Eculizumab is a recombinant humanised monoclonal IgG antibody which inhibits terminal complement activation through binding to the human C5 complement protein. It is licensed for use in patients with paroxysmal nocturnal haemoglobinuria (PNH) and atypical haemolytic-uraemic syndrome (aHUS).
The published data currently consist of 18 case reports and five case series which collectively describe at least 119 unique eculizumab-exposed pregnancies. There is currently only one published case of major congenital malformation among 109 infants born following maternal eculizumab use in the first trimester, however the malformation was attributed to concomitant first trimester warfarin exposure. Preterm delivery and, as a consequence, related anomalies and low infant birth weight have been described in a number of the pregnancies resulting in live birth. However, several of these pregnancies were intentionally delivered early in the medical management of various associated maternal medical conditions. As these data are uncontrolled, it is not possible to evaluate whether treatment with eculizumab impacts on these outcomes. A small number of pregnancies ending in spontaneous abortion and intrauterine death have been reported, as has one intrauterine-exposed infant with neurodevelopmental impairment (speech delay) and another infant with childhood cancer (neuroblastoma).
Both aHUS and PNH during pregnancy are associated with an increased risk of rapidly progressive and severe disease, adverse pregnancy outcome and long term maternal morbidity. The available data do not provide any evidence that eculizumab is a structural teratogen, however experience of eculizumab use in pregnancy remains limited and an increased risk of birth defects, although unlikely, can therefore not be excluded. Other adverse or beneficial fetal effects with use in pregnancy remain unquantified, and theorectial concerns regarding compromised neonatal immune function following prenatal exposure should be noted. However, given the potential severity of the maternal conditions for which eculizumab is indicated, a risk-benefit analysis regarding use in pregnancy should be undertaken on a case-by-case basis and treatment should not be withheld purely on account of pregnancy. Patients should however be made aware of the lack of robust fetal safety data, particularly regarding long term outcomes for exposed offspring, and that research is still needed to evaluate pregnancy and maternal outcome with eculizumab therapy versus regimes such as plasma therapy.
Exposure to eculizumab at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy. Heightened maternal and fetal monitoring is advised given the severity of the conditions for which treatment with eculizumab is indicated. However, other factors may 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.
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.