Is Enbrel (etanercept) safe to use during pregnancy?

Etanercept (Enbrel) Use During Pregnancy

Etanercept can be safely continued during pregnancy, particularly in the first and second trimesters, with consideration for discontinuation in the third trimester if disease is well controlled. 1, 2

Safety Profile of Etanercept in Pregnancy

• Etanercept is conditionally recommended for use prior to and during pregnancy by the 2020 American College of Rheumatology guidelines for management of reproductive health in rheumatic diseases 1
• The FDA drug label notes that while there is a higher proportion of birth defects in etanercept-exposed pregnancies compared to unexposed patients with chronic inflammatory diseases, there is no consistent pattern of birth defects, suggesting disease severity may impact outcomes rather than the medication itself 2
• Etanercept contains an Fc IgG1 construct that does not cross the placenta in significant concentrations until the second trimester 1

Recommendations by Trimester

First and Second Trimesters

• Continuing etanercept is conditionally recommended during the first and second trimesters of pregnancy 1
• Studies show minimal placental transfer during early pregnancy, making it relatively safe during this period 1
• Maintaining disease control during pregnancy is important as active disease increases risk of adverse pregnancy outcomes 2

Third Trimester

• If disease is well-controlled, consider discontinuing etanercept in the third trimester 1
• If active disease persists, continuing etanercept through delivery can be considered, with the understanding that the neonate will have significant serum levels of the drug 1
• Cord blood levels at delivery have been reported to range from undetectable to 32% of maternal serum levels 2

Monitoring and Special Considerations

• Live or live-attenuated vaccines should be avoided in infants exposed to etanercept in utero 2
• Among TNF inhibitors, certolizumab pegol may be preferable for pregnant patients due to its minimal placental transfer (lacks an Fc chain), though etanercept remains a reasonable option 1, 3
• Case reports have documented successful pregnancies with etanercept use throughout gestation 4, 5

Breastfeeding Considerations

• Etanercept is present in low levels in human milk but is not detected in the plasma of breastfed infants 2
• There have been no consistent reports of adverse events in breastfed infants over decades of use 2
• The benefits of breastfeeding should be considered along with the mother's clinical need for disease control 2

Risk-Benefit Assessment

• The risk of untreated or poorly controlled rheumatic disease during pregnancy may outweigh potential risks of etanercept exposure 1, 2
• Disease activity is correlated with adverse pregnancy outcomes including fetal loss, preterm delivery, low birth weight, and small for gestational age births 2
• If disease cannot be controlled with medications considered compatible with pregnancy, physicians and patients should discuss and weigh possible risks from medications versus risks of uncontrolled disease 1