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; Linda Maria Hilsted; Lone Christiansen; Heidi Sharif; Ebbe Langholz; Pia Rørbæk Kamstrup; Lene Drasbek Huusom; Lise  Bathum; Charlotte Wilken-Jensen; Hanne Brix Westergaard; Lennart Jan Friis-Hansen

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, Linda Maria Hilsted (Member of study group), Lone Christiansen (Member of study group), Heidi Sharif (Member of study group), Ebbe Langholz (Member of study group), Pia Rørbæk Kamstrup (Member of study group), Lene Drasbek Huusom (Member of study group), Lise Bathum (Member of study group), Charlotte Wilken-Jensen (Member of study group), Hanne Brix Westergaard (Member of study group), Lennart Jan Friis-Hansen (Member of study group)

^*Corresponding author for this work

5 Citations (Scopus)

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.

Original language	English
Journal	Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
Volume	23
Issue number	1
Pages (from-to)	134-143
Number of pages	10
ISSN	1542-3565
DOIs	https://doi.org/10.1016/j.cgh.2024.01.008
Publication status	Published - Jan 2025

Keywords

Adult
Denmark/epidemiology
Female
Fetal Blood/chemistry
Humans
Infant
Infant, Newborn
Inflammatory Bowel Diseases/drug therapy
Male
Netherlands
Pregnancy
Pregnancy Complications/drug therapy
Pregnancy Outcome
Prospective Studies
Ustekinumab/pharmacokinetics
Young Adult

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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., ... Friis-Hansen, L. J. (2025). Infant ustekinumab Clearance, Risk of Infection, and Development after exposure during pregnancy. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 23(1), 134-143. https://doi.org/10.1016/j.cgh.2024.01.008

Infant ustekinumab Clearance, Risk of Infection, and Development after exposure during pregnancy. / Julsgaard, Mette; Wieringa, Jantien W; Baunwall, Simon M D et al.
In: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, Vol. 23, No. 1, 01.2025, p. 134-143.

Research output: Contribution to journal › Journal article › Research › peer-review

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, Hilsted, LM, Christiansen, L, Sharif, H, Langholz, E , Kamstrup, PR, Huusom, LD, Bathum, L , Wilken-Jensen, C , Westergaard, HB & Friis-Hansen, LJ 2025, 'Infant ustekinumab Clearance, Risk of Infection, and Development after exposure during pregnancy', Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, vol. 23, no. 1, pp. 134-143. https://doi.org/10.1016/j.cgh.2024.01.008

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

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.",

keywords = "Adult, Denmark/epidemiology, Female, Fetal Blood/chemistry, Humans, Infant, Infant, Newborn, Inflammatory Bowel Diseases/drug therapy, Male, Netherlands, Pregnancy, Pregnancy Complications/drug therapy, Pregnancy Outcome, Prospective Studies, Ustekinumab/pharmacokinetics, Young Adult",

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} and Hilsted, {Linda Maria} and Lone Christiansen and Heidi Sharif and Ebbe Langholz and Kamstrup, {Pia R{\o}rb{\ae}k} and Huusom, {Lene Drasbek} and Lise Bathum and Charlotte Wilken-Jensen and Westergaard, {Hanne Brix} and Friis-Hansen, {Lennart Jan}",

note = "Copyright {\textcopyright} 2024. Published by Elsevier Inc.",

year = "2025",

month = jan,

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

language = "English",

volume = "23",

pages = "134--143",

journal = "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association",

issn = "1542-3565",

publisher = "W.B./Saunders Co",

number = "1",

}

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

A2 - Hilsted, Linda Maria

A2 - Christiansen, Lone

A2 - Sharif, Heidi

A2 - Langholz, Ebbe

A2 - Kamstrup, Pia Rørbæk

A2 - Huusom, Lene Drasbek

A2 - Bathum, Lise

A2 - Wilken-Jensen, Charlotte

A2 - Westergaard, Hanne Brix

A2 - Friis-Hansen, Lennart Jan

PY - 2025/1

Y1 - 2025/1

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 - Adult

KW - Denmark/epidemiology

KW - Female

KW - Fetal Blood/chemistry

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Inflammatory Bowel Diseases/drug therapy

KW - Male

KW - Netherlands

KW - Pregnancy

KW - Pregnancy Complications/drug therapy

KW - Pregnancy Outcome

KW - Prospective Studies

KW - Ustekinumab/pharmacokinetics

KW - Young Adult

UR - http://www.scopus.com/inward/record.url?scp=85186093313&partnerID=8YFLogxK

U2 - 10.1016/j.cgh.2024.01.008

DO - 10.1016/j.cgh.2024.01.008

M3 - Journal article

C2 - 38278191

SN - 1542-3565

VL - 23

SP - 134

EP - 143

JO - Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association

JF - Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association

IS - 1

ER -

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

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