Can tumor necrosis factor inhibitors be safely used in pregnancy?
OBJECTIVE
We review available safety data for use of currently approved tumor necrosis factor (TNF) inhibitors during pregnancy and lactation and suggest guidelines for use of these agents among women of reproductive age. Method. Although regulatory agencies encourage the inclusion of pregnant women and those of child-bearing age in randomized controlled trials, pregnant and lactating women have universally been excluded from studies because of unknown or potential risks to the fetus. Thus, strong evidence-based treatment recommendations during pregnancy are usually lacking and safety information is derived from voluntary reports of adverse events during postmarketing surveillance or via uncontrolled, observational studies, reviewed here.


RESULTS
Uncommon adverse pregnancy outcomes observed with TNF inhibitor therapy appear to approximate those seen in women not receiving such therapy and may include premature birth, miscarriage, low birthweight, hypertension, and preeclampsia. There are rare reports of fetal malformations or congenital anomalies in patients exposed to TNF inhibitors during conception or pregnancy. However, the incidence of these events appears to be far below the 3% rate of congenital anomalies in the general population.


CONCLUSIONS
If the activity or disease severity precludes the cessation of a TNF inhibitor and/or DMARD, uncontrolled observations suggest that conception and early pregnancy are not adversely affected by use of TNF inhibitors. Nearly 70% of pregnant patients can discontinue their TNF inhibitor early in the pregnancy (or with determination of pregnancy) without augmenting maternal or fetal risks.
Ali
Yaser M
YM
Department of Clinical Immunology and Allergy, University of Toronto, Toronto, Ontario, Canada. yaser.ali@utoronto.ca
Kuriya
Bindee
B
Orozco
Catalina
C
Cush
John J
JJ
Keystone
Edward C
EC
D000014:Abnormalities, Drug-Induced; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D005260:Female; D005333:Fetus / Q000187:drug effects; D017408:Guidelines as Topic; D006801:Humans; D007774:Lactation / Q000187:drug effects*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced; D011256:Pregnancy Outcome; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced; D016032:Randomized Controlled Trials as Topic; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha