Epstein Tolly G, Bernstein Jonathan A
Department of Internal Medicine, Division of Immunology/Allergy, University of Cincinnati Medical Center, Cincinnati, Ohio 45267-0563, USA.
Drugs. 2008;68(18):2561-73. doi: 10.2165/0003495-200868180-00003.
Hereditary angioedema (HAE) is a rare disorder characterized by recurrent attacks of swelling that may involve multiple anatomical locations. In the majority of patients, it is caused by a functional or quantitative defect in the C1 inhibitor (C1-INH), which is an important regulator of the complement, fibrinolytic, kallikrein-kinin and coagulation systems. Standard treatments used for other types of angioedema are ineffective for HAE. Traditional therapies for HAE, including fresh frozen plasma, epsilon-aminocaproic acid and danazol, may be well tolerated and effective in some patients; however, there are limitations both in their safety and efficacy. Several novel therapies have completed phase III trials in the US, including: (i) plasma-derived C1-INH replacement therapies (Berinert P and Cinryze); (ii) a recombinant C1-INH replacement therapy (conestat alfa; Rhucin); (iii) a kallikrein inhibitor (ecallantide [DX-88]); and (iv) a bradykinin-2-receptor antagonist (icatibant). Both Berinert P and Cinryze are reported to have excellent efficacy and safety data from phase III trials. Currently, only Cinryze has been approved for prophylactic use in the US. US FDA approval for other novel agents to treat HAE and for the use of Cinryze in the treatment of acute attacks is pending.
遗传性血管性水肿（HAE）是一种罕见的疾病，其特征为反复出现的肿胀发作，可累及多个解剖部位。在大多数患者中，该病由C1抑制剂（C1-INH）的功能或定量缺陷引起，C1-INH是补体、纤维蛋白溶解、激肽释放酶-激肽和凝血系统的重要调节因子。用于其他类型血管性水肿的标准治疗方法对HAE无效。HAE的传统疗法，包括新鲜冷冻血浆、ε-氨基己酸和达那唑，在一些患者中可能耐受性良好且有效；然而，它们在安全性和有效性方面都存在局限性。几种新型疗法已在美国完成III期试验，包括：（i）血浆源性C1-INH替代疗法（贝林妥欧P和Cinryze）；（ii）重组C1-INH替代疗法（康奈单抗；Rhucin）；（iii）激肽释放酶抑制剂（依卡奈珠单抗[DX-88]）；以及（iv）缓激肽-2受体拮抗剂（艾替班特）。据报道，贝林妥欧P和Cinryze在III期试验中均有出色的疗效和安全性数据。目前，在美国只有Cinryze被批准用于预防。美国食品药品监督管理局（FDA）对其他治疗HAE的新型药物以及Cinryze用于治疗急性发作的批准尚在等待中。
