Letter to the editor regarding “Safety profile of erenumab,galcanezumab and fremanezumab in pregnancy and lactation: Analysis of the WHO pharmacovigilance database”

To the Editor,

We read with interest the article by Noseda et. al. titled Safety profile of erenumab, galcanezumab and fremanezumab in pregnancy and lactation: Analysis of the WHO pharmacovigilance database (1). In their analysis of fetal malformations that occurred while the mother was taking a monoclonal antibody targeting the calcitonin gene-related peptide (CGRP) pathway, the authors discuss a case of renal agenesis that occurred concurrent with maternal use of fremanezumab. The authors list the concomitant medications used by the mother, including the anti-migraine preparation acetylsalicylic acid/caffeine/paracetamol, and state that none of these medications are known to be associated with an increased risk of birth defects. In support of this assertion, they reference a 2012 publication by Hernandez et al. (2). Since the time of that publication, however, a significant amount of data associating non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin with fetal renal toxicity has come to light (3,4). In fact, several NSAIDs already include a labeled warning against use in pregnancy due to risk of renal toxicity (5,6). Furthermore, in October 2020, the US Food and Drug Administration issued a requirement to update the labels of all NSAID-containing medications with the risk of severe fetal renal disease with maternal use after 20 weeks’ gestation (3).

In light of these data, we feel that if the event discussed in the article was indeed due to an adverse drug reaction, the aspirin-based preparation cannot be ruled out as a causal agent. Throughout pre-clinical and clinical studies with fremanezumab, no safety signals have been detected with regard to pregnancy or offspring (7). Teva and other CGRP pathway-targeting antibody manufacturers are conducting post-marketing studies to further evaluate this aspect of the safety profile. In the meantime, the prescribing information for fremanezumab has a section dedicated to pregnancy and lactation that summarizes what is currently known and not known. We hereby provide the above clarifications to the editor for consideration in reviewing and commenting on articles on this topic.