The Basics
What is Etanercept?
Used to reduce signs and symptoms of active arthritis, rheumatoid arthritis, or psoriatic arthritis, such as joint swelling, pain, tiredness, and duration of morning stiffness.
Brand names for Etanercept
Enbrel
How Etanercept is classified
Antirheumatic Agents, Dermatologic Agents, Gastrointestinal Agents
Etanercept During Pregnancy
Etanercept pregnancy category
Category N/ANote that the FDA has deprecated the use of pregnancy categories, so for some medications, this information isn’t available. We still think it’s useful to list historical info, however, given what a common proxy this has been in the past.
What we know about taking Etanercept while pregnant
Available studies with use of etanercept during pregnancy do not reliably support an association between etanercept and major birth defects. Clinical data are available from the Organization of Teratolog y Information Specialists (OTIS) Enbrel Pregnancy Registry in women with rheumatic diseases or psoriasis and a Scandinavian study in pregnant women with chronic inflammatory disease. Both the OTIS Registry and the Scandinavian study showed the proportion of liveborn infants with major birth defects was higher for women exposed to etanercept compared to diseased etanercept unexposed women. However, the lack of pattern of major birth defects is reassuring and differences between exposure groups (eg. disease severity) may have impacted the occurrence of birth defects (see Data). In animal reproduction studies with pregnant rats and rabbits, no fetal harm or malformations were observed with 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 Enbrel once weekly (see Data). All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the United States, about 2-4% 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 Enbrel is unknown. Risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed to Enbrel in utero [see Use In Specific Populations]. Data Human Data A prospective cohort pregnancy registry conducted by OTIS in the US and Canada between 2000 and 2012 compared the risk of major birth defects in liveborn infants of women with rheumatic diseases or psoriasis exposed to etanercept in 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 minor birth 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 the Danish (2004-2012) and Swedish (2006-2012) population based health 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 in etanercept-exposed patients compared to diseased etanercept unexposed patients, the lack of pattern of birth defects is reassuring and differences between exposure groups (e.g. disease severity) may have impacted the occurrence of birth defects. Three case reports from the literature showed that cord blood levels of etanercept at delivery, in infants born to women 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 rats from gestation day (GD) 6 through 20 or pregnant rabbits from GD 6 through 18, there was no evidence of fetal malformations or embryotoxicity in rats or rabbits at respective doses that achieved systemic exposures 48 to 58 times the exposure in patients treated with 50 mg Enbrel once weekly (on an AUC basis with maternal subcutaneous doses up to 30 mg/kg/day in rats and 40 mg/kg/day in rabbits). In a peri-and post-natal development study with pregnant rats that received etanercept during organogenesis and the later gestational period from GD 6 through 21, development of pups through post-natal day 4 was unaffected at doses that achieved exposures 48 times the exposure in patients treated with 50 mg Enbrel once weekly (on an AUC basis with maternal subcutaneous doses up to 30 mg/kg/day).
Taking Etanercept While Breastfeeding
What are recommendations for lactation if you're taking Etanercept?
Etanercept is minimally excreted into breastmilk and poorly absorbed by the infant, which would be expected because of its high molecular weight of approximately 150,000. However, long-term follow-up data on infants breastfed during maternal etanercept use are not available. The risk of adverse effects in older infants is not known, but thought to be unlikely.[1] Most experts feel that the drug is a low risk to the nursing infant and can be given during breastfeeding.[2][3][4][5][6][7]
Maternal / infant drug levels
Etanercept is minimally excreted into breastmilk and poorly absorbed by the infant, which would be expected because of its high molecular weight of approximately 150,000. However, long-term follow-up data on infants breastfed during maternal etanercept use are not available. The risk of adverse effects in older infants is not known, but thought to be unlikely.[1] Most experts feel that the drug is a low risk to the nursing infant and can be given during breastfeeding.[2][3][4][5][6][7]
Possible effects of Etanercept on milk supply
Relevant published information was not found as of the revision date.
Possible alternatives to Etanercept
(Psoriasis) Adalimumab, Infliximab, Phototherapy, Tretinoin; (Rheumatoid Arthritis) Adalimumab, Certolizumab Pegol, Infliximab.
List of References
Lactation sources: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK501922/1. Ostensen M, Eigenmann GO. Etanercept in breast milk. J Rheumatol. 2004;31(5):1017. Letter. PMID: 15124283
2. Hyrich KL, Verstappen SM. Biologic therapies and pregnancy: The story so far. Rheumatology (Oxford). 2014;53:1377-85. PMID: 24352337
3. Nguyen GC, Seow CH, Maxwell C et al. The Toronto Consensus Statements for the Management of IBD in Pregnancy. Gastroenterology. 2016;150:734-57. PMID: 26688268
4. van der Woude CJ, Ardizzone S, Bengtson MB et al. The second European evidenced-based consensus on reproduction and pregnancy in inflammatory bowel disease. J Crohns Colitis. 2015;9:107-24. PMID: 25602023
5. Flint J, Panchal S, Hurrell A et al. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Rheumatology (Oxford). 2016;55:1693-7. PMID: 26750124
6. Gotestam Skorpen C, Hoeltzenbein M, Tincani A et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis. 2016;75:795-810. PMID: 26888948
7. Amin M, No DJ, Egeberg A et al. Choosing first-line biologic treatment for moderate-to-severe psoriasis: What does the evidence say? Am J Clin Dermatol. 2018;19:1-13. PMID: 29080066
8. Murashima A, Watanabe N, Ozawa N et al. Etanercept during pregnancy and lactation in a patient with rheumatoid arthritis: drug levels in maternal serum, cord blood, breast milk and the infant’s serum. Ann Rheum Dis. 2009;68:1793-4. PMID: 19822717
9. Berthelsen BG, Fjeldsoe-Nielsen H, Nielsen CT, Hellmuth E. Etanercept concentrations in maternal serum, umbilical cord serum, breast milk and child serum during breastfeeding. Rheumatology (Oxford). 2010;49:2225-7. PMID: 20581374
10. Keeling S, Wolbink GJ. Measuring multiple etanercept levels in the breast milk of a nursing mother with rheumatoid arthritis. J Rheumatol. 2010;37:1551. PMID: 20595298
11. Dall’ara F, Reggia R, Bazzani C et al. Safety of anti-TNF alfa agents during pregancy and breastfeeding: longterm follow up of exposed children in a case-series of mothers with chronic arthritides. Ann Rheum Dis. 2016;75 (Suppl 2):493. Abstract. DOI: doi:10.1136/annrheumdis-2016-eular.4123
Disclaimer: This material is provided for educational purposes only and is not intended for medical advice, diagnosis, or treatment. Consult your healthcare provider with any questions.
