A new study presented at the American Headache Society (AHS) Annual Meeting in Florida has found that CGRP monoclonal antibodies—a class of migraine prevention drugs hailed as a 'wonder drug' on the NHS—are associated with a 45% higher risk of miscarriage when used during the first trimester. The research, which analysed 7 ,579 pregnancies in 7,119 women aged 15 to 45 with a pre-pregnancy migraine diagnosis, compared outcomes among those using the injections,those on the beta-blocker propranolol, and those taking no medication. Current NHS guidance already advises that pregnant women or those trying to conceive should not use these drugs, but experts say the new data underscore the need for stronger reproductive safety precautions .

The 45% miscarriage risk figure — and what it compares to

According to the study presented at the AHS meeting, women who took CGRP monoclonal antibodies between eight and 12 weeks of pregnancy experienced a miscarriage rate of 5%, compared to just 2% among those taking propranolol alone. That 45% relative risk increase emerged from a dataset that included over 7,500 pregnancies across the three comparison groups. The drugs—erenumab, galcanezumab, fremanezumab, and eptinezumab—are currently approved in the UK for patients with at least four migraine days per month who have failed three or more other preventive medications. The findings do not question the drugs' efficacy for the general population,but they introduce a critical reproductive safety signal that the source report says warrants a closer look at prescribing practices.

Why the drug's 5-month clearance window complicates pregnancy planning

Professor Vincent Martin, director of the Headache and Facial Pain Center at the University of Cincinnati Gardner Neuroscience , explained to the study's authors that the pharmacokinetics of CGRP monoclonal antibodies pose a unique challenge. 'When you give CGRP therapies by injection, they stay in the body for 5 months, so this is an issue that could come up with a lot of different patients where they have an unexpected pregnancy, or maybe they don't even know that they should be off of therapy for five months before trying to get pregnant,' he said. This prolonged presence means that even if a woman stops treatment upon learning she is pregnant, the drug may still be active during the critical first trimester. The source report highlights that this factor complicates clinical management and underscores the importance of preconception counseling for women of childbearing potential.

What NHS guidance already says — and what this study adds

The NHS has recommended against using CGRP monoclonal antibodies in pregnancy since the drugs were approved in March 2020. However,the source report notes that the new data from the AHS meeting adds statistical weight to that precaution. The investigator of the study, Dr Leah Flatman from the Centre Hospitalier Universitaire Sainte-Justine in Montreal, stated, 'These results support cautious use of anti-CGRP therapies and emphasize the importance of preconception counseling for women of childbearing potential. They also highlight the need for future safety research of pregnancy,including studies of fetal and long-term offspring outcomes.' For the roughly seven million migraine sufferers in the UK—where women are three times more likely to be affected than men—the study reinforces that significant benefits for migraine control must be balanced against potential fetal risks.

The missing data: fetal outcomes and long-term offspring safety

While the study provides the largest analysis to date on early pregnancy exposure to CGRP monoclonal antibodies, it leaves several questions unanswered. the data presented at the AHS meeting only covers miscarriage rates in the first trimester; it does not address potential effects on fetal development throughout the rest of pregnancy or on the health of children after birth. As Dr Flatman acknowledged, 'future safety research of pregnancy, including studies of fetal and long-term offspring outcomes' is needed. Additionally, the source report does not specify how many of the women on CGRP mAbs were using them in line with NHS criteria versus off-label, nor does it detail the time between last injection and conception. Those variables would matter for clinicians trying to assess individual risk.