Tecfidera获准用于复发型多发性硬化症

圣路易斯(MD Consult)——2013年3月27日，美国食品药品管理局(FDA)与Biogen宣布，Tecfidera(富马酸二甲酯)已获准成为复发型多发性硬化症(MS)的一线口服治疗药物。据称，Tecfidera采用了一种新的MS治疗途径——通过激活核因子(红系衍生性)2样通路发挥作用，不过其确切的作用机制尚不清楚。这一通路使得体内细胞有能力抵御伴随MS等疾病而来的炎症和氧化应激的伤害。

FDA批准Tecfidera是基于一项临床研发计划的数据，包括2项全球性3期研究，共招募了超过2,600例患者。在目前仍在进行、正处于延长期的研究中，部分接受Tecfidera治疗的患者已经被随访了4年以上。

在一项3期试验中，2年时，每日2次Tecfidera(与安慰剂比较)可使复发患者所占比例显著降低49%(P＜0.0001)，使年化复发率(ARR)降低53%(P＜0.0001)，使12周明确残疾进展减少38%(P=0.005)。在另一项3期研究中，2年时，每日2次Tecfidera(与安慰剂比较)可使ARR减少44%(P＜0.0001)，使复发患者所占比例降低34%(P=0.002)。尽管不具有统计学显著性，但在第二项研究中，使用Tecfidera与12周明确残疾进展减少21%有关。在两项研究中，使用Tecfidera的患者还能显著减少脑内病变(根据MRI影像判断)。

与使用Tecfidera相关的最常见不良反应为面部潮红(绝大多数为轻至中度)和消化道事件(例如腹泻、恶心、腹痛)。

Tecfidera可能减少淋巴细胞计数。在开始治疗之前，应回顾近期的全血细胞计数(CBC)。建议每年和有临床指征时进行CBC检查。Tecfidera在淋巴细胞计数本已偏低的患者中的应用尚未得到研究，对这类患者使用该药必须谨慎。

Tecfidera的初始剂量为120 mg、2次/d。7天后，推荐剂量增至240 mg、2次/d。

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ST LOUIS (MD Consult) - On March 27, 2013, the US Food and Drug Administration (FDA) and Biogen annnounced the approval of Tecfidera (dimethyl fumarate), a first-line oral treatment of relapsing forms of multiple sclerosis (MS). It is believed that Tecfidera provides a new approach to treating MS by activating the Nuclear factor (erythroid-derived 2)-like 2 pathway, though its exact mechanism of action is unknown. This pathway provides a way for cells in the body to defend themselves against inflammation and oxidative stress associated with conditions such as MS.

The FDA approval of Tecfidera was granted on the basis of data from a clinical development program that included 2 global phase 3 studies that enrolled included more than 2,600 patients. In the ongoing extension study, some patients receiving Tecfidera have been followed for longer than 4 years.

After 2 years, in one of the phase 3 trials, the use of twice-daily Tecfidera (compared with placebo) significantly reduced the proportion of patients who relapsed by 49% (P < .0001), the annualized relapse rate (ARR) was reduced by 53% (P < .0001), and 12-week confirmed disability progression was reduced by 38% (P = .0050). In the second phase 3 study, the use of twice-daily Tecfidera was associated with a 44% reduction (P < .0001) in ARR, and the proportion of patients who experienced relapse was reduced by 34% (P = .0020), compared with placebo at 2 years. While not statistically significant, the use of Tecfidera in the second study was associated with a 21% reduction in 12-week confirmed disability progression. Patients who received Tecfidera in both studies also exhibited significantly reduced lesions in the brain compared with placebo, as measured by magnetic resonance imaging.

The most common adverse reactions associated with the use of Tecfidera were flushing, mostly mild to moderate in nature, and gastrointestinal events (ie,, diarrhea, nausea, abdominal pain). These events were more common at the start of therapy and usually decreased over time.

Tecfidera use may decrease lymphocyte counts. Before starting treatment, a recent complete blood count (CBC) should be reviewed. A CBC is recommended annually and as clinically indicated. Tecfidera has not been studied in patients with pre-existing low lymphocyte counts and caution should be exercised when treating these patients.

The starting dose for Tecfidera is 120 mg twice daily. After 7 days, the recommended dose increases to 240 mg twice daily.