Vedolizumab and ustekinumab levels in pregnant women with inflammatory bowel disease and infants exposed in-utero

Background and aims Vedolizumab and ustekinumab pharmacokinetics in pregnancy and the infant following 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 multicentre prospective observational cohort study recruited pregnant or preconception women with Inflammatory Bowel Disease receiving vedolizumab or ustekinumab. Trough drug levels, clinical and biochemical data were documented pre-conception, 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 to two years of age. Results 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 weeks, range 5-19, n=32) than ustekinumab (14 weeks, range 9-36, n=17) and correlated positively with infant delivery level. 32/41 (88%) and 17/30 (67%) of 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. Conclusion Maternal vedolizumab levels decrease, while ustekinumab levels remain 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.