TY - JOUR

T1 - Infant Ustekinumab Clearance, Risk of Infection, and Development After Exposure During Pregnancy

AU - Julsgaard, Mette

AU - Wieringa, Jantien W.

AU - Baunwall, Simon M.D.

AU - Bibby, Bo M.

AU - Driessen, Gertjan J.A.

AU - Kievit, Linda

AU - Brodersen, Jacob B.

AU - Poulsen, Anja

AU - Kjeldsen, Jens

AU - Hansen, Mette M.

AU - Tang, Hai Q.

AU - Balmer, Christina L.

AU - Glerup, Henning

AU - Seidelin, Jakob B.

AU - Haderslev, Kent V.

AU - Svenningsen, Lise

AU - Wildt, Signe

AU - Juel, Mie A.

AU - Neumann, Anders

AU - Fuglsang, Jens

AU - Jess, Tine

AU - Haase, Anne Mette

AU - Hvas, Christian L.

AU - Kelsen, Jens

AU - Janneke van der Woude, C.

AU - Korgaard, Julie

AU - Vestergaard, Thea

AU - Lystbæk, Uffe Lund

AU - Berg, Anne

AU - Mikkelsen, Anette Tyrsted

AU - Holm, Anne Marie

AU - Hansen, Annebirthe Bo

AU - Mathiesen, Ole

AU - Jensen, Jette Krüger

AU - Neumann, Lone

AU - Boris, Jane

AU - Lemming, Marianne

AU - Rahbek, Marianne

AU - Westergaard, Hanne Brix

AU - Friis-Hansen, Lennart Jan

AU - Møller, Lars Alling

AU - Søeby, Karen

AU - Hilsted, Linda

AU - Christiansen, Lone

AU - Sharif, Heidi

AU - Langholz, Ebbe

AU - Kamstrup, Pia R.

AU - Jochumsen, Anja

AU - Huusom, Lene Drasbek

AU - Wilken-Jensen, Charlotte

AU - NEXUS Collaborator Group

N1 - Publisher Copyright: © 2024 AGA Institute

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - Infant Infections

KW - Inflammatory Bowel Disease

KW - Pregnancy

KW - Ustekinumab

U2 - 10.1016/j.cgh.2024.01.008

DO - 10.1016/j.cgh.2024.01.008

M3 - Journal article

C2 - 38278191

AN - SCOPUS:85186093313

JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

SN - 1542-3565

ER -