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.

Four 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.

No internally-controlled statistical studies have assessed human pregnancy outcomes specifically following certolizumab exposure. Uncontrolled case reports and series describe pregnancy outcome data for approximately 1,400 certolizumab-exposed pregnancies, with more than 1,020 exposed in at least the first trimester. The data overall do not suggest that certolizumab use is associated with rates of miscarriage, congenital malformation, preterm delivery or low infant birth weight beyond those observed in the background population. However, the limitations of the study design prevent robust conclusions from being drawn.

Safety data relating to use of TNFα monoclonal antibodies as a group do not suggest an increased 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. General guidance has been provided from a number of authorities on avoiding/deferring live vaccine use in infants exposed to certolizumab in utero. UKTIS recommend a case-specific risk assessment approach when considering the use of live vaccines following in utero exposure. Discussion with UKTIS is recommended in all cases where use of a live vaccine is being considered in an infant <5 months of age where there has been in utero exposure to certolizumab.

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.