Researchers who evaluated safety reports on erenumab, galcanezumab, and fremanezumab reported in Cephalalgia that they did not find specific maternal toxicities, patterns of major birth defects, or increased reporting of spontaneous abortion, but noted that continuous surveillance is critical for pregnant and lactating patients who use these drugs. They added that more research is needed before determining the drugs’ safety in pregnancy.

Study researchers sought to further evaluate the safety of erenumab, galcanezumab, and fremanezumab, which were recently approved for the prevention of episodic and chronic migraine. Although these drugs have a particularly long half-life that could result in fetal exposure in women who become pregnant while using them, they are limited in safety data for this population. Calcitonin gene-related peptide (CGRP) is also involved in regulating utero-placental blood flow and uterine relaxation, according to animal studies.

Safety reports of suspected adverse drug reactions involving the 3 drugs (50 associated with erenumab, 31 with galcanezumab, and 13 with fremanezumab) and pregnancy or lactation were collected from VigiBase from the database’s inception through December 2019. To perform a disproportionality analysis, study researchers also retrieved safety reports of all other drugs, excluding the previous 3, from this database over the same period for females aged between 14 and 46 years.

Study researchers conducted a case-by-case assessment of the reported adverse drug reactions (ADRs) and the co-reported drugs, evaluating their association with ADR onset and whether the diseases for which they were prescribed were per se risk factors for complications during pregnancy and lactation.


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Exposure to erenumab, galcanezumab, or fremanezumab occurred before pregnancy in 5 safety reports, during pregnancy in 85 reports, during lactation in 1 report, via paternal exposure in 1 report, and was unknown regarding exposure time in 2 reports. 51 safety reports reported 1 drug exposure, and 43 reported 47 ADRs affecting either mother or fetus.

Findings indicated numerous ADRs, including 15 reports of 18 maternal toxicities, 1 report of poor breastfeeding, 23 of spontaneous abortions, 3 of pre-term birth/premature birth, and 2 of birth defects. The birth defects reported included 1 case of anencephaly with erenumab and one case of renal aplasia and gastroesophageal reflux disease with fremanezumab. Compared with the full database (reporting odds ratio 1.46, 95% CI 0.97-2.20), there was no indication of disproportionate reporting for spontaneous abortion with erenumab, galcanezumab, or fremanezumab.

Limitations of the study included the limited number of safety reports analyzed, the different mechanisms of the 3 drugs (which consequently may not share an identical safety profile), and possible dilution or notoriety bias due to the potentially high event reporting variability of spontaneous reporting.

The study researchers concluded, “Because of the relatively limited number of ADRs reported, the lack of long-term safety data and the lack of reversal strategies for these antibodies and their clinical effects, continuous surveillance is required in pregnant and lactating women exposed to these drugs.” They added that “more representative database analyses and pharmacoepidemiological studies are warranted prior to determining erenumab, galcanezumab, and fremanezumab safety in pregnancy.”

Reference

Noseda R, Bedussi F, Gobbi C, Zecca C, Ceschi A. Safety profile of erenumab, galcanezumab and fremanezumab in pregnancy and lactation: Analysis of the WHO pharmacovigilance database. Cephalalgia. Published online January 12, 2021. doi:10.1177/0333102420983292