Researchers evaluating safety reports on erenumab, galcanezumab, and fremanezumab reported in Cephalalgia that they found no specific maternal toxicities, patterns of severe birth defects, or increased reports of spontaneous abortions, but noted that continuous monitoring was critical for pregnant and breastfeeding patients Meaning is Use this medication. They added that more research is needed before the drugs can be determined to be safe in pregnancy.
The study researchers attempted to further evaluate the safety of erenumab, galcanezumab, and fremanezumab, which were recently approved for the prevention of episodic and chronic migraines. Although these drugs have a particularly long half-life that can expose the fetus in women who become pregnant while using them, the safety data for this population are limited. According to animal studies, the calcitonin gene-related peptide (CGRP) is also involved in the regulation of uteroplacental blood flow and uterine relaxation.
Safety reports on suspected adverse drug reactions involving the three drugs (50 with erenumab, 31 with galcanezumab and 13 with fremanezumab) and pregnancy or breastfeeding were collected at VigiBase from the beginning until December 2019. To conduct a disproportionality analysis, the researchers examined the study during the same period of time, safety reports of all other drugs except the previous 3 were also obtained from this database for women between the ages of 14 and 46.
The study researchers carried out a case-by-case assessment of the reported adverse drug reactions (ADRs) and the simultaneously reported drugs and assessed their association with the occurrence of ADRs and whether the diseases prescribed for them were per se risk factors for complications during pregnancy and lactation .
Exposure to erenumab, galcanezumab or fremanezumab occurred in 5 safety reports before pregnancy, 85 reports during pregnancy, 1 report during lactation, and 1 report for paternal exposure and was unknown in 2 reports with regard to exposure time. 51 safety reports reported 1 drug exposure and 43 reported 47 ADRs affecting either mother or fetus.
The results showed numerous ADRs, including 15 reports of 18 maternal toxicities, 1 report of poor breastfeeding, 23 of spontaneous abortions, 3 of premature births / premature births, and 2 of birth defects. The reported birth defects included 1 case of anencephaly with erenumab and one case of renal aplasia and gastroesophageal reflux disease with fremanezumab. Compared to the full database (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.
The limitations of the study included the limited number of safety reports analyzed, the different mechanisms of the three drugs (which consequently may not have an identical safety profile), and possible dilution or awareness biases due to the potentially high variability of spontaneous reporting in event reporting.
The study researchers concluded: “Due to the relatively limited number of reported ADRs, the lack of long-term safety data, and the lack of reversal strategies for these antibodies and their clinical implications, continuous monitoring is required in pregnant and lactating women exposed to them Drugs. “They added that” more representative database analysis and pharmacoepidemiological studies are needed before determining the safety of erenumab, galcanezumab and fremanezumab in pregnancy. ”
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