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Clin Pharmacol Ther. 2020 Mar 10. doi: 10.1002/cpt.1827. [Epub ahead of print]

Assessment of placental disposition of infliximab and etanercept in women with autoimmune disease and in the ex vivo perfused placenta.

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Department of Pharmacology & Toxicology, Radboud university medical center, Nijmegen, The Netherlands.
Department of Obstetrics and Gynecology, Radboud university medical center, Nijmegen, The Netherlands.
Sanquin Diagnostic Services, Amsterdam, The Netherlands.
Department for Health Evidence, Radboud university medical center, Nijmegen, The Netherlands.


Tumor necrosis factor (TNF) inhibitors are increasingly applied during pregnancy without clear knowledge of the impact on placenta and fetus. We assessed placental transfer and exposure to infliximab (n=3) and etanercept (n=3) in women with autoimmune diseases. Furthermore, we perfused healthy term placentas for 6h with 100 µg/mL infliximab (n=4) or etanercept (n=5). In pregnant women, infliximab transferred into cord blood but also entered the placenta (cord-to-maternal ratio of 1.6±0.4, placenta-to-maternal ratio of 0.3±0.1, n=3). For etanercept, a cord-to-maternal ratio of 0.04 and placenta-to-maternal ratio of 0.03 was observed in one patient only. In ex vivo placenta perfusions, the extent of placental transfer did not differ between the drugs. Final concentrations in the fetal compartment for infliximab and etanercept were 0.3±0.3 µg/mL and 0.2±0.2 µg/mL, respectively. However, in placental tissue, infliximab levels exceeded those of etanercept (19±6 µg/g versus 1±3 µg/g, p<0.001). In conclusion, tissue exposure to infliximab is higher than that of etanercept both in vivo as well as in ex vivo perfused placentas. However, initial placental transfer, as observed ex vivo, does not differ between infliximab and etanercept when administered in equal amounts. The difference in placental tissue exposure to infliximab and etanercept may be of clinical relevance and warrants further investigation. More specifically, we suggest that future studies should look into the occurrence of placental TNF inhibition and possible consequences thereof.


TNF inhibitors; autoimmune diseases; placental exposure; placental transfer; pregnancy


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