How safe is ustekinumab before, during and after pregnancy in IBD?

Review by Prof. Edyta Tulewicz-Marti (Poland)

Study Summary 

The major concept we should keep in mind in women of reproductive age with IBD who are undergoing advanced treatment of the disease is the possibility of pregnancy and the influence of that treatment on the fetus. Treatment regimens using ustekinumab (USTK) had been demonstrated as having no increased risk of an adverse pregnancy outcome (including congenital malformation), yet the exact influence of this medication on the postnatal period was not clear and accurate data were lacking. In the study by Julsgaard et al., pregnant women with IBD were prospectively recruited from 19 hospitals in Denmark and the Netherlands between 2018 and 2022, and infant infections leading to hospitalization and/or antibiotics and developmental milestones assessed.¹ According to the results, in 78 live-born infants from 76 pregnancies, the risk of adverse pregnancy outcomes was low and developmental milestones unaffected. At birth, the median infant cord blood and maternal blood ustekinumab levels were 3.0 and 1.4 µg/mL, respectively. The longer the interval between last exposure and assay, the lower the level. By six months 74% of the infants had undetectable levels of USTK and the men time to infant clearance of USTK was 6.7 months (95% confidence interval, 6.1-7.3 months). Moreover, infant ustekinumab concentration at birth was not associated with a risk of infections ad of the infections that occurred in these infants all but one resolved without sequalae.

Commentary 

Among patients and some physicians there are many incorrect beliefs regarding the use of biologics during pregnancy; medical counselling is, therefore, extremely important. On the one hand, it is known that active inflammation in IBD is associated with an increased risk of adverse pregnancy outcomes, while on the other, treatments must be safe for both the woman and the fetus. Even though most conventional drugs used in IBD (except for methotrexate) are considered low risk during conception and pregnancy, for newer medications, evidence is still limited.² IBD drugs cross the placenta either by passive transfer [small molecules] or by active transport [biologics]; thus, fetuses are exposed to the drugs while the mother is receiving them during pregnancy.³ The data from the study performed by Julsgaard et al. are the largest of their kind to date and provide the foundation for counseling and treating pregnant women who require ustekinumab therapy during pregnancy. This was a prospective study and showed that ustekinumab was safe during pregnancy and in fertile women who may get pregnant. In their discussion they also note that breastfeeding did not affect ustekinumab clearance and there was no significant ustekinumab transfer via breast milk, indicating that breastfeeding was safe. Moreover, by knowing the ustekinumab clearance profile, it seems that live attenuated vaccinations from six months of age are of low risk. In terms of the limitations of the study, while it would have been valuable to have longitudinal data on USTK levels over time in these infants it may have been ethically difficult to justify testing at more frequent intervals. More data and longer-term data are needed on the safety of USTK.

Citations

1. Julsgaard M, Wieringa JW, Baunwall SMD, et al. Infant Ustekinumab Clearance, Risk of Infection, and Development After Exposure During Pregnancy. Clin Gastroenterol Hepatol. 2025; 23:134-143.
2. Sousa P, Gisbert JP, Julsgaard M, et al. Navigating Reproductive Care in Patients with Inflammatory Bowel Disease: A Comprehensive Review. J Crohns Colitis. 2024;18(Supplement_2): ii16-ii30
3. Torres J, Chaparro M, Julsgaard M, et al. European Crohn’s and Colitis guidelines on sexuality, fertility, pregnancy, and lactation. J Crohns Colitis 2023; 17:1–27

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