Background Women with hereditary angioedema due to C1-inhibitor deficiency (HAE-C1INH) experience more frequent and severe angioedema attacks compared with men. Fluctuations in female sex hormones can influence HAE attack frequency and severity. Subcutaneous C1-INH (C1-INH [SC]) is indicated as routine prophylaxis to prevent HAE attacks. In this post hoc subgroup analysis, we evaluated the efficacy and safety of C1-INH (SC) in female subjects with HAE-C1INH enrolled in an open-label extension of the pivotal phase III COMPACT trial. Methods In this multicenter, randomized, parallel-arm trial, eligible subjects (age ≥ 6 years with ≥ 4 attacks over 2 consecutive months) received C1-INH (SC) 40 IU/kg or 60 IU/kg twice weekly for 52 to 140 weeks. Analyses of efficacy endpoints were performed for all female subjects and those of childbearing age (age ≥ 15 to ≤ 45 years), including subjects who became pregnant during the evaluation period. Results Overall, 91% (69/76) of female subjects were classified as responders (≥ 50% reduction in HAE attacks relative to the pre-study period); 82% experienced < 1 attack/4 weeks. The median number of attacks/month was 0.10, with 96% median reduction in attacks relative to the pre-study period. Results were similar in the subgroup of subjects of childbearing age. Four women who became pregnant during the trial and were exposed to C1-INH (SC) during the first trimester delivered healthy babies with no congenital abnormalities. Conclusions C1-INH (SC) prophylaxis was safe and effective in women with HAE-C1INH, including those of childbearing age. Four women exposed to C1-INH (SC) during the first trimester had uneventful pregnancies and delivered healthy babies.Trial registration Clinicaltrials.gov identifier NCT02316353 (Registered December 10, 2014); https://clinicaltrials.gov/ct2/show/NCT02316353.

中文翻译：

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皮下 C1 抑制剂对遗传性血管性水肿女性的长期疗效和安全性：来自 3 期试验的开放标签扩展的亚组分析。

背景 与男性相比，由于 C1 抑制剂缺乏 (HAE-C1INH) 导致遗传性血管性水肿的女性经历了更频繁和更严重的血管性水肿发作。女性性激素的波动会影响 HAE 的发作频率和严重程度。皮下 C1-INH (C1-INH [SC]) 可作为预防 HAE 发作的常规预防措施。在这项事后亚组分析中，我们评估了 C1-INH (SC) 在参加关键 III 期 COMPACT 试验的开放标签扩展的 HAE-C1INH 女性受试者中的疗效和安全性。方法 在这项多中心、随机、平行臂试验中，符合条件的受试者（年龄 ≥ 6 岁，连续 2 个月内发作 ≥ 4 次）接受 C1-INH (SC) 40 IU/kg 或 60 IU/kg 每周两次，持续 52 至 140周。对所有女性受试者和育龄（年龄≥15至≤45岁）受试者进行疗效终点分析，包括在评估期间怀孕的受试者。结果 总体而言，91% (69/76) 的女性受试者被归类为反应者（与研究前相比，HAE 发作减少 ≥ 50%）；82% 的人经历了 < 1 次发作/4 周。每月攻击次数的中位数为 0.10，与研究前相比，攻击次数中位数减少了 96%。育龄受试者亚组的结果相似。四名在试验期间怀孕并在妊娠前三个月暴露于 C1-INH (SC) 的妇女生下了没有先天性异常的健康婴儿。结论 C1-INH (SC) 预防对 HAE-C1INH 女性（包括育龄女性）安全有效。四名在孕早期暴露于 C1-INH (SC) 的妇女顺利怀孕并分娩了健康的婴儿。试验注册 Clinicaltrials.gov 标识符 NCT02316353（2014 年 12 月 10 日注册）；https://clinicaltrials.gov/ct2/show/NCT02316353。