Is Enbrel (Etanercept) Safe During Pregnancy?

What does the evidence say about enbrel during pregnancy?

1. MotherToBaby reports that most etanercept studies have not found a higher rate of birth differences; studies reporting increases found no consistent pattern and could not fully separate medicine effects from the underlying condition. 1
2. A prospective cohort of 495 first-trimester TNF-inhibitor exposures, including 140 etanercept exposures, found higher combined-class major-malformation and preterm-birth rates than 1,532 general-population controls, but had no disease-matched comparison group. 2
3. A separate retrospective study with inflammatory-disease comparison groups found no significant etanercept-associated major-malformation increase in chronic inflammatory arthritis or psoriasis, but confidence intervals were wide and residual confounding remained possible. 3
4. The 2024 EULAR update states that all TNF inhibitors may be used throughout pregnancy after individualized benefit-risk assessment and regards all biologic disease-modifying antirheumatic drugs as compatible with breastfeeding. 4
5. LactMed reports low etanercept concentrations in milk and poor expected infant absorption, but notes that long-term breastfeeding outcome data remain limited and available infant series are small. 5

Is enbrel safe in each trimester?

• First trimester. First-trimester studies are observational. One prospective TNF-inhibitor cohort used a general-population comparison rather than a disease-matched group, so its higher combined-class malformation rate cannot isolate etanercept from disease activity or other medicines.
• Second trimester. Disease control, prior response, infection history, and other immune-modifying medicines should guide continuation. Current EULAR recommendations permit TNF inhibitors throughout pregnancy after individualized risk-benefit assessment rather than requiring a fixed pause week.
• Third trimester. Placental transfer and newborn planning become more relevant later in pregnancy, but cord-blood findings do not prove birth-outcome safety. Record the last dose and ensure the prenatal and pediatric teams know about exposure.