USE OF USTEKINUMAB IN PREGNANCY

Ustekinumab is a fully human IgG1κ monoclonal antibody to interleukin (IL)-12/23 produced using recombinant DNA technology. Ustekinumab is licensed for the management of plaque psoriasis, psoriatic arthritis, Crohn’s disease and ulcerative colitis.

Some maternal autoimmune/inflammatory conditions are associated with increased risks of adverse pregnancy outcomes, such as miscarriage, preterm delivery and low birth weight. Adequate control of the maternal condition may therefore decrease the risk of such adverse pregnancy outcomes; however, robust data to support this are not available.

Data regarding the fetal safety of ustekinumab use in pregnancy are provided by studies which collectively describe more than 600 exposed pregnancies. However, several of these studies have important methodological limitations which affect the conclusions that can be provided, and the available data do not provide clear evidence that ustekinumab use in pregnancy is causally associated with increased risks of miscarriage, malformation, intrauterine fetal death/stillbirth, preterm delivery, impaired fetal growth or neurodevelopmental impairment. Larger studies utilising advanced analytical methods are required to confirm these findings.

The available data do not provide any signal to indicate that ustekinumab use in pregnancy increases the risk of miscarriage, malformation, intrauterine fetal death, preterm delivery, low birth weight or neurodevelopmental impairment. However, it is not currently feasible to provide a reliable evidence-based evaluation of the risk posed to the fetus due to the small number of exposed pregnancies described in the literature.

As ustekinumab is not expected to cross the placenta during the first trimester, congenital malformations due to a direct effect on the fetus would not be anticipated. Given the available data are methodologically limited, women who have been exposed to ustekinumab in early pregnancy should be particularly encouraged to attend their routine prenatal monitoring scans.

There is theoretical concern that the use of immunosuppressant antibodies that actively cross the placenta during pregnancy (including ustekinumab) could result in immunosuppression in the infant and increased risk of infection. Guidance from the manufacturer specifies that infants exposed to ustekinumab in utero should avoid live vaccines until twelve months following birth, or until ustekinumab infant serum levels are undetectable. Discussion with UKTIS is recommended in cases where there is a high risk of tuberculosis infection in the infant.

Exposure to ustekinumab 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 which could independently increase the risk of adverse pregnancy outcome may be present in individual cases. Such factors are important to consider when performing case-specific risk assessments.