Differences in the placental disposition of TNF inhibitors uncovered

19 March 2020

Tumor necrosis factor (TNF) inhibitors are increasingly applied during pregnancy without clear knowledge of the impact on placenta and fetus. In a recent paper published in Clinical Pharmacology and Therapeutics, researchers from the Departments of Pharmacology and Toxicology, Obstetrics and Gynecology, and Health Evidence, in collaboration with Sanquin Diagnostic Services, investigated the placental handling of the TNF inhibitors infliximab and etanercept.
 
In their study, Gaby Eliesen and colleagues combined clinical observations with preclinical studies. In clinical work, the placental drug disposition was studied in women with autoimmune diseases who were treated with TNF inhibitors throughout pregnancy. In the preclinical studies, fetal and maternal circulations of term human, TNF-inhibitor-naïve, placentas were re-established immediately after birth. In a controlled laboratory setting, it was then studied how the placenta handled the drugs in the initial six hours after first exposure ex vivo.
 
A main finding of the study was that infliximab concentrations in placenta tissue reached markedly higher levels than etanercept. This was observed both in the clinical cases as well as in the ex vivo perfused placentas. The authors indicate that the difference in placental tissue exposure may be of clinical relevance and warrants further investigation. More specifically, future studies should look into the occurrence of placental TNF inhibition and possible consequences thereof.