英文药名：Amevive(Alefacept Intramuscular Injection) 中文药名：阿法赛特注射剂 生产厂家：Biogen Inc. 给药说明 Alefacept副作用;别名:Amevive;Alefacept适应症:本品用于成年人中、重度慢性斑块型银屑病。;Alefacept药理学作用:本品为一种免疫抑制性二聚物融合蛋白，由人类白细胞功能相关抗原-3(LFA-3)与CD2结合的细胞外部分与人类IgG1的Fc(枢纽，CH2和CH3区)部分结合组成，分子质量91.4×103Da。本品是一种免疫调节剂，通过特异性与淋巴细胞抗原CD2结合并抑制LFA-3与CD2的相互作用，从而影响淋巴细胞活化。本品能选择性地作用于银屑病及其他自身免疫紊乱介质——记忆性T细胞(CD45RO+细胞)，减少这些致病细胞的数量，而对正常免疫功能没有影响。 分类名称 一级分类：皮肤科用药 二级分类：免疫调节剂 三级分类：免疫抑制剂    药品英文名 Alefacept   药品别名 Amevive   药物剂型 注射剂：7.5mg/支(供静脉注射)，15mg/支(供肌内注射)，分别附溶剂0.5ml(内含蔗糖12.5mg，氨基乙酸5mg，二水合枸橼酸钠3.6mg，一水合枸橼酸钠0.06mg)。   药理作用 本品为一种免疫抑制性二聚物融合蛋白，由人类白细胞功能相关抗原-3(LFA-3)与CD2结合的细胞外部分与人类IgG1的Fc(枢纽，CH2和CH3区)部分结合组成，分子质量91.4×103Da。本品是一种免疫调节剂，通过特异性与淋巴细胞抗原CD2结合并抑制LFA-3与CD2的相互作用，从而影响淋巴细胞活化。本品能选择性地作用于银屑病及其他自身免疫紊乱介质——记忆性T细胞(CD45RO+细胞)，减少这些致病细胞的数量，而对正常免疫功能没有影响。   药动学 中等程度银屑病患者静注本品7.5mg，平均表观分布容积为94ml/kg，清除率为0.25ml/(kg·h)，消除半衰期为270h；肌注生物利用度为63%。   适应证 本品用于成年人中、重度慢性斑块型银屑病。   禁忌证 1．对本品及其组分过敏者禁用。 2．尚无儿童用药安全性资料，儿童禁用。 3．肝、肾功能不全者禁用。 4．正在使用免疫抑制剂或光疗者不能使用本品。   注意事项 1．本品必须在医生监督指导下使用。 2．本品为免疫抑制剂，可能会增加感染复发机会和引起慢性感染，治疗中应检测是否出现感染体征和症状，一旦出现严重感染应立即停药。 3．超剂量使用应密切观察淋巴细胞和CD4+T淋巴细胞记数。 4．用药期间及停药8周内怀孕应立即告诉医生。 5．室温，避光，干燥处保存。   不良反应 慢性银屑病患者重复应用本品耐受良好，常见不良反应有淋巴细胞减少、恶性肿瘤发生机会增加，可引起严重感染及过敏反应。其他不良反应有咽炎、头昏、咳嗽、恶心、瘙痒、肌痛、寒战，注射部位可出现疼痛及炎症反应。使用最大剂量(0.75mg/kg静注)后可出现寒战、头痛、关节痛、鼻窦炎等症状。部分患者出现抗-Alefacept抗体。   用法用量 静注，每次7.5mg，每周1次，12周为1个疗程。肌注，每次15mg，每周1次，12周为1个疗程。两疗程之间至少间隔12周。   药物相应作用 不与其他免疫抑制剂同时使用。 Drugs Approved by the FDA Drug Name: Amevive (alefacept) Company: Biogen Approval Status: Approved January 2003 Treatment for: Psoriasis General Information Amevive (alefacept) is an immunosuppressive dimeric fusion protein that reduces lymphocyte counts (T-cells) thus treating the cause of psoriasis. It is indicated in patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy Amevive is available in either intramuscular injection (15-mg alefacept) or intravenous injection (7.5-mg alefacept) formulations. Amevive reduces immune cell counts which could increase the chance of developing infection or malignancy. Clinical Results Amevive was evaluated in two randomized, double blind, placebo-controlled studies in 726 adult subjects with chronic plaque psoriasis. In both trials, Amevive or placebo was administered once a week for 12 weeks. In total 77% of subjects had previously received systemic therapy and/or phototherapy for psoriasis. Response to treatment in both studies was defined as the proportion of subjects with a reduction in score on the Psoriasis Area and Severity Index (PASI)?of at least 75% from baseline at two weeks following the 12-week treatment period. Other treatment responses included the proportion of subjects who achieved a scoring of 'almost clear' or 'clear' by Physician Global Assessment (PGA) and the proportion of subjects with a reduction in PASI of at least 50% from baseline two weeks after the 12-week treatment period. In both studies, onset of response to Amevive treatment (at least a 50% reduction of baseline PASI) began 60 days after the start of therapy. In Study 1, the median duration of response (75% or greater reduction in PASI) was 3.5 months for Amevive treated patients and 1 month for placebo-treated patients. In Study 2, the median duration of response was approximately 2 months for both groups. A majority of the subjects had responded to either Amevive or placebo maintained a 50% or greater reduction in PASI through the 3-month observation period. In both studies, an additional 11% (42/367) and 7% (12/166) of subjects treated with Amevive, respectively, achieved a 75% reduction from baseline PASI score at one or more visits after the first 2 weeks of the follow-up period. Side Effects Adverse events associated with the use of Amevive may include (but are not limited to) the following: Serious Infections Malignancies Lymphopenia Sore throat Dizziness Cough Nausea Itching Muscle Aches Chills Injection Site Pain Injection Site Inflammation Accidental injury Mechanism of Action Amevive (alefacept) is an immunosuppressive dimeric fusion protein that consists of the extracellular CD2-binding portion of the human leukocyte function antigen-3 (LFA-3) linked to the Fc (hinge, CH2 and CH3 domains) portion of human IgG1. Alefacept is produced by recombinant DNA technology in a Chinese Hamster Ovary (CHO) mammalian cell expression system. Amevive interferes with lymphocyte activation by specifically binding to the lymphocyte antigen, CD2, and inhibiting LFA-3/CD2 interaction. Activation of T lymphocytes involving the interaction between LFA-3 on antigen-presenting cells and CD2 on T lymphocytes plays a role in the pathophysiology of chronic plaque psoriasis. The majority of T lymphocytes in psoriatic lesions are of the memory effector phenotype characterized by the presence of the CD45RO marker? express activation markers (e.g., CD25, CD69) and release inflammatory cytokines, such as interferon y. Amevive also causes a reduction in subsets of CD2+ T lymphocytes (primarily CD45RO+), presumably by bridging between CD2 on target lymphocytes and immunoglobulin Fc receptors on cytotoxic cells, such as natural killer cells. Treatment with Amevive results in a reduction in circulating total CD4+ and CD8+ T lymphocyte counts. CD2 is also expressed at low levels on the surface of natural killer cells and certain bone marrow B-lymphocytes. 免疫调节剂『Amevive』获美国食品及药物管理局（FDA）批准的又一种牛皮癣新药 Amevive，属名为alefacept，是唯一用于治疗中度及严重噬斑型牛皮癣成人患者。 Amevive的作用机制是减少与牛皮癣有关的免疫性反应，后者会增加皮肤感染甚至发生恶性病变的危险。FDA是根据最近完成的两项双盲随机临床治疗结果做出上述批准的。这两项研究总共涉及到1,060例慢性噬斑型牛皮癣成人患者，结果表明Amevive组患者的病变皮肤面积、病变程度以及与此有关的炎症反应都要比对照组得到更为显著的改善。可能发生的副作用包括咽喉痛、眩晕、咳嗽、恶心以及肌肉酸痛等。鉴于目前还不大清楚该药对妊娠的影响，有关专家建议孕妇应当与AME-VIVE药厂(Biogen公司)取得联系，以便后者监测可能对胎儿发生的任何副作用。此外专家们还提醒说，患者在接受Amevive治疗期间还需要定期检查白细胞数。 Amevive(alefacept)-新一代银屑病治疗注射剂治疗中重度慢性银屑病注射针剂获FDA美国食品药物管理局批准上市 Amevive是美国Biogen公司生产制造的新一代银屑病治疗药品,在经历了数年的试验后,今年5月23日,在FDA举办的专家评议会上,十位专家以8票同意,2票反对的投票率通过了对它的审批。这是FDA有史以来第一次批准生物药品用于寻常型银屑病治疗。 Amevive是一种生物药品,是蛋白质,与传统的化学制药制造出的具有严格化学分子式的小分子药品(比如维甲酸、环胞素、钙泊三醇等)完全不同。新型的生物药品制造出的药品都是蛋白质大分子,因为胃肠会把蛋白质分解为氨基酸,所以这一类通常只能通过注射方式给药,不能口服。生物药品的好处是可以作用于人体生命活动的某一个具体环节,比如amevive就是直接作用于人体免疫系统的T细胞,从而中断银屑病的发生过程。因此从原理上讲,它的副作用比化学药品要小,化学药品的作用范围一般都是全身性的。现在还有多种治疗银屑病的生物药品正处于研发和试验阶段,Amevive是这批药物中进入实用的第一个。可以预言,生物药品将是今后几年内国外银屑病科研及治疗的主要方向之一。 在Amevive二期的临床试验过程中,曾引起了各方的关注,据称其有效率相当的高,可以接近60%。当然事物总有一个发展过程,作为第一种治疗寻常型银屑病的生物药品,它可能还有很多不足,对长期的副作用的担忧、价格等可能都会影响它的推广。