Anti-CGRP Antibody Exposure Near Conception Linked to Miscarriage Risk

Exposure to anticalcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) around conception and in early pregnancy was associated with a higher risk of spontaneous abortion among individuals with migraine, while propranolol was not, according to a retrospective cohort study published online in JAMA Neurology.¹

Migraine disproportionately affects people of reproductive age, and CGRP pathway therapies have transformed prevention since 2018.^2,3 CGRP also plays a role in implantation and placental development, and guidelines recommend stopping anti-CGRP mAbs 5 to 6 months before conception.¹ Evidence on early pregnancy safety remains limited.

Anti-CGRP mAb Exposure Tied to Higher Spontaneous Abortion Risk

Researchers analyzed 7579 singleton pregnancies among 7119 individuals with pregestational migraine using the AM-PREGNANT cohort, derived from the Merative MarketScan Commercial Database. Pregnancies had last menstrual periods on or after November 1, 2018, and were followed through 20 weeks' gestation. Overall, 1862 pregnancies (24.6%) ended in spontaneous abortion.

Compared with time unexposed to either drug, anti-CGRP mAb exposure was associated with an adjusted hazard ratio (aHR) of 1.42 (95% CI, 1.12-1.80). Propranolol, included as a commonly used migraine preventive to provide context, showed no association (aHR, 1.02; 95% CI, 0.71-1.47).

Anti-CGRP mAb-exposed person-time, contributed by 350 pregnancies, included 100 spontaneous abortions (28.6%, unadjusted). Under a modeled scenario in which all pregnancies were exposed to anti-CGRP mAbs, the adjusted risk by 20 weeks would be 28.7%, compared with 24.5% under no exposure. This corresponds to an adjusted risk difference of 4.2 percentage points.

Because of the long half-lives of these agents, dosing before pregnancy carried residual drug into pregnancy. Exposure was counted for 135 to 155 days after each dose or infusion. Among the 350 exposed pregnancies, 172 (49.1%) had exposure before and during pregnancy, 147 (42%) before pregnancy only, and 31 (8.9%) during pregnancy only.

Could Migraine Severity Explain the Association?

Patients using anti-CGRP mAbs had greater health care use before pregnancy and more markers of severe migraine, including higher rates of triptan, nonsteroidal anti-inflammatory drug, and ondansetron use, as well as more depression. A probabilistic bias analysis using chronic migraine as a proxy for severity modestly attenuated the association (bias-adjusted hazard ratio, 1.33; 95% simulation interval, 1.23-1.45). Estimates were also similar when exposure was defined using 3 to 6 drug half-lives (aHR range, 1.38-1.50).

Claims Data Cannot Capture Migraine Severity

The authors cautioned that claims data do not capture migraine frequency or severity, so residual confounding by indication remains possible. Pregnancy intention was also unavailable. Anti-CGRP mAb exposure in early pregnancy may reflect an unplanned pregnancy or residual drug around conception, whereas propranolol may be continued intentionally when clinically indicated.

The authors also noted that outcome timing was partly imputed. Among the 1862 spontaneous abortions, 1097 (58.9%) had no gestational age code and were assigned an 8-week gestational age to estimate the last menstrual period, and very early losses that were not clinically detected were likely missed. Findings may not generalize beyond commercially insured populations, and data ended in 2021, which limited the number of exposed pregnancies and statistical precision.

Counseling Patients Who May Become Pregnant

The authors concluded that the findings support further evaluation of anti-CGRP mAb safety during pregnancy.

“Given the increasing use of anti-CGRP mAbs for migraine prevention among individuals of reproductive age, further research is needed to evaluate their safety during pregnancy, including studies examining spontaneous abortion, fetal outcomes, and longer-term offspring outcomes,” they wrote. “Until more evidence is available, clinicians should consider the limited evidence on pregnancy safety when discussing anti-CGRP mAb treatment with individuals who may become pregnant.”

The study was funded by the Canadian Foundation for Innovation, which had no role in its design or conduct. Two coauthors disclosed personal fees from pharmaceutical companies, including AbbVie, Teva, and Pfizer.

References

1. 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
2. Cohen F, Brooks CV, Sun D, et al. Prevalence and burden of migraine in the United States: a systematic review. Headache. 2024;64(5):516-532. doi:10.1111/head.14709
3. Steiner TJ, Stovner LJ, Jensen R, Uluduz D, Katsarava Z; Lifting The Burden: the Global Campaign against Headache. Migraine remains second among the world’s causes of disability, and first among young women: findings from GBD2019. J Headache Pain. 2020;21(1):137. doi:10.1186/s10194-020-01208-0