Infant ustekinumab Clearance, Risk of Infection, and Development after exposure during pregnancy

Mette Julsgaard; Jantien W Wieringa; Simon M D Baunwall; Bo M Bibby; Gertjan J A Driessen; Linda Kievit; Jacob B Brodersen; Anja Poulsen; Jens Kjeldsen; Mette M Hansen; Hai Q Tang; Christina L Balmer; Henning Glerup; Jakob B Seidelin; Kent V Haderslev; Lise Svenningsen; Signe Wildt; Mie A Juel; Anders Neumann; Jens Fuglsang; Tine Jess; Anne-Mette Hasse; Christian L Hvas; Jens Kelsen; C Janneke van der Woude; NEXUS Collaborator Group

doi:10.1016/j.cgh.2024.01.008

Infant ustekinumab Clearance, Risk of Infection, and Development after exposure during pregnancy

Mette Julsgaard^*, Jantien W Wieringa, Simon M D Baunwall, Bo M Bibby, Gertjan J A Driessen, Linda Kievit, Jacob B Brodersen, Anja Poulsen, Jens Kjeldsen, Mette M Hansen, Hai Q Tang, Christina L Balmer, Henning Glerup, Jakob B Seidelin, Kent V Haderslev, Lise Svenningsen, Signe Wildt, Mie A Juel, Anders Neumann, Jens FuglsangTine Jess, Anne-Mette Hasse, Christian L Hvas, Jens Kelsen, C Janneke van der Woude, NEXUS Collaborator Group

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND AND AIM: 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. Non-linear 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%CI,1.69-2.81). Mean time to infant clearance was 6.7 (95%CI,6.1-7.3) months. One-in-four infants at 6 months had an extremely low median concentration of 0.015 µg/ml (range:0.005-0.12) . No variation in median ustekinumab concentration was noted between infants with (2.8µg/ml; range,0.4-6.9) and without (3.1µg/ml; range,0.7-11.0) infections during the first year of life (p=0.41). 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.

Original language	English
Journal	Clinical gastroenterology and hepatology
DOIs	https://doi.org/10.1016/j.cgh.2024.01.008
Publication status	E-pub ahead of print - 24 Jan 2024

Keywords

Pregnancy
infant infections
inflammatory bowel disease
ustekinumab

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Julsgaard, M., Wieringa, J. W., Baunwall, S. M. D., Bibby, B. M., Driessen, G. J. A., Kievit, L., Brodersen, J. B., Poulsen, A., Kjeldsen, J., Hansen, M. M., Tang, H. Q., Balmer, C. L., Glerup, H., Seidelin, J. B., Haderslev, K. V., Svenningsen, L., Wildt, S., Juel, M. A., Neumann, A., ... NEXUS Collaborator Group (2024). Infant ustekinumab Clearance, Risk of Infection, and Development after exposure during pregnancy. Clinical gastroenterology and hepatology. Advance online publication. https://doi.org/10.1016/j.cgh.2024.01.008

@article{ae947040bd55477d80ab1f9796dbcdce,

title = "Infant ustekinumab Clearance, Risk of Infection, and Development after exposure during pregnancy",

abstract = "BACKGROUND AND AIM: 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. Non-linear 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%CI,1.69-2.81). Mean time to infant clearance was 6.7 (95%CI,6.1-7.3) months. One-in-four infants at 6 months had an extremely low median concentration of 0.015 µg/ml (range:0.005-0.12) . No variation in median ustekinumab concentration was noted between infants with (2.8µg/ml; range,0.4-6.9) and without (3.1µg/ml; range,0.7-11.0) infections during the first year of life (p=0.41). 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.",

keywords = "Pregnancy, infant infections, inflammatory bowel disease, ustekinumab",

author = "Mette Julsgaard and Wieringa, {Jantien W} and Baunwall, {Simon M D} and Bibby, {Bo M} and Driessen, {Gertjan J A} and Linda Kievit and Brodersen, {Jacob B} and Anja Poulsen and Jens Kjeldsen and Hansen, {Mette M} and Tang, {Hai Q} and Balmer, {Christina L} and Henning Glerup and Seidelin, {Jakob B} and Haderslev, {Kent V} and Lise Svenningsen and Signe Wildt and Juel, {Mie A} and Anders Neumann and Jens Fuglsang and Tine Jess and Anne-Mette Hasse and Hvas, {Christian L} and Jens Kelsen and {Janneke van der Woude}, C and {NEXUS Collaborator Group}",

year = "2024",

month = jan,

day = "24",

doi = "10.1016/j.cgh.2024.01.008",

language = "English",

journal = "Clinical gastroenterology and hepatology",

issn = "1542-3565",

publisher = "Elsevier Science",

}

Julsgaard, M, Wieringa, JW, Baunwall, SMD, Bibby, BM, Driessen, GJA, Kievit, L, Brodersen, JB, Poulsen, A, Kjeldsen, J, Hansen, MM, Tang, HQ, Balmer, CL, Glerup, H, Seidelin, JB, Haderslev, KV, Svenningsen, L, Wildt, S, Juel, MA, Neumann, A, Fuglsang, J, Jess, T, Hasse, A-M, Hvas, CL, Kelsen, J, Janneke van der Woude, C & NEXUS Collaborator Group 2024, 'Infant ustekinumab Clearance, Risk of Infection, and Development after exposure during pregnancy', Clinical gastroenterology and hepatology. https://doi.org/10.1016/j.cgh.2024.01.008

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 - Hasse, Anne-Mette

AU - Hvas, Christian L

AU - Kelsen, Jens

AU - Janneke van der Woude, C

AU - NEXUS Collaborator Group

PY - 2024/1/24

Y1 - 2024/1/24

N2 - BACKGROUND AND AIM: 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. Non-linear 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%CI,1.69-2.81). Mean time to infant clearance was 6.7 (95%CI,6.1-7.3) months. One-in-four infants at 6 months had an extremely low median concentration of 0.015 µg/ml (range:0.005-0.12) . No variation in median ustekinumab concentration was noted between infants with (2.8µg/ml; range,0.4-6.9) and without (3.1µg/ml; range,0.7-11.0) infections during the first year of life (p=0.41). 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 AND AIM: 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. Non-linear 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%CI,1.69-2.81). Mean time to infant clearance was 6.7 (95%CI,6.1-7.3) months. One-in-four infants at 6 months had an extremely low median concentration of 0.015 µg/ml (range:0.005-0.12) . No variation in median ustekinumab concentration was noted between infants with (2.8µg/ml; range,0.4-6.9) and without (3.1µg/ml; range,0.7-11.0) infections during the first year of life (p=0.41). 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 - Pregnancy

KW - infant infections

KW - inflammatory bowel disease

KW - ustekinumab

U2 - 10.1016/j.cgh.2024.01.008

DO - 10.1016/j.cgh.2024.01.008

M3 - Article

SN - 1542-3565

JO - Clinical gastroenterology and hepatology

JF - Clinical gastroenterology and hepatology

ER -