Safety data on the use of monoclonal antibodies inhibiting proprotein convertase subtilisin/kexin type 9 in pregnancy are scarce. This study queried VigiBase®, the World Health Organization global pharmacovigilance database, to search for signals of disproportionate reporting for pregnancy outcomes with alirocumab and evolocumab. As of November 22, 2023, there were 45 safety reports of exposure to evolocumab (N = 31) and alirocumab (N = 14) in pregnancy. Most of them originated from Europe (N = 25, 55.6%) and were more frequently reported by healthcare professionals (N = 35, 77.8%). Median patient age was 37 years (25th–75th percentiles; 32–41 years). Drug exposure occurred during pregnancy in 36 (80.0%) safety reports, via paternal exposure during pregnancy in four (8.9%), during lactation in three (6.7%), and in two safety reports the time of drug exposure remained unknown. Twenty safety reports (57.8%) merely reported drug exposure, while 19 (42.2%) also reported pregnancy outcomes, however, without specific maternal toxicities or patterns of birth defects. Spontaneous abortion was reported in eight safety reports without representing a signal of disproportionate reporting compared with either the full database (reporting odds ratio, ROR, 0.06 95% confidence interval, CI 0.03–0.12) or statins (ROR 0.16, 95% CI 0.08–0.32). In conclusion, this study showed that, currently, there are no signals of increased reporting of spontaneous abortion with alirocumab and evolocumab compared with the full database and statins in VigiBase®. Notwithstanding, lack of disproportionality is not synonymous with safety and, as disproportionality analyses depend on the number of safety reports that progressively accumulate in VigiBase®, they should be repeated at regular intervals to confirm the results of the present study.

中文翻译：

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妊娠期抑制 PCSK9 的单克隆抗体的安全性：VigiBase® 中的不成比例性分析

关于妊娠期使用抑制原蛋白转化酶枯草杆菌蛋白酶/kexin 9 型单克隆抗体的安全性数据很少。本研究查询了世界卫生组织全球药物警戒数据库 VigiBase®，以寻找 alirocumab 和 evolocumab 妊娠结局报告不成比例的信号。截至 2023 年 11 月 22 日，已有 45 份关于 evolocumab 暴露的安全报告（氮= 31) 和 alirocumab (氮= 14) 怀孕期间。其中大部分源自欧洲（氮= 25, 55.6%）并且由医疗保健专业人员更频繁地报告（氮= 35, 77.8%）。患者中位年龄为 37 岁（第 25-75 个百分位数；32-41 岁）。在 36 份（80.0%）安全报告中，药物暴露发生在怀孕期间，其中 4 份（8.9%）在怀孕期间通过父亲暴露，3 份（6.7%）在哺乳期间发生药物暴露​​，在 2 份安全报告中，药物暴露时间仍不清楚。 20 份安全报告 (57.8%) 仅报告了药物暴露，而 19 份 (42.2%) 还报告了妊娠结局，但没有具体的母体毒性或出生缺陷模式。八份安全报告中报告了自然流产，与完整数据库（报告比值比，ROR，0.06 95% 置信区间，CI 0.03–0.12）或他汀类药物（ROR 0.16，95% CI 0.08–）相比，不代表报告不成比例的信号。 0.32）。总之，本研究表明，目前，与 VigiBase® 的完整数据库和他汀类药物相比，alirocumab 和 evolocumab 的自然流产报告没有增加。尽管如此，缺乏不成比例性并不意味着安全性，并且由于不成比例性分析取决于 VigiBase® 中逐渐积累的安全性报告的数量，因此应定期重复这些报告以确认本研究的结果。