Division of Clinical Pharmacology and Toxicology, Institute of Pharmacological Sciences of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano, Switzerland.
Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano, Switzerland.
Cephalalgia. 2021 Jun;41(7):789-798. doi: 10.1177/0333102420983292. Epub 2021 Jan 12.
To assess the safety profile of erenumab, galcanezumab and fremanezumab in pregnancy and lactation.
Safety reports of suspected adverse drug reactions were retrieved from VigiBase as of 31 December 2019, for a case-by-case assessment and disproportionality analysis using the reporting odds ratio (ROR).
There were 94 safety reports: 50 (53.2%) on erenumab, 31 (33.0%) on galcanezumab, and 13 (13.8%) on fremanezumab. In five (5.3%) safety reports, drug exposure occurred prior to pregnancy, in 85 (90.4%) during pregnancy, in one (1.1%) during lactation, in one (1.1%) via paternal exposure, and in two (2.1%) the exposure time was unknown. Out of 94 safety reports, 51 (54.3%) consisted only of drug exposure, while 43 (45.7%) additionally reported 47 adverse drug reactions including maternal toxicities (n = 18), poor breastfeeding (n = 1), spontaneous abortion (n = 23), preterm birth/prematurity (n = 3), and birth defects (n = 2). There was no signal of disproportionate reporting for spontaneous abortion compared to the full database (reporting odds ratio 1.46, 95% confidence interval 0.97-2.20). When triptans were used as a comparator group, a signal of disproportionate reporting for spontaneous abortion was detected in association with erenumab, galcanezumab, and fremanezumab (reporting odds ratio 1.86, 95% confidence interval 1.12-3.13), which was not statistically significant after excluding confounded safety reports (reporting odds ratio 1.21, 95% confidence interval 0.67-2.21).
No specific maternal toxicities, patterns of major birth defects, or increased reporting of spontaneous abortion were found. However, because of the relatively limited number of adverse drug reactions reported and the lack of long-term safety data, continuous surveillance is required in pregnant and lactating women exposed to these drugs.
评估依那西普、加兰他敏和弗雷美尼布在妊娠和哺乳期的安全性概况。
截至 2019 年 12 月 31 日，从 VigiBase 中检索疑似药物不良反应的安全性报告，进行病例评估和比例失调分析，使用报告比值比（ROR）。
共有 94 份安全性报告：50 份（53.2%）涉及依那西普，31 份（33.0%）涉及加兰他敏，13 份（13.8%）涉及弗雷美尼布。在 5 份（5.3%）安全性报告中，药物暴露发生在妊娠前，85 份（90.4%）在妊娠期间，1 份（1.1%）在哺乳期，1 份（1.1%）通过父方暴露，2 份（2.1%）暴露时间未知。在 94 份安全性报告中，51 份（54.3%）仅报告药物暴露，而另外 43 份（45.7%）还报告了 47 种药物不良反应，包括母体毒性（n=18）、母乳喂养不良（n=1）、自然流产（n=23）、早产/早产（n=3）和出生缺陷（n=2）。与整个数据库相比，自然流产的报告比例没有显示不成比例（报告比值比 1.46，95%置信区间 0.97-2.20）。当曲坦类药物作为对照组时，发现依那西普、加兰他敏和弗雷美尼布与自然流产的报告比例不成比例（报告比值比 1.86，95%置信区间 1.12-3.13），但在排除混杂的安全性报告后，这一结果并不具有统计学意义（报告比值比 1.21，95%置信区间 0.67-2.21）。
未发现特定的母体毒性、主要出生缺陷模式或自然流产报告增加。然而，由于报告的药物不良反应数量相对较少，以及缺乏长期安全性数据，因此需要对暴露于这些药物的孕妇和哺乳期妇女进行持续监测。
