Ustekinumab Levels in Pregnant Women With Inflammatory Bowel Disease and Infants Exposed in Utero

Emma Flanagan; Ralley Prentice; Emily K. Wright; Peter R. Gibson; Alyson L. Ross; Jakob Begun; Miles P. Sparrow; Rimma Goldberg; Ourania Rosella; Megan Burns; Katerina V. Kiburg; Sally J. Bell


Aliment Pharmacol Ther. 2022;55(6):700-704. 

In This Article

Abstract and Introduction


Background: Ustekinumab is increasingly used in pregnant women with inflammatory bowel disease (IBD). Existing safety data are reassuring, but the stability of ustekinumab levels in pregnancy, degree of transfer to the infant and time to infant clearance are unknown.

Methods: In this prospective observational study, ustekinumab-exposed women with IBD had trough levels measured in each trimester of pregnancy and at delivery. Infant ustekinumab levels were measured at delivery and ongoing until clearance was achieved. Trough ustekinumab level stability in individuals across pregnancy was compared by Skillings-Mack test. Spearman coefficients were used to correlate maternal and infant delivery levels, and median time to infant ustekinumab clearance was defined.

Results: 19 pregnant women receiving ustekinumab were included. There was no difference in ustekinumab levels across pregnancy in those with two or more representative trough levels (P = 0.83, n = 11). Infant delivery ustekinumab levels were higher than maternal levels, with a median infant:maternal ratio of 1.79 (IQR 1.26–3.1). There was a positive correlation between maternal and infant delivery ustekinumab levels (r = 0.75, P = 0.001) and an inverse correlation between the number of days from final antenatal dose and delivery infant ustekinumab level (r = −0.65, P = 0.006). Median time of infant ustekinumab clearance was 9 (range 6–19) weeks (n = 9).

Conclusion: Ustekinumab drug levels appear stable in pregnancy, with a delivery infant:maternal ratio similar to that of anti-TNFs. Infant ustekinumab clearance was complete by 20 weeks post-partum, however, infants exposed in utero should avoid live vaccination before 12 months of age until further clearance data are obtained.


Inflammatory bowel disease (IBD) commonly affects women of childbearing age, with the maintenance of disease remission prior to and during pregnancy important in order to optimise maternal and neonatal outcomes.[1] Ustekinumab, a human IgG1 kappa antibody against interleukin-12/23p40, is increasingly used in the management of IBD. IgG1 antibodies are actively transported across the placenta via interaction with placental Fc receptors from the second trimester, resulting in foetal exposure.[2] Existing safety data for the continuation of ustekinumab in pregnancy are reassuring.[1,3] Continuation of ustekinumab during conception and pregnancy is recommended for most women with IBD, although practice patterns of administering or withholding ustekinumab doses during the third trimester vary.[1,3]

Data regarding the stability of ustekinumab levels in pregnancy, its degree of transfer to exposed infants and the subsequent rate of infant clearance remain limited to case reports and small cohorts.[1,4,5] Observed physiologic changes in pregnancy, including increased plasma volume and decreased plasma albumin concentration, may theoretically alter the pharmacokinetics of biologic agents.[2] It is unclear whether ustekinumab levels remain stable throughout pregnancy, and if adjustment of the timing of the final antenatal ustekinumab dose to reduce infant exposure is necessary or effective. Infant ustekinumab clearance is important to inform when live vaccination is safe. Thus, the current study aimed to evaluate ustekinumab pharmacokinetics in women with IBD during pregnancy and in the exposed infant.