Anti-CGRP migraine biologics linked to higher miscarriage risk

Clinical takeaway: Counsel patients of childbearing potential about the limited pregnancy safety data for anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies, and discuss pregnancy planning before starting therapy. In this study, early pregnancy exposure to these agents was associated with a higher risk of spontaneous abortion (miscarriage), whereas propranolol was not.

Anti-CGRP monoclonal antibodies have transformed migraine prevention and are increasingly used in people of reproductive age. Because CGRP plays a role in implantation, placental development, and uteroplacental blood flow, concerns have persisted about their safety in pregnancy, but human data have been limited.

Researchers analyzed 7,579 singleton pregnancies among 7,119 individuals with pre-existing migraine in the AM-PREGNANT cohort, a large US commercial claims database. Exposures included the anti-CGRP antibodies erenumab, fremanezumab, galcanezumab, and eptinezumab, along with propranolol. Pregnancies were followed through 20 weeks’ gestation for clinically recognized spontaneous abortion.

Among all pregnancies, 1,862 spontaneous abortions occurred. Only 350 pregnancies (4.6%) were exposed to anti-CGRP antibodies, but exposure was associated with a 42% higher risk of spontaneous abortion after adjustment for comorbidities, medication use, and health care utilization. Investigators estimated that by 20 weeks’ gestation, spontaneous abortion would occur in about 28.7% of exposed pregnancies versus 24.5% of unexposed pregnancies, an absolute difference of 4.2 percentage points.

The association held across sensitivity analyses and was modestly attenuated to a 33% higher risk after accounting for possible confounding by migraine severity. In contrast, propranolol was not associated with increased risk.

Important caveats apply. Anti-CGRP antibody users had greater health care utilization and more markers of severe migraine, raising the possibility of residual confounding. Because these agents have long half-lives, about 9 in 10 exposed pregnancies involved treatment that began before conception, and only 9% involved a fill during pregnancy alone.

The authors noted: “Given CGRP’s role in uteroplacental vascular adaptation and placental development, an association with spontaneous abortion is biologically plausible.”

Source: Flatman LK, et al. (2026 Oct 12) JAMA Neurol. Early Pregnancy Use of Anti-CGRP Monoclonal Antibodies and Propranolol and Spontaneous Abortion Risk