Differences in the placental pharmacokinetics of vedolizumab and ustekinumab during pregnancy in women with inflammatory bowel disease: a prospective multicentre study

• Published in: Therapeutic advances in gastroenterology Vol. 14; p. 17562848211032790
• Main Authors: Mitrova, Katarina, Pipek, Barbora, Bortlik, Martin, Bouchner, Ludek, Brezina, Jan, Douda, Tomas, Drasar, Tomas, Drastich, Pavel, Falt, Premysl, Klvana, Pavel, Leksa, Vaclav, Novotny, Ales, Svoboda, Pavel, Skorpik, Jan, Ulbrych, Jan, Veinfurt, Marek, Zborilova, Blanka, Lukas, Milan, Duricova, Dana
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 2021; Sage Publications Ltd; SAGE Publishing
• Subjects: Gastroenterology; Inflammatory bowel disease; Monoclonal antibodies; Original Research; Pharmacokinetics; Tumor necrosis factor-TNF; vedolizumab; ustekinumab; pregnancy
• ISSN: 1756-2848; 1756-283X; 1756-2848
• DOI: 10.1177/17562848211032790

Background:
Vedolizumab demonstrated different placental pharmacokinetics than other immunoglobulin G1 antibodies, leading to lower drug levels in cord blood in contrast to maternal blood at the time of delivery. The placental transfer of ustekinumab seems to have a pattern similar to anti-tumour necrosis factor agents. Current evidence on the placental pharmacokinetics of vedolizumab and ustekinumab is limited. We aimed to assess the placental transfer of ustekinumab and vedolizumab in pregnant patients with inflammatory bowel disease.
Methods:
Consecutive women from a prospective observational study who were exposed to ustekinumab or vedolizumab within 2 months prior to conception or during pregnancy were included. Ustekinumab and vedolizumab levels were measured in maternal and cord blood at the time of delivery.
Results:
Drug levels were available in 31 infant-mother pairs (15 exposed to ustekinumab and 16 to vedolizumab). The median maternal and newborn ustekinumab levels were 5.3 mg/l and 10.3 mg/l, respectively (the median infant-to-maternal ratio was 1.7), while the median maternal and cord vedolizumab levels were 7.3 mg/l and 4.5 mg/l (the median infant-to-maternal ratio was 0.66). The ustekinumab levels in cord blood positively correlated with the maternal levels at delivery (ρ = 0.751, p = 0.001). However, no correlation with the timing of the last drug administration was found. In contrast, the vedolizumab levels in cord blood demonstrated significant positive correlation with the maternal levels (ρ = 0.831, p < 0.001) along with the gestational week of the last infusion (ρ = 0.736, p = 0.001).
Conclusion:
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-tumour necrosis factor (TNF) agents.