuable new treatment option in RRMS.
This study provides Class I evidence of reduction in brain lesion number and volume, as assessed by MRI, over 2 years of delayed-release DMF treatment.
通过复发缓解型多发性硬化症（RRMS）的比较剂和口服富马酸盐（CONFIRM）研究，评估口服缓释富马酸二甲酯（DMF；也称为肠溶型DMF）对MRI病变活性和负荷、萎缩以及磁化传递率（MTR）测量的影响。
CONFIRM是一项为期2年的安慰剂对照研究，研究对象为1417例复发缓解型多发性硬化症（RRMS）患者，比较240mg DMF每日两次（BID）或每日三次（TID）的疗效和安全性；皮下注射每日一次20mg醋酸格拉替雷作为活性对照比较剂。在681例患者（MRI队列）中评估T2高信号、T1低信号和钆增强（Gd+）病变的数量和体积，以及全脑体积和MTR。
在治疗1年和2年后，与安慰剂相比，DMF BID和TID使新的或扩大的T2高信号病变和新的非强化T1低信号病变的数量显著且持续减少，在第24周、第1年和第2年时Gd+病变的数量也显著减少。病变体积也显著减小。与安慰剂相比，DMF导致的脑萎缩和MTR变化的减少未达到统计学显著性。
对RRMS患者MRI活性病变计数和总病变体积的显著影响表明，DMF能够对多发性硬化症的炎症性病变活性产生有益影响，并支持将DMF治疗作为RRMS中有价值的新治疗选择。
本研究提供了I类证据，证明在超过2年的缓释DMF治疗中，通过MRI评估脑病变数量和体积减少。
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