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Exposure to anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) medicines in early pregnancy was associated with an increased risk of early pregnancy loss, a study has found.
Publishing their findings in JAMA Neurology on 12 October 2026, researchers analysed data from 7,579 pregnancies among women with pregestational migraine, between 2018 and 2021, from the American Pregnancy Mother-Child cohort (AM-PREGNANT).
“Safety concerns during pregnancy stem from CGRP’s role in vascular regulation, implantation, placental development and uteroplacental blood flow,” the study authors noted.
Researchers followed outcomes up to the 20th week of pregnancy, while outcomes were compared between women taking CGRP receptor antagonists (e.g. erenumab, fremanezumab, galcanezumab and eptinezumab) and those taking propranolol.
Exposure to anti-CGRP mAb medicines in early pregnancy was associated with an increased risk of spontaneous abortion when compared with propranolol usage, which was not, the study results revealed.
The study results also highlighted that of the 7,579 pregnancies, one-quarter (24.6%, n=1,862) were spontaneous abortions during the study period. Of these, more than one-quarter (28.6% n=100) were spontaneous abortions during anti-CGRP mAb-exposed person-time, which was compared with more than one in ten (12.8%, n=37) occurrences among propranolol-exposed person-time without anti-CGRP mAbs, they showed.
After adjustment, the estimated absolute increase in risk associated with anti-CGRP mAb exposure was 4.2 percentage points, the authors said.
However, they noted: “Anti-CGRP mAb users had greater healthcare utilisation, depression and concomitant medication use, suggesting greater disease burden and treatment complexity.”
“[The findings] support further evaluation of anti-CGRP mAb safety and emphasise counselling for individuals of childbearing potential,” the study authors continued.
Commenting on the paper, Mathew Garrod, lead pharmacist for neurosciences and specialist pharmacist in migraine at University Hospital Southampton NHS Foundation Trust, said: “This observational study demonstrates an association between treatment exposure and an increased risk of miscarriage. However, further investigation is warranted to establish whether there is a causal link.
“Existing guidance already recommends avoiding CGRP mAbs during pregnancy. These latest findings add considerable weight to that recommendation, particularly as previous pregnancy safety data were limited and had not identified a clear safety signal.
“Clinicians should therefore ensure that female patients of childbearing potential are aware of the potential risks associated with exposure during an unplanned pregnancy. This should be discussed before initiating treatment and reinforced during subsequent reviews.
“For patients planning pregnancy, these findings also highlight the importance of discontinuing CGRP mAbs sufficiently far in advance to allow the medication to be eliminated from the body.”
The National Institute for Health and Care Excellence (NICE) recommended fremanezumab (Ajovy; Teva Pharmaceutical Industries) as a first-in-class anti-CGRP mAb for the prevention of chronic migraine in 2020. Fremanezumab is a monthly self-administered injection.
In 2023, the body recommended rimegepant (Vydura; Pfizer), an oral formation. NICE guidance notes: “The summary of product characteristics for rimegepant states that as a precautionary measure, it is preferable to avoid taking rimegepant during pregnancy.”
