Researchers Assess Placental Transfer of IBD Biologics

Different biological agents for inflammatory bowel disease (IBD) yield different placental pharmacokinetics, according to new research.

A team, led by Katarina Mitrova, Department of Paediatrics, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, assessed the placental transfer of ustekinumab and vedolizumab in pregnant patients with inflammatory bowel disease.

IBD is known to cause an increase in complications during pregnancy.

The Treatments

Vedolizumab is different for placental pharmacokinetics than other immunoglobulin G1 antibodies, which leads to lower drug levels in cord blood in contrast to maternal blood at the time of delivery.

In addition, the placental transfer of ustekinumab might have a similar pattern to anti-tumor necrosis factor agents.

However, must of the data regarding the 2 IBD treatments is limited for placental pharmacokinetics.

The Study

In the ongoing, prospective, multicenter, observation study, the investigators examined consecutive women who were exposed to either of the biologics within 2 months prior to conception or during pregnancy between March 2019 and December 2020. The study was conducted in 13 centers in the Czech Republic.

The team measured ustekinumab and vedolizumab levels in maternal and cord blood at the time of delivery.

Overall, there were 31 infant-mother pairs included in the study, 15 exposed to ustekinumab and 16 pairs exposed to vedolizumab. The investigators recorded data on the mother’s demographics and disease-related characteristics prior to conception, the smoking status, details on biologic treatment and concomitant medication at the time of conception and during pregnancy, disease activity at the time of conception and during pregnancy, the date and mode of delivery, pregnancy and IBD-related complications and the new-borns outcome.

The median maternal and newborn ustekinumab levels were 5.3 mg/l and 10.3 mg/l, respectively and the median infant-to-maternal ratio was 1.7.The median maternal and cord vedolizumab levels were 7.3 mg/l and 4.5 mg/l and the median infant-to-maternal ratio was 0.66.

Results

The investigators found the ustekinumab levels in cord blood positively correlated with the maternal levels at delivery (P = 0.751; P = 0.001).

On the other hand, there was no correlation with the timing of the last drug administration.

For vedolizumab, the levels in cord blood demonstrated significant positive correlation with the maternal levels (P = 0.831; P <0.001), as well as the gestational week of the last infusion (P = 0.736; P = 0.001).

The safety profile of ustekinumab does not indicate any negative safety signals and limited evidence on vedolizumab during pregnancy also did not raise any safety concerns for either the mothers or the newborns.

“Vedolizumab demonstrated different placental pharmacokinetics, leading to lower drug levels in cord blood compared to maternal blood at delivery; in contrast, the placental transfer of ustekinumab seems to have a pattern similar to anti-tumor necrosis factor (TNF) agents,” the authors wrote.

The study, “Differences in the placental pharmacokinetics of vedolizumab and ustekinumab during pregnancy in women with inflammatory bowel disease: a prospective multicenter study,” was published online in Therapeutic Advances in Gastroenterology.