Clinical Scorecard: Anti-CGRP antibodies may raise miscarriage risk

At a Glance

Key Highlights

• Among 7,579 pregnancies, 1,862 clinically detected spontaneous abortions occurred by 20 weeks (24.6%).
• Anti-CGRP monoclonal antibody–exposed person-time was associated with a 42% higher adjusted hazard of spontaneous abortion.
• Estimated risk by 20 weeks was 28.7% under a hypothetical scenario of exposure in all pregnancies versus 24.5% without exposure.
• Propranolol exposure was not associated with an increased hazard compared with unexposed person-time, including after bias adjustment.
• The observational design cannot establish causality; residual confounding, limited exposed-pregnancy numbers, and claims-based measurement are important limitations.

Guideline-Based Recommendations

Diagnosis

• The study identified pregestational migraine using diagnostic codes or triptan or ergot prescriptions within 6 months before the last menstrual period.
• Spontaneous abortion was defined as a clinically detected loss at or before 20 weeks, identified through administrative claims.

Management

• The study authors advised clinicians to consider the limited evidence on pregnancy safety when discussing anti-CGRP monoclonal antibody treatment with individuals who may become pregnant.

Monitoring & Follow-up

• The study calls for further research on pregnancy safety, including longer-term offspring outcomes.

Risks

• Anti-CGRP monoclonal antibody exposure was associated with a higher adjusted hazard of spontaneous abortion; the study does not establish that exposure caused the outcome.
• Claims did not directly capture migraine frequency or severity, and prescription claims could not confirm medication administration.
• Very early unrecognized losses may have been missed, gestational age was imputed for many losses, and the commercially insured US population limits generalizability.

Patient & Prescribing Data

The cohort included 7,579 singleton pregnancies among 7,119 patients aged 15 to 45 years with pregestational migraine.

Anti-CGRP exposure included erenumab, fremanezumab, galcanezumab, and eptinezumab. Of pregnancies contributing exposed person-time, 49.1% involved exposure before and during pregnancy, 42% involved pre-pregnancy treatment with residual exposure into gestation, and 8.9% involved exposure during pregnancy only.

Clinical Best Practices

• Discuss the limited pregnancy-safety evidence for anti-CGRP monoclonal antibodies with individuals who may become pregnant, as advised by the study authors.
• When interpreting the reported association, account for possible residual confounding by migraine severity and the observational, claims-based study design.
• Recognize that long half-lives may allow anti-CGRP monoclonal antibody exposure to persist after treatment discontinuation.

Related Resources & Content

• JAMA Neurology study described in the source article