n exposure groups (eg. disease severity) may have impacted the occurrence of birth defects (seeData). In animal reproduction studies with pregnant rats and rabbits, no fetal harm or malformations were observedwith subcutaneous administration of etanercept during the period of organogenesis at doses that achieved systemic
exposures 48 to 58 times the exposure in patients treated with 50 mg etanercept once weekly (see Data).
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated backgroundrisk of major birth defects and miscarriage for the indicated populations is unknown. In the United States, about2-4% of liveborn babies have a major birth defect and about 15-20% of pregnancies end in miscarriage, regardless of
drug exposure.
Clinical Considerations
Fetal/Neonatal adverse reactions
The risk of fetal/neonatal adverse reactions with in utero exposure to etanercept is unknown. Risks and benefitsshould be considered prior to administering live or live-attenuated vaccines to infants exposed to Eticovo in utero [seeUse in Specific Populations (8.4)].
Data
Human Data
A prospective cohort pregnancy registry conducted by OTIS in the US and Canada between 2000 and 2012 comparedthe risk of major birth defects in liveborn infants of women with rheumatic diseases or psoriasis exposed to etanerceptin the first trimester. The proportion of major birth defects among liveborn infants in the
etanercept-exposed (N = 319) and diseased etanercept unexposed cohorts (N = 144) was 9.4% and 3.5%, respectively.
The findings showed no statistically significant increased risk of minor birth defects and no pattern of major or minorbirth defects.
A Scandinavian study compared the risk of major birth defects in liveborn infants of women with chronic
inflammatory disease (CID) exposed to TNF-inhibitors during early pregnancy. Women were identified from theDanish (2004-2012) and Swedish (2006-2012) population basedhealth registers. The proportion of major birth defects
among liveborn infants in the etanercept-exposed (N=344) and CID etanercept unexposed cohorts(N = 21,549) was 7.0% and 4.7%, respectively.
Overall, while both the OTIS Registry and Scandinavian study show a higher proportion of major birth defects inetanercept-exposed patients compared to diseased etanercept unexposed patients, the lack of pattern of birth defectsis reassuring and differences between exposure groups (e.g. disease severity) may have impacted the occurrence ofbirth defects.
Three case reports from the literature showed that cord blood levels of etanercept at delivery, in infants born towomen administered etanercept during pregnancy, were between 3% and 32% of the maternal serum level.
Animal Data
In embryofetal development studies with etanercept administered during the period of organogenesis to pregnant ratsfrom gestation day (GD) 6 through 20 or pregnant rabbits from GD 6 through 18, there was no evidence of fetalmalformations or embryotoxicity in rats or rabbits at respective doses that achieved systemic exposures 48 to 58 timesthe exposure in patients treated with 50 mg etanercept once weekly (on an AUC basis with maternal subcutaneousdoses up to 30 mg/kg/day in rats and 40 mg/kg/day in rabbits). In a peri-and post-natal development study withpregnant rats that received etanercept during organogenesis and the later gestational period from GD 6 through 21,development of pups through post |
