Early Pregnancy Use of Anti-CGRP Monoclonal Antibodies and Propranolol and Spontaneous Abortion Risk

Abstract

Importance Migraine affects individuals of reproductive age, but treatment options during pregnancy are limited due to safety concerns. Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) are effective for migraine prevention; however, CGRP is important in placental development. Objective To determine whether early pregnancy exposure to anti-CGRP mAbs or propranolol is associated with spontaneous abortion compared with no exposure. Design, Setting, and Participants This retrospective cohort study used data from the AM-PREGNANT cohort, derived from the Merative MarketScan Commercial Database, from 2018 to 2021. Participants were followed up through 20 weeks’ gestation or until spontaneous abortion or censoring. Among 7 991 200 pregnancies identified in the AM-PREGNANT cohort, 7119 individuals contributing 7579 singleton pregnancies met the predefined eligibility criteria, including age 15 to 45 years, continuous insurance enrollment, last menstrual period (LMP) on or after November 1, 2018, pregnancy end or 20-week censoring by December 31, 2021, and pregestational migraine, defined as a migraine diagnosis or triptan or ergot prescription within 6 months before LMP. Data were analyzed in early 2026. Exposures Anti-CGRP mAbs (erenumab, fremanezumab, galcanezumab, eptinezumab) or propranolol, defined as 1 or more filled prescription or injection procedure claim during follow-up and modeled as time-varying. Main Outcome and Measures Spontaneous abortion occurring at 20 weeks’ or less gestation. Multivariable Cox proportional hazards models adjusted for comorbidities and concomitant medications estimated the risk of spontaneous abortion. Results Among 7579 pregnancies in 7119 individuals (mean [SD] age, 31.6 [5.5] years), 1862 spontaneous abortions occurred. There were 100 spontaneous abortions (28.6%) during anti-CGRP mAb-exposed person-time, compared with 37 events among propranolol-exposed person-time without anti-CGRP mAbs (12.8%). Compared with unexposed individuals, anti-CGRP mAbs exposure was associated with an increased risk of spontaneous abortion (adjusted hazard ratio [aHR], 1.42; 95% CI, 1.12-1.80), which remained similar in bias-adjusted analyses (HR, 1.33; 95% simulation interval [SI], 1.23-1.45). Propranolol exposure was not associated with increased risk (aHR, 1.02; 95% CI, 0.71-1.47; bias-adjusted HR, 1.00; 95% SI, 0.96-1.03). Conclusion and Relevance In this study, early pregnancy exposure to anti-CGRP mAb was associated with a higher risk of spontaneous abortion, while no association was observed with propranolol. These findings support further evaluation of anti-CGRP mAb safety and emphasize counseling for individuals of childbearing potential.