Clin Gastroenterol Hepatol. 2025 Jan;23(1):124-133.e7.doi: 10.1016/j.cgh.2024.02.025. Epub 2024 Mar 15.

Ralley Prentice ¹, Emma Flanagan ², Emily K Wright ², Peter R Gibson ³, Sam Rosella ³, Ourania Rosella ³, Jakob Begun ⁴, Yoon-Kyo An ⁴, Ian C Lawrance ⁵, Michael A Kamm ², Miles Sparrow ³, Rimma Goldberg ⁶, Lani Prideaux ⁷, Sara Vogrin ⁸, Katerina V Kiburg ⁸, Alyson L Ross ⁹, Megan Burns ⁷, Sally J Bell ¹⁰

Author information

¹Department of Gastroenterology, Monash Health, Clayton, Victoria, Australia; Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia; Centre of Inflammatory Disease, Department of Medicine, Monash University, Clayton, Victoria, Australia. Electronic address: ralley.prentice@monash.edu.

²Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia; University of Melbourne, Parkville, Victoria, Australia.

³Department of Gastroenterology, Central Clinical School, Monash University and Alfred Health, Melbourne, Victoria, Australia.

⁴Department of Gastroenterology, Mater Hospital, Brisbane, Queensland, Australia.

⁵School of Medicine and Pharmacology, Faculty of Medicine and Dentistry at the University of Western Australia, Perth, Western Australia, Australia; St John of God Subiaco Hospital, Perth, Western Australia, Australia.

⁶Department of Gastroenterology, Monash Health, Clayton, Victoria, Australia; Centre of Inflammatory Disease, Department of Medicine, Monash University, Clayton, Victoria, Australia.

⁷Department of Gastroenterology, Monash Health, Clayton, Victoria, Australia.

⁸University of Melbourne, Parkville, Victoria, Australia.

⁹Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia.

¹⁰Department of Gastroenterology, Monash Health, Clayton, Victoria, Australia; Centre of Inflammatory Disease, Department of Medicine, Monash University, Clayton, Victoria, Australia; University of Melbourne, Parkville, Victoria, Australia.

Abstract

Background & aims: Vedolizumab and ustekinumab pharmacokinetics in pregnancy and the infant after in utero exposure remain incompletely defined. We aim to define the antenatal stability of ustekinumab and vedolizumab levels and the time at which infant drug levels become undetectable.

Methods: This multicenter prospective observational cohort study recruited pregnant or preconception women with inflammatory bowel disease receiving vedolizumab or ustekinumab. Trough drug levels, clinical data, and biochemical data were documented preconception, during each trimester of pregnancy, and postpartum. Maternal and cord blood drug levels were measured at delivery and in infants until undetectable. Infant outcomes were assessed until 2 years of age.

Results: A total of 102 participants (vedolizumab, n = 58) were included. The majority of mothers were, and remained, in clinical and biochemical remission. Maternal vedolizumab levels decreased over the course of pregnancy in association with increasing weight, rather than increasing gestation. Maternal ustekinumab levels remained stable. The median time to drug becoming undetectable in the infant was shorter for vedolizumab (11 wk; range, 5-19 wk; n = 32) than ustekinumab (14 wk; range, 9-36 wk; n = 17) and correlated positively with infant delivery level. Thirty-two of 41 (88%) and 17 of 30 (67%) vedolizumab- and ustekinumab-exposed infants had undetectable drug levels by 15 weeks of age, respectively. Pregnancy and infant outcomes were favorable. Twenty infants with undetectable drug levels received the rotavirus vaccine, with no adverse reactions reported.

Conclusions: Maternal vedolizumab levels decreased, whereas ustekinumab levels remained stable over the course of pregnancy. Most vedolizumab- and approximately half of ustekinumab-exposed infants had undetectable drug levels by 15 weeks of age. No concerning maternal or infant safety signals were identified.