Efficacy of recombinant human C1 esterase inhibitor for the treatment of severe hereditary angioedema attacks.
Efficacy of recombinant human C1 esterase inhibitor for the treatment of severe hereditary angioedema attacks.
复制标题
重组人 C1 酯酶抑制剂治疗严重遗传性血管性水肿发作的疗效。
DOI：
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发表时间：
2017
影响因子：
2.8
通讯作者：
A. Relan
中科院分区：
文献类型：
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作者：
H. Li;A. Reshef;J. Baker;J. Harper;A. Relan
背景
遗传性血管性水肿（HAE）的严重发作会使人衰弱并可能危及生命，并会增加焦虑和医疗资源的使用。
目的
该事后评估评价了用于治疗急性重度HAE发作的重组人C1酯酶抑制剂（rhC 1-INH）。
方法
在一项双盲、随机对照试验（RCT）中，HAE发作（基线视觉模拟量表评分≥50 mm，重度发作定义为≥75 mm）的患者被随机分配接受rhC 1-INH（体重<84 kg的患者为50 IU/kg;体重≥84 kg的患者为4200 IU）或安慰剂。此外，在rhC 1-INH的开放标签扩展（OLE）研究中，分析了口咽-喉发作。4小时后或危及生命的症状（RCT中）或1小时后（OLE研究中）允许使用rhC 1-INH 50 IU/kg（≤4200 IU）进行补救治疗。主要终点采用治疗效果问卷测量至症状开始缓解的时间。
结果
在随机对照试验的75名成年人中，43名患有严重发作，并接受rhC 1-INH（n = 24）或安慰剂（n = 19）。rhC 1-INH和安慰剂组至症状缓解发作的中位时间（95%置信区间）分别为90.0分钟（95%置信区间，47.0-120.0分钟）和334.0分钟（95%置信区间，105.0至无法计算的分钟;风险比，2.5; p = 0.02）。rhC 1-INH组24例患者中有1例（4.2%）和安慰剂组19例患者中有10例（52.6%）接受了开放标签rhC 1-INH补救治疗。在OLE研究期间，8次口咽-喉HAE发作的rhC 1-INH症状缓解的中位起效时间为69.0分钟（95%置信区间，59.0-91.0分钟）。
结论
在目前的研究中，rhC 1-INH在解决严重HAE发作（包括口咽-喉发作）方面有效。rhC 1-INH补救治疗迅速改善了接受安慰剂和经历恶化或持续症状的患者的症状。
BACKGROUND
Severe attacks of hereditary angioedema (HAE) are debilitating and potentially life threatening, and can increase anxiety and the use of medical resources.
OBJECTIVE
This post hoc assessment evaluated recombinant human C1 esterase inhibitor (rhC1-INH) used to treat acute severe HAE attacks.
METHODS
In a double-blind, randomized-controlled trial (RCT), patients with an HAE attack (baseline visual analog scale score of ≥50 mm, with severe attacks defined as ≥75 mm) were randomly assigned to receive rhC1-INH (50 IU/kg for patients who weighed <84 kg; 4200 IU for patients who weighed ≥84 kg) or placebo. Also, in an open-label extension (OLE) study of rhC1-INH, oropharyngeal-laryngeal attacks were analyzed. Rescue therapy with rhC1-INH 50 IU/kg (≤4200 IU) was permitted after 4 hours or for life-threatening symptoms (in the RCT) or after 1 hour (in the OLE study). The primary end point measured the time to the beginning of symptom relief by using the Treatment Effects Questionnaire.
RESULTS
Of 75 adults in the RCT, 43 had severe attacks and received either rhC1-INH (n = 24) or placebo (n = 19). The median (95% confidence interval) time to the onset of symptom relief totaled 90.0 minutes (95% confidence interval, 47.0-120.0 minutes) versus 334.0 minutes (95% confidence interval, 105.0 to not calculable minutes; hazard ratio, 2.5; p = 0.02), for rhC1-INH and placebo, respectively. Open-label rhC1-INH rescue therapy was administered to 1 of 24 in the rhC1-INH group (4.2%) and 10 of 19 in the placebo group (52.6%). During the OLE study, the median onset of symptom relief with rhC1-INH for eight oropharyngeal-laryngeal HAE attacks was 69.0 minutes (95% confidence interval, 59.0-91.0 minutes).
CONCLUSION
In the current study, rhC1-INH was efficacious in resolving severe HAE attacks, including oropharyngeal-laryngeal attacks. The rhC1-INH rescue treatment rapidly improved symptoms for patients who received placebo and who experienced worsening or sustained symptoms.