阿法赛特Amevive（alefacept）美国食品药物管理局 2003年1月批准上市。 Amevive (alefacept)新一代银屑病治疗药品治疗中重度慢性银屑病注射针剂。 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。   Drugs Approved by the FDA 药品名称：Amevive（alefacept） The following information is obtained from various newswires, published medical journal articles, and medical conference presentations. 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 Amevive (alefacept) 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. Literature References Bos JD, Hagenaars C, Das PK, et al. Predominance of 'memory' T cells (CD4+, CDw29+) over 'na飗e' T cells (CD4+, CD45R+) in both normal and diseased human skin. Arch Dermatol Res 1989; 281:24-30. Ellis C, Krueger GG. Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes. N Engl J Med 2001; 345:248-255. Fredriksson T, Pettersson U. Severe psoriasis--oral therapy with a new retinoid. Dermatologica 1978; 157:238-244. Additional Information For additional information regarding Amevive or psoriasis, please contact 英文药名: Amevive (Alefacept Intramuscular Injection) 中文药名: 阿法赛特肌内注射液 生产厂家: Biogen Inc 药物名称 通用名： 阿法 品牌名称：赛特 生产厂家 Biogen Inc. 适应症 该药物是用于治疗中度至重度慢性斑块型银屑病 使用方法 严格按照规定使用这种药物。 这种药物是由医疗专业人士每周一次给予肌肉注射（IM）的。 如果您有任何疑问，请遵医嘱。 注意事项 在使用这种药物时，如果您有：癌症，感染史，目前正接受化疗, 请咨询您的医生或药剂师。 使用这种药物时，请告诉您的医生或药剂师您的病史，尤其是：经常性感染（如肺炎 ，皮肤感染），免疫系统疾病（免疫抑制），任何过敏; 没有免疫/未经医生同意接种疫苗，避免与口服小儿麻痹症疫苗的人接触。 这种药物可能引起晕眩，谨慎从事一些活动: 如驾驶或使用机器。 这种药物不应使用于儿童。 老年人: 谨慎对待，因为他们可能更敏感，容易产生副作用。 目前还不清楚这种药物是否进入母乳, 母乳喂哺者不建议使用这种药物。 药物相互作用 在使用此药，请告诉您的医生或药剂师, 您正使用的处方药和非处方药. 特别是：药物可能抑制免疫系统（如癌症化疗 ， 泼尼松 ，环孢素），活疫苗等。 不良反应 可能包括（但不限于）以下内容： 严重感染 恶性肿瘤 淋巴细胞 喉咙痛 头晕 咳嗽 恶心 发痒 肌肉酸痛 发冷 注射部位疼痛 注射部位炎症 意外伤害 储藏 室温15-30摄氏度避光保存。 远离儿童和宠物。