Early Pregnancy Exposure to Anti-CGRP Monoclonal Antibodies Linked to Higher Spontaneous Abortion Risk
KEY TAKEAWAYS
- Exposure to anti-CGRP monoclonal antibodies in early pregnancy was associated with a 42% higher adjusted risk of spontaneous abortion among individuals with migraine.
- Propranolol exposure was not associated with an increased risk of spontaneous abortion.
- According to the authors, the findings support consideration of the limited pregnancy safety data for anti-CGRP therapies when counseling individuals who may become pregnant.
Exposure to calcitonin gene-related peptide (CGRP) monoclonal antibodies during early pregnancy was associated with a higher risk of spontaneous abortion (ie, unexpected loss of pregnancy before 20 weeks) among individuals with migraine, according to findings from a retrospective cohort study published in JAMA Neurology. In contrast, researchers found no increased risk associated with propranolol exposure during early pregnancy.
The study included 7579 singleton pregnancies among 7119 individuals aged 15 to 45 years with pregestational migraine identified in the AM-PREGNANT cohort, which was derived from a US commercial insurance claims database. Participants were followed through 20 weeks’ gestation. Anti-CGRP monoclonal antibody exposure included Aimovig (erenumab; Novartis, Basel, Switzerland; Amgen, Thousand Oaks, CA), Ajovy (fremanezumab; Teva Pharmaceuticals, Parsippany, NJ), Emgality (galcanezumab; Eli Lilly and Company, Indianapolis, IN), or Vyepti (eptinezumab; Deerfield, IL) and was modeled as a time-varying exposure.
Key results included the following:
- Anti-CGRP monoclonal antibody exposure was associated with a higher risk of spontaneous abortion compared with unexposed person-time (adjusted hazard ratio [aHR], 1.42; 95% CI, 1.12 to 1.80).
- A probabilistic analysis accounting for potential residual confounding by migraine severity produced a similar association (HR, 1.33; 95% simulation interval, 1.23 to 1.45).
- Propranolol exposure was not associated with spontaneous abortion (aHR, 1.02; 95% CI, 0.71 to 1.47).
- In a standardized analysis, the estimated risk of spontaneous abortion by 20 weeks was 28.7% under hypothetical anti-CGRP monoclonal antibody exposure compared with 24.5% without exposure, an adjusted difference of 4.2 percentage points.
Practical Implications in the Clinic
These findings add human pregnancy data relevant to discussions about migraine prevention in individuals of childbearing potential. They do not establish a causal relationship but reinforce the need to consider pregnancy plans and the limited safety evidence surrounding anti-CGRP monoclonal antibody therapy when making treatment decisions.
The investigators noted several limitations, including possible residual confounding because individuals receiving anti-CGRP monoclonal antibodies had markers of greater migraine severity and treatment complexity. The claims-based analysis also could not capture very early pregnancy losses and included data only through 2021, when the number of pregnancies exposed to these relatively new therapies was limited.
Source
Flatman LK, Leal LF, Leroux E, Lipton RB, Bérard A. Early Pregnancy Use of Anti-CGRP Monoclonal Antibodies and Propranolol and Spontaneous Abortion Risk. JAMA Neurol. Published online October 12, 2026. doi:10.1001/jamaneurol.2026.3573