Fetal Safety of TNF Inhibitors in Humans

Review Article


Nada Djokanovic and Gideon Koren

Affiliation: The Motherisk Program, Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, University of Toronto, Toronto, Canada


ABSTRACT

Tumor necrosis factor (TNF)‐α inhibitors (infliximab, etanercept, and adalimumab) are marked as pregnancy category B by the US Food and Drug Administration (FDA), indicating that animal studies have not demonstrated fetal risk. Previously published limited human experience has been reassuring, showing no increased risk of congenital malformations in children born to women taking TNF inhibitors. However, recently, some concerns have been raised regarding their safety in pregnancy. This review provides the most current information on the safety of anti‐TNF therapy in pregnancy. A growing body of evidence suggests that infliximab and adalimumab are low risk in pregnancy. Regarding etanercept, the data available today do not suggest that etanercept is a major human teratogen, and it is quite possible that its teratogenic risk does not exceed the baseline rate of congenital malformations in general population.

Keywords: tumor necrosis factor (TNF) inhibitors, infliximab, etanercept, adalimumab, pregnancy, women, fetal risk
Correspondence: Gideon Koren, The Motherisk Program, Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada M5G 1X8. e‐mail: gkoren@sickkids.ca