Placental transfer of anti-tumor necrosis factor agents in pregnant patients with inflammatory bowel disease

Clin Gastroenterol Hepatol. 2013 Mar;11(3):286-92; quiz e24. doi: 10.1016/j.cgh.2012.11.011. Epub 2012 Nov 28.

Abstract

Background & aims: Some women with inflammatory bowel disease require therapy with tumor necrosis factor (TNF) antagonists during pregnancy. It is not clear whether these drugs are transferred to the fetus via the placenta and then cleared, or whether structurally different TNF antagonists have different rates of transfer.

Methods: We studied 31 pregnant women with inflammatory bowel disease receiving infliximab (IFX, n = 11), adalimumab (ADA, n = 10), or certolizumab (CZP, n = 10). Serum concentrations of the drugs were measured at birth in the mother, infant, and in cord blood, and then monthly in the infant until the drugs were undetectable. Drug concentrations in the cord and the infant at birth were compared with those of the mother.

Results: Concentrations of IFX and ADA, but not CZP, were higher in infants at birth and their cords than in their mothers. The levels of CZP in infants and their cords were less than 2 μg/mL. The median level of IFX in the cord was 160% that of the mother, the median level of ADA in the cord was 153% that of the mother, and the median level of CZP in the cord was 3.9% that of the mother. IFX and ADA could be detected in the infants for as long as 6 months. No congenital anomalies or serious complications were reported.

Conclusions: The TNF antagonists IFX and ADA are transferred across the placenta and can be detected in infants at birth; the drugs were detected in infants up to 6 months after birth. CZP has the lowest level of placental transfer, based on levels measured in cords and infants at birth, of the drugs tested.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab
  • Adult
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / pharmacokinetics*
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / pharmacokinetics*
  • Certolizumab Pegol
  • Female
  • Fetal Blood / chemistry
  • Follow-Up Studies
  • Humans
  • Immunoglobulin Fab Fragments / administration & dosage
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / pharmacokinetics*
  • Infant
  • Infant, Newborn
  • Inflammatory Bowel Diseases / drug therapy*
  • Infliximab
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / pharmacokinetics*
  • Pregnancy
  • Pregnancy Complications / drug therapy*
  • Serum / chemistry*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Immunoglobulin Fab Fragments
  • Immunologic Factors
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Polyethylene Glycols
  • Infliximab
  • Adalimumab
  • Certolizumab Pegol