USE OF SMALL-MOLECULE CGRP RECEPTOR ANTAGONISTS IN PREGNANCY

Small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists, also known as gepants, are used in the prevention and acute treatment of migraine. This class includes atogepant, rimegepant, ubrogepant and zavegepant; however, only atogepant and rimegepant are currently licensed for use in the UK.

Human pregnancy exposure data for gepants are extremely limited. Available evidence consists of a small case series, two disproportionality analyses of spontaneous pharmacovigilance reports, and interim results from a cohort study that included 119 rimegepant-exposed pregnancies, of which 47 were exposed during the first trimester. These data are insufficient in both quantity and quality to permit an evidence-based assessment of fetal risk. Although no signal has emerged to suggest that gepants are major human teratogens, evidence with substantial methodological limitations has raised a potential signal for an association with miscarriage. However, the available evidence is insufficient to determine whether this represents a causal association, and further investigation is required.

Migraine is common in women of reproductive age and may occur in pregnancy. It has been estimated that in up to 80% of women who experience migraine, both the frequency and severity of attacks improve during the second and third trimesters of pregnancy; thus, routine prophylaxis is not recommended during pregnancy.  However, in some cases, migraine may fail to improve or may even worsen. In some women, migraine presents for the first time during pregnancy.

Migraine itself does not appear to increase the risk of miscarriage, congenital malformations, or other pregnancy complications. However, if migraine attacks are frequent or severe and left untreated, subsequent maternal effects such as dehydration, inadequate nutrition, and stress may have an adverse effect on the fetus.

If appropriate, non-pharmacological measures, including identification and avoidance of trigger factors, should be tried before drug therapy is considered. Medication may be required for headaches that are severe or associated with nausea and vomiting, and adequate fluid replacement should be provided where dehydration is present. Established treatments such as paracetamol and, where clinically indicated, sumatriptan are generally preferred during pregnancy (see Treatment of Migraine in Pregnancy monograph for more details). Given the paucity of pregnancy safety data, gepants should generally be reserved for situations in which the potential benefit is considered to outweigh the uncertainties regarding fetal risk.

Exposure to gepants at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy. However, other risk factors which could independently increase the risk of adverse pregnancy outcome may be present in individual cases. Such factors are important to consider when performing case-specific risk assessments. Given the limited pregnancy data available for this class of drug, an additional early anomaly scan around 16 weeks of pregnancy could be considered following first-trimester exposure. UKTIS welcomes reports of gepant exposure during pregnancy.