Natalizumab is a recombinant humanised anti-α4-integrin antibody licensed for the treatment of highly active relapsing remitting multiple sclerosis (MS).
Data consisting of approximately 760 natalizumab-exposed pregnancies, including approximately 500 first trimester exposures, do not indicate that natalizumab is a major structural teratogen but are too limited to exclude an increased risk. Current data do not raise concern that natalizumab exposure is associated with higher risks of miscarriage and preterm birth but are insufficient to evaluate risks of stillbirth and small for gestational age (SGA).
Natalizumab does not cross the placenta during the first trimester but is actively transported during the second and third trimesters, and exposure late in pregnancy has been associated with the development of reversible mild-to-moderate anaemia and thrombocytopenia in the neonate. To minimise fetal exposure, UK consensus guidelines from the Association of British Neurologists recommend considering giving the last dose during pregnancy at approximately 34 weeks and restarting soon after birth (within 8-12 weeks of the last dose). The decision to stop or delay a dose of natalizumab should be carefully weighed against the risk of relapse.
Use of natalizumab in non-pregnant patients has been associated with an increased risk of progressive multifocal leukoencephalopathy (PML) as a result of reactivation of the commonly carried dormant Polyomavirus JC. Transmission of the Polyomavirus JC to the fetus may be of concern, although there have been no congenital cases of PML described to date. Due to the limited experience of natalizumab use in pregnancy, data investigating both the risk of PML development amongst pregnant patients and the risk of viral transmission to the fetus is currently unavailable.
There is theoretical concern that immunosuppressant antibodies which actively cross the placenta during pregnancy could result in neonatal/infant immunosuppression and an increased risk of infection. There are currently no data regarding the effect of in utero natalizumab exposure on the neonatal/infant immune system. Guidance from Public Health England (PHE) [issued 2017] specified that live vaccines should not be used until the infant is 6 months old following in utero biologic immunosuppressant exposure.
Where treatment with natalizumab is clinically indicated during pregnancy, close monitoring of maternal neurological function is advised. UK consensus guidelines recommend that routine MR brain imaging and monitoring for PML should continue during pregnancy as required. Should maternal symptoms of PML present during pregnancy, enhanced fetal and neonatal monitoring may also be warranted.
Other risk factors may also be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments. Discussion of individual cases with UKTIS is recommended.
This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to NHS health care professionals who are logged in.
If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.
If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.