Abstract and Introduction
Objective: To report a case of a woman who continued erenumab for migraine prophylaxis throughout her pregnancy and to review the literature for pregnancy safety data for the calcitonin gene-related peptide (CGRP) receptor and ligand-directed therapies currently approved for migraine prophylaxis in the United States.
Background: Migraine is a common headache disorder that can be significantly disabling. Many people experiencing migraine seek out preventative therapies to improve their quality of life. Unfortunately, currently approved prophylactic agents may not be safe to use during pregnancy, potentially limiting the use of these agents in women of childbearing potential. As the newest class of prophylactic agents for migraine, CGRP agents have limited pregnancy safety data in humans.
Methods: A review of the literature was conducted through the PubMed database using the terms pregnancy and either erenumab, fremanezumab, galcanezumab, eptinezumab, rimegepant, or atogepant. Additional sources of information such as prescribing information, assessment reports submitted to the European Medicines Agency (EMA), and manufacturer data were sought.
Results: One case report was found in the literature documenting a human pregnancy with no adverse effects in the baby after exposure to erenumab. However, the last dose was administered in the second week of pregnancy and discontinued thereafter. The evaluation of 92 safety reports describing maternal exposure prior to or during pregnancy to either erenumab, galcanezumab, or fremanezumab was located. Incidence of miscarriage and congenital anomalies appear to be similar to rates in the general population.
Conclusions: The use of erenumab during pregnancy in our patient resulted in no known harm to the child. This case is unique in that the mother continued to receive erenumab throughout the pregnancy. Safety data is lacking regarding the use of these agents during pregnancy, despite their frequent use in women of childbearing potential.
In our current pharmacologic armamentarium, there are many medications that are approved by the US Food and Drug Administration (FDA) for migraine prophylaxis or that are commonly used off label for this indication. However, valproates, topiramate, carbamazepine, oxcarbazepine, phenytoin, and amitriptyline should be avoided in pregnant women due to their potential for teratogenicity.[1–8] Gabapentin, lamotrigine, levetiracetam, zonisamide, metoprolol, propranolol, and onabotulinumtoxinA should only be used in pregnant women if the potential benefits outweigh the risks due to the potential for fetal harm in animal studies.[9–16] Pregnancy information is limited with calcitonin gene-related peptide (CGRP) receptor or ligand-directed therapies. Unintended and intended pregnancies are likely to occur in clinical practice because a significant portion of patients seeking these prophylactic agents are women of childbearing potential (Table 1).
CGRP receptors are involved with blood vessel vasodilation, neurogenic inflammation, and pain sensation signaling. Intravenous infusion of CGRP in people with migraine provokes migraine-like symptoms, which may suggest a causal role. CGRP receptors found on osteoclasts, osteoblasts, and placental tissue may be relevant to potential adverse fetal effects.[25,26] CGRP levels normally fluctuate during human pregnancy and may play a key role in utero-placental functions, including cellular differentiation, proliferation, hormone signaling, and uteroplacental blood flow regulation. It is currently unknown if continuing a CGRP antagonist during pregnancy would negatively affect crucial fetal developments or embryonic skeletal growth.
In humans, the transfer of immunoglobulin G (IgG) antibodies across the placenta is limited before the 16th week of gestation and increases after the 22nd week. Maternal-fetal transfer of IgG antibodies is dependent on active transport via syncytiotrophoblast cells in the placenta; these cells do not appear until after 20 to 22 weeks of pregnancy. Rituximab and infliximab are examples of IgG monoclonal antibody agents that have been used in pregnant women when clinically necessary. The placental transfer of rituximab and infliximab is negligible during the first trimester and increased in the late second and third trimesters.[29,30] If treatment is warranted in a pregnant patient with these agents, completing treatment in the first trimester is preferred.
Given the paucity of pregnancy safety information for this new class of medication, this review aims to summarize the current knowledge in the literature and add a case report of a woman with known exposure to erenumab throughout her pregnancy with no adverse outcomes.
Headache. 2022;62(10):1256-1263. © 2022 Blackwell Publishing