Duffey Hannah, Firszt Rafael
Department of Pediatrics, University of Utah, Salt Lake City, UT, USA.
Department of Pediatrics, University of Utah, Salt Lake City, UT, USA ; Division of Allergy, Immunology and Rheumatology, University of Utah, Salt Lake City, UT, USA.
J Blood Med. 2015 Apr 16;6:115-23. doi: 10.2147/JBM.S66825. eCollection 2015.
Hereditary angioedema (HAE) is characterized as an episodic swelling disorder with autosomal dominant inheritance. Clinical features include nonpitting edema of external or mucosal body surfaces, and patients often present with swelling of the extremities, abdominal pain, and swelling of the mouth and throat, which can lead to asphyxiation. Patients with HAE classically have no associated urticaria, which is often referred to as nonhistaminergic angioedema. Treatment for HAE involves long-term prophylaxis, short-term prophylaxis, and management of acute attacks. Up until the past few years, acute HAE episodes were predominately treated with supportive measures. Three classes of medications have recently been approved by the US Food and Drug Administration (FDA) for the management of acute HAE attacks. Ecallantide, a recombinant protein that acts as a reversible inhibitor of kallikrein, is currently indicated for acute attacks of HAE in those aged ≥12 years. In two randomized, double-blind, placebo-controlled, multicenter trials, EDEMA3 and EDEMA4, patients treated with 30 mg of ecallantide demonstrated statistically significant improvement in symptoms compared to those on placebo. In addition to its use as treatment for HAE, ecallantide has been used off label in the management of nonhistaminergic angioedema, not due to HAE. Ecallantide has shown promise in the treatment of these other forms; however, data are limited to mainly case reports at this time. Ecallantide is generally a safe and well-tolerated medication; however, based on reports of anaphylaxis, ecallantide does contain a black box warning. Due to the risk of anaphylaxis, ecallantide cannot be self-administered and must be given by a health care professional. Overall, ecallantide is a safe and effective medication for the treatment of acute attacks of HAE.
遗传性血管性水肿(HAE)的特征是一种具有常染色体显性遗传的发作性肿胀疾病。临床特征包括体表或黏膜非凹陷性水肿,患者常出现四肢肿胀、腹痛以及口腔和咽喉肿胀,后者可导致窒息。HAE患者通常无相关荨麻疹,这常被称为非组胺能性血管性水肿。HAE的治疗包括长期预防、短期预防以及急性发作的处理。直到过去几年,急性HAE发作主要采用支持性措施治疗。最近美国食品药品监督管理局(FDA)批准了三类药物用于治疗急性HAE发作。依库丽单抗是一种重组蛋白,作为激肽释放酶的可逆抑制剂,目前适用于≥12岁患者的HAE急性发作。在两项随机、双盲、安慰剂对照的多中心试验EDEMA3和EDEMA4中,接受30mg依库丽单抗治疗的患者与接受安慰剂治疗的患者相比,症状有统计学意义的显著改善。除了用于治疗HAE外,依库丽单抗还被用于非HAE所致非组胺能性血管性水肿的管理,但属于超说明书用药。依库丽单抗在治疗这些其他形式的疾病方面已显示出前景;然而,目前数据主要限于病例报告。依库丽单抗总体上是一种安全且耐受性良好的药物;然而,基于过敏反应报告,依库丽单抗确实包含黑框警告。由于存在过敏反应风险,依库丽单抗不能自行给药,必须由医疗保健专业人员给药。总体而言,依库丽单抗是治疗HAE急性发作的一种安全有效的药物。