Safety profile of erenumab, galcanezumab and fremanezumab in pregnancy and lactation: Analysis of the WHO pharmacovigilance database

Cephalalgia. 2021 Jun;41(7):789-798. doi: 10.1177/0333102420983292. Epub 2021 Jan 12.

Abstract

Objective: To assess the safety profile of erenumab, galcanezumab and fremanezumab in pregnancy and lactation.

Methods: 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).

Results: 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).

Conclusions: 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.

Keywords: Calcitonin gene-related peptide; VigiBase; adverse drug reaction; migraine.

MeSH terms

  • Abortion, Spontaneous
  • Adverse Drug Reaction Reporting Systems
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Breast Feeding*
  • Calcitonin Gene-Related Peptide Receptor Antagonists / administration & dosage
  • Calcitonin Gene-Related Peptide Receptor Antagonists / adverse effects*
  • Databases, Factual
  • Drug-Related Side Effects and Adverse Reactions*
  • Female
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / adverse effects*
  • Infant, Newborn
  • Lactation / drug effects*
  • Male
  • Pharmacovigilance
  • Pregnancy
  • Premature Birth
  • World Health Organization

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Immunologic Factors
  • fremanezumab
  • galcanezumab
  • erenumab