Gold Ralf, Giovannoni Gavin, Phillips J Theodore, Fox Robert J, Zhang Annie, Meltzer Leslie, Kurukulasuriya Nuwan C
St. Josef Hospital, Ruhr University, Germany
Queen Mary University of London, Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK.
Mult Scler. 2015 Jan;21(1):57-66. doi: 10.1177/1352458514537013. Epub 2014 Jul 2.
Delayed-release dimethyl fumarate (DMF) demonstrated efficacy and safety in the Phase 3 DEFINE and CONFIRM trials.
To evaluate delayed-release DMF in newly diagnosed relapsing-remitting multiple sclerosis (RRMS) patients, in a post-hoc analysis of integrated data from DEFINE and CONFIRM.
Patients included in the analysis were diagnosed with RRMS within 1 year prior to study entry and naive to MS disease-modifying therapy.
The newly diagnosed population comprised 678 patients treated with placebo (n = 223) or delayed-release DMF 240 mg BID (n = 221) or TID (n = 234). At 2 years, delayed-release DMF BID and TID reduced the annualized relapse rate by 56% and 60% (both p < 0.0001), risk of relapse by 54% and 57% (both p < 0.0001), and risk of 12-week confirmed disability progression by 71% (p < 0.0001) and 47% (p = 0.0085) versus placebo. In a subset of patients (MRI cohort), delayed-release DMF BID and TID reduced the mean number of new or enlarging T2-hyperintense lesions by 80% and 81%, gadolinium-enhancing lesion activity by 92% and 92%, and mean number of new non-enhancing T1-hypointense lesions by 68% and 70% (all p < 0.0001 versus placebo). Flushing and gastrointestinal events were associated with delayed-release DMF.
Delayed-release DMF improved clinical and neuroradiological outcomes relative to placebo in newly diagnosed RRMS patients.
缓释富马酸二甲酯（DMF）在3期DEFINE和CONFIRM试验中显示出疗效和安全性。
在DEFINE和CONFIRM综合数据的事后分析中，评估缓释DMF在新诊断的复发缓解型多发性硬化症（RRMS）患者中的疗效。
纳入分析的患者在研究入组前1年内被诊断为RRMS，且未接受过MS疾病修饰治疗。
新诊断人群包括678例接受安慰剂治疗的患者（n = 223）、接受240 mg缓释DMF每日两次治疗的患者（n = 221）或每日三次治疗的患者（n = 234）。在2年时，与安慰剂相比，缓释DMF每日两次和每日三次治疗分别使年化复发率降低了56%和60%（均p < 0.0001），复发风险降低了54%和57%（均p < 0.0001），12周确诊残疾进展风险降低了71%（p < 0.0001）和47%（p = 0.0085）。在一部分患者（MRI队列）中，缓释DMF每日两次和每日三次治疗分别使新的或扩大的T2高信号病灶平均数量减少了80%和81%，钆增强病灶活性减少了92%和92%，新的非增强T1低信号病灶平均数量减少了68%和70%（与安慰剂相比均p < 0.0001）。潮红和胃肠道事件与缓释DMF有关。
相对于安慰剂，缓释DMF在新诊断的RRMS患者中改善了临床和神经放射学结局。
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