近日，美国食品和药品监督管理局(FDA)批准Tecfidera(富马酸二甲酯)胶囊治疗复发型多发性硬化症(MS)成年。 MS是一种中枢神经系统的慢性，炎症性，破坏大脑和机体其他部分间通信的自身免疫性疾病。它是年轻成年中神经残疾的最常见原因而妇女比男性更频发生。对大多数有MS人们，最初功能恶化发作(复发)接着恢复期(缓解)。随时间，恢复期可能不完全，导致功能进展性下降和残疾增加。MS患者常经受肌肉软弱和难以协调和平衡。大多数人在年龄20和40岁间经历其首次MS症状。 Tecfidera的初始剂量为120mg、2次/d。7天后，推荐剂量增至240mg、2次/d。 FDA药物评价和研究中心神经学产品部主任Russell Katz，M.D.说：“对多发性硬化症没有药物提供治愈所以对于患者重要的是有各种可供选择的治疗，”“多发性硬化症可损害运动，感觉，和思维和对一个人的生活质量产生深远的影响。” 批准日期： 2013年3月27日；公司：Biogen TECFIDERA（富马酸二甲酯[dimethyl fumarate]）缓释胶囊，口服使用 最初美国批准：2013 目前的主要变化 用法与用量，验血之前 治疗开始：1/2017  警告和注意事项，PML：2/2016  警告和注意事项，肝损伤：1/2017 作用机理 由富马酸二甲酯（DMF）在多发性硬化发挥其治疗作用的机理是未知的。DMF中的代谢物，富马酸单甲酯（MMF），已经显示激活核因子（红细胞衍生2）-样2（Nrf2的）在体外和在动物和人体内的通道。该Nrf2的途径参与对氧化应激的细胞应答。MMF已被鉴定为在体外烟酸受体激动剂。 适应症和用法 TECFIDERA被指示为患者的治疗多发性硬化的复发形式 用法用量 起始剂量：120毫克，一天两次，口服，7天 术后7天维持剂量：240毫克，一天两次，口服 燕子TECFIDERA胶囊整体和完整，不要压碎，咀嚼，或撒在食物胶囊，内容物 就拿TECFIDERA带或不带食物 剂型和规格 缓释胶囊：120毫克和240毫克 禁忌症 已知过敏富马酸二甲酯或任何TECFIDERA的辅料。 警告和注意事项 过敏反应和血管性水肿：请停止，如果出现这些情况不重新启动TECFIDERA。 进行性多灶性白质脑病（PML）：在第一个迹象扣压TECFIDERA或症状提示有PML的。 淋巴细胞:启动TECFIDERA之前获取CBC包括淋巴细胞计数，6个月后，每6-12个月后考虑TECFIDERA中断，如果淋巴细胞计数<0.5×109/L持续超过半年。 肝损伤:获取血清氨基转移酶，碱性磷酸酶，总胆红素水平开始TECFIDERA之前和治疗期间，根据临床请停止TECFIDERA如果TECFIDERA引起临床显著肝损伤之嫌。 不良反应 最常见的不良反应（发生率≥10％和≥2％安慰剂）为面部潮红，腹痛，腹泻，恶心。 特殊人群中使用 妊娠：根据动物实验数据，可能会对胎儿造成伤害 包装规格/储存与处理 TECFIDERA可作为含要么120毫克或240毫克的富马酸二甲酯的两个强项硬明胶缓释胶囊。绿色和白色120毫克的胶囊都印有“BG-12120毫克”，在黑色墨水，绿色240毫克胶囊。 都印有黑色墨水TECFIDERA“BG-12240毫克的”可用如下： 30天的入门包，（NDC64406-007-03）： 7天的瓶120毫克胶囊，数量14 23日瓶240毫克胶囊，数量46 120毫克胶囊： 7天一瓶14粒（NDC64406-005-01） 240毫克胶囊： 30天一瓶60粒（NDC64406-006-02） 储存于15°C至30°C（59至86°F）。避光，储存保护胶囊在原容器中。https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=665d7e74-036c-5f68-5b67-ab84b9b49151 TECFIDERA® (Dimethyl Fumarate) Data Reinforce Strong, Sustained Efficacy for Newly-Diagnosed MS Patients TECFIDERA® (dimethyl fumarate) as an effective, long-term treatment for people who are living with relapsing forms of multiple sclerosis (MS). Data show TECFIDERA significantly reduced relapses and disability progression in newly-diagnosed relapsing-remitting MS (RRMS) patients who had highly active disease. Additional data indicate TECFIDERA showed strong and sustained efficacy over five years in RRMS patients who were previously treated with an interferon (interferon beta-1a/b [IFN]) or glatiramer acetate (GA). These results will be presented at the 67th American Academy of Neurology (AAN) Annual Meeting in Washington, D.C. “Taken together, these studies reinforce that TECFIDERA delivers robust efficacy when used as a first-line therapy, as well as when it is used after a patient has discontinued interferon or glatiramer acetate treatment,” said J. Theodore Phillips, M.D., Ph.D., research investigator at the Baylor Institute for Immunology Research and clinical professor of Neurology at the University of Texas Southwestern Medical Center. “In addition, strong efficacy was observed with TECFIDERA treatment in various patient populations including those with highly active MS.” Robust Efficacy in Newly-Diagnosed Patients with Highly Active MS TECFIDERA provided robust efficacy in newly-diagnosed patients who have highly active MS, as seen in a post-hoc analysis of two years of integrated data from the Phase 3 DEFINE and CONFIRM studies. Patients included in the analysis were diagnosed with RRMS within one year prior to enrolling in the DEFINE or CONFIRM studies, were either treatment-naïve or previously treated with corticosteroids alone, and met the criteria for highly active MS (two or more relapses within one year prior to enrolling in DEFINE or CONFIRM). Compared to placebo (n=77) at two years, TECFIDERA (n=84) significantly reduced annualized relapse rate (ARR) (56% reduction, p<0.0040), the proportion of patients who relapsed (56% reduction, p=0.0037) and time to sustained 12-week progression of disability (78% reduction, p=0.0067). “TECFIDERA continues to demonstrate consistently strong efficacy and favorable safety results that we believe support its position as the new oral standard of care,” said Gilmore O’Neill, vice president, Multiple Sclerosis Research and Development at Biogen. “More than 135,000 patients have been treated with TECFIDERA worldwide since it was introduced to the market two years ago.” Long-Term Efficacy of TECFIDERA in Treatment-Naïve Patients and Those with Prior IFN/GA Treatment Experience TECFIDERA provided consistent, long-term efficacy in patients with RRMS who were previously treated with IFN or GA, according to an integrated post-hoc analysis in a subset of patients from the Phase 3 DEFINE, CONFIRM and ENDORSE studies. Patients included in the analysis were followed for a minimum of five years (two years in DEFINE/CONFIRM plus three or more years in ENDORSE). Throughout the study period, the ARR remained low in patients who received continuous treatment with TECFIDERA compared to those who initially received two years of placebo in DEFINE/CONFIRM. In patients who switched from placebo in DEFINE/CONFIRM to TECFIDERA in ENDORSE, improvements were observed in ARR whether they were treatment-naïve or had treated their MS with IFN or GA. •Treatment-naïve patients: ◦Patients receiving five years of TECFIDERA (n=267): ARR was 0.123 (95% confidence interval [CI]: 0.097, 0.157) ◦Patients who switched to TECFIDERA in year three (n=133): ARR was 0.207 (95% CI: 0.152, 0.283) •Patients treated with one or more prior IFN/GA therapy: ◦Patients receiving five years of TECFIDERA (n=124): ARR was 0.195 (95% CI: 0.151, 0.252) ◦Patients who switched to TECFIDERA in year three (n=68): ARR was 0.253 (95% CI: 0.181, 0.353) The safety profile of TECFIDERA observed in ENDORSE in the presented analysis was consistent with the favorable findings reported in the DEFINE and CONFIRM studies, reflecting a minimum of five years of observation. There was no overall increased risk for serious infections, including opportunistic infections. These data will be presented in poster presentations on Thursday, April 23 at 2:00 p.m. ET: •Long-Term Efficacy of Delayed-Release Dimethyl Fumarate for Relapsing-Remitting Multiple Sclerosis According to Prior Therapy: Integrated Analysis of the DEFINE, CONFIRM, and ENDORSE Studies (poster P7.229) •Clinical Efficacy of Delayed-Release Dimethyl Fumarate in Newly Diagnosed Relapsing-Remitting Multiple Sclerosis Patients with Highly Active Disease: An Integrated Analysis of the Phase 3 DEFINE and CONFIRM Studies . 多发性硬化症首选药物TECFIDERA™ (DIMETHYL FUMARATE)获FDA批准上市 2013年3月27日，美国食品药品管理局（FDA）批准百健艾迪旗下Tecfidera（富马酸二甲酯）胶囊用于治疗成人多发性硬化症(MS)复发。 多发性硬化症是一种慢性、炎症性中枢神经系统自身免疫性疾病，能够干扰大脑与身体其他部位之间的信号传递。多发性硬化症也是青壮年神经失能最常见的因素，并且女性的发病率要高于男性。对大多数多发性硬化症患者来说，日益恶化的功能性发作（复发）最初是发生在恢复期（缓解期）之后。随着时间的推移，恢复期可能会变得不完整，导致功能逐渐下降，残疾可能性增加。多发性硬化症患者经常会经历肌无力和协调及平衡困难过程。大多数患者首次出现多发性硬化症症状一般在20至40岁之间。 “现在还没有药物能够治愈多发性硬化症，所以能给患者提供多种治疗选择是非常重要的，” FDA药物评价和研究中心神经类产品部门主管Russell Katz医学博士如此说。“多发性硬化症能够损害人的运动、感觉及思维功能，并对人的生存质量有一种深远的影响。” 两项临床试验结果表明，服用Tecfidera患者与服用安慰剂患者相比，其多发性硬化症的复发变得更少。其中一项试验显示服用Tecfidera的患者其残疾的恶化程度要少于服安慰剂患者。 Tecfidera可能会减少患者的白细胞（淋巴细胞）数。淋巴细胞有助于抵抗感染，而低淋巴细胞计数可能增加感染风险，尽管临床试验过程中没有观察到Tecfidera服药患者有明显增加的感染风险。FDA建议给患者提供医疗保健的机构，在开始治疗之前及之后的每年对患者的白细胞计数进行评价。 临床试验中，接受Tecfidera治疗的患者最常见的副作用有脸红（脸热并发红）和胃部问题（恶心、呕吐、腹泻），主要出现在治疗的初期。这些副作用可能会随时间推移而降低。