Infant Ustekinumab Clearance, Risk of Infection, and Development After Exposure During Pregnancy
Mette Julsgaard, Jantien W. Wieringa, Simon Mark Dahl Baunwall, Bo Martin Bibby, Gertjan J. Driessen, Linda Kievit, Jacob Broder Brodersen, Anja Poulsen, Jens Kjeldsen, Mette Mejlby Hansen, Hai Q. Tang, Christina L. Balmer, Henning Glerup, Jakob Benedict Seidelin, Kent V. Haderslev, Lise Svenningsen, Signe Wildt, Mie Agerbæk Juel, Anders Neumann, Jens Fuglsang, Tine Jess, Anne‐Mette Haase, Christian Lodberg Hvas, Jens Kelsen, C. Janneke van der Woude, Julie Korgaard, Thea Vestergaard, Uffe Lund Lystbæk, Anne T. Berg, Anette Tyrsted Mikkelsen, Anne Marie Holm, Annebirthe Bo Hansen, Ole Mathiesen, Jette Krüger Jensen, Lone Neumann, J. P. Boris, Marianne Lemming, M. Rahbek, Heidi Gram Søresen, Marie Højriis Storkholm, Jeanette Ziska, Else Marie Vestergaard, Sidsel Elisabeth Bøggild Ipsen, Jørgen Gram, Gunhild Brixen, Hanne Brix Westergaard, Lennart Friis‐Hansen, Bettina Friis Olsen, Heidi Fischer, Poul Jannik Bjerrum, Anne Haahr Ibsen, Vibeke Jaeger, Jesper Madsen, Lars Alling Møller, Karen Søeby, Jane Hansen Damm, Linda Hilsted, Lone Christiansen, Heidi Sharif, Britt Strøm Johansen, Karina Mattebjerg Dahl, Ebbe Langholz, Pia R. Kamstrup, Anja Jochumsen, Lene Drasbek Huusom, Lise Bathum, Charlotte Wilken‐Jensen
Abstract
BACKGROUND: Evidence on ustekinumab safety in pregnancy is gradually expanding, but its clearance in the postnatal period is unknown. The aim of this study was to investigate ustekinumab concentrations in umbilical cord blood and rates of clearance after birth, as well as how these correlate with maternal drug concentrations, risk of infection, and developmental milestones during the first year of life. METHODS: Pregnant women with inflammatory bowel disease were prospectively recruited from 19 hospitals in Denmark and the Netherlands between 2018 and 2022. Infant infections leading to hospitalization/antibiotics and developmental milestones were assessed. Serum ustekinumab concentrations were measured at delivery and specific time points. Nonlinear regression analysis was applied to estimate clearance. RESULTS: In 78 live-born infants from 76 pregnancies, we observed a low risk of adverse pregnancy outcomes and normal developmental milestones. At birth, the median infant-mother ustekinumab ratio was 2.18 (95% confidence interval, 1.69-2.81). Mean time to infant clearance was 6.7 months (95% confidence interval, 6.1-7.3 months). One in 4 infants at 6 months had an extremely low median concentration of 0.015 μg/mL (range 0.005-0.12 μg/mL). No variation in median ustekinumab concentration was noted between infants with (2.8 [range 0.4-6.9] μg/mL) and without (3.1 [range 0.7-11.0] μg/mL) infections during the first year of life (P = .41). CONCLUSIONS: No adverse signals after intrauterine exposure to ustekinumab were observed with respect to pregnancy outcome, infections, or developmental milestones during the first year of life. Infant ustekinumab concentration was not associated with risk of infections. With the ustekinumab clearance profile, live attenuated vaccination from 6 months of age seems of low risk.