USE OF CERTOLIZUMAB IN PREGNANCY

Certolizumab is a PEGylated Fab’ fragment of a humanised monoclonal antibody that inhibits tumour necrosis factor alpha (TNFα) and is licensed to treat rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis and plaque psoriasis.

Three studies have demonstrated minimal placental transfer of certolizumab in human pregnancy. As placental function begins at around 10 to 12 weeks, it is considered likely that direct fetal exposure as a consequence of maternal certolizumab use beyond this time would be minimal. However, as there is no active placental barrier in the early stages of fetal development, a theoretical teratogenic/embryotoxic risk is possible.

Human pregnancy exposure and outcome data consist of 11 uncontrolled descriptive studies which collectively report more than 560 exposed pregnancies, with more than 360 exposed in at least the first trimester. Due to methodological limitations and small-to-moderate study sample sizes, robust conclusions regarding the risk of adverse fetal effects cannot be drawn. However, the available data do not suggest that certolizumab is associated with an increased risk of miscarriage or congenital malformation. Although cases of intrauterine fetal death, preterm delivery and low birth weight have been described in uncontrolled studies, the available data are potentially biased and confounded. As such, it is not possible to confirm an association exists between gestational certolizumab exposure and these outcomes. No studies were located which investigated risks of neurodevelopmental impairment or childhood cancer.

Although safety data relating to the use of certolizumab in pregnancy are limited, additional data describing maternal exposure to TNFα monoclonal antibodies as a group are available. Data provided from a meta-analysis do not suggest that maternal anti-TNFα use in pregnancy increases the risk of adverse pregnancy or fetal outcomes.

There are theoretical concerns that the use of immunosuppressant antibodies, which actively cross the placenta, may result in neonatal or infant immunosuppression and increase the risk of infection. Given that certolizumab is minimally transferred across the placenta, it is unlikely that infants born to women who used certolizumab in pregnancy would experience sufficient levels of TNFα inhibition to significantly inhibit their immune response. However, the manufacturer advises that, unless the benefit of the vaccination clearly outweighs the theoretical risk, live or live-attenuated vaccines should only be administered to infants five months after the last maternal administration occurred during pregnancy.

Exposure to certolizumab at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy or any additional fetal monitoring. However, other risk 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.