Etanercept concentrations in maternal serum, umbilical cord serum, breast milk and child serum during breastfeeding

Sir, Etanercept is a TNF inhibitor that has been approved by the FDA for the treatment of RA, AS, PsA, chronic moderate-to-severe psoriasis and polyarticular juvenile idiopathic arthritis. The use of TNF inhibitors in fertile women is increasing and there is a need for more knowledge about the safety of these drugs during pregnancy and breastfeeding. Only two previous studies have investigated etanercept in breast milk finding low concentrations [1, 2]. Safety during pregnancy and breastfeeding is still a matter of debate and the general recommendation is to discontinue TNF inhibitors during pregnancy and breastfeeding if possible [3]. To further elucidate this area, we studied the transmission of etanercept from mother to child at delivery and during breastfeeding. The current case describes a 34-year-old female diagnosed with AS. Before pregnancy, she had been treated with etanercept injections 25 mg s.c. once to twice a week for 4 years. During the first trimester of pregnancy, etanercept dose was reduced to 25 mg once every second week and then due to progression of symptoms increased to 25 mg once a week during the second and third trimester. A healthy baby boy was born at 40 weeks gestational age. The mother decided to continue etanercept 25 mg s.c. once a week during breastfeeding (post partum Days 8, 13, 21, 27, 34, 40 and 47). Etanercept concentrations (Table 1) were measured with fluid-phase RIA [4]. Etanercept concentrations from maternal serum and umbilical cord (arterial) serum were measured at the time of delivery. Furthermore, maternal serum and breast milk concentrations were measured from Day 40 to Day 47 post partum and serum concentrations from the child (weight 4900 g) on Days 41–43. Blood and breast milk samples were taken prior to etanercept injection on Days −7, 40 and 47. The child's estimated average daily milk intake was ∼800 ml (post partum Days 41–43) divided between 400 ml breast milk and 400 ml milk substitute. Concentration (ng/ml) of etanercept in maternal serum, breast milk, umbilical cord and child serum aLower detection limit in serum 4 ng/ml. bLower detection limit in breast milk 2 ng/ml. cBlood from umbilical cord. x: Day of etanercept injection. Concentration (ng/ml) of etanercept in maternal serum, breast milk, umbilical cord and child serum aLower detection limit in serum 4 ng/ml. bLower detection limit in breast milk 2 ng/ml. cBlood from umbilical cord. x: Day of etanercept injection. The mother's BMI was 33 on Day −7 and 30 on Day 40. The maternal serum concentration was 540 ng/ml at delivery and ranged from 840 to 2000 ng/ml post partum. The etanercept concentration ratio between maternal serum and umbilical cord serum was 14 : 1 at delivery supporting low transplacental transmission. Breast milk concentrations were very low (≤5 ng/ml). These results are consistent with the findings by Murashima et al. [1] when considering the higher etanercept dosage (25 mg twice a week) in that study. Etanercept could not be detected in the child's serum (lower detection limit 4 ng/ml). No etanercept antibodies were detected in maternal serum. The pregnancy was uncomplicated and the baby was healthy supporting that etanercept was safe to use for both mother and child, whereas any long-term effects are still unknown. Our results show that the unborn child was exposed to low concentrations of etanercept through transplacental transmission late in pregnancy. Maternal serum concentrations were consistent with previously published concentrations in patients with AS [5]. Breast milk concentrations were comparable to that (3.5 ng/ml) published by Murashima et al. [1] but much lower than values found by Ostensen et al. (25–75 ng/ml) [2]. Apart from differences in sample collection, etanercept analysis methods and dosage (25 mg twice a week), the mother in Ostensen's study was lactating but not breastfeeding [2]. Furthermore, her milk production ceased during the study period. Not surprisingly, we did not detect etanercept in the breastfed child's serum during the second month post partum. Thus, etanercept proved to be safe in our case for both mother and child during pregnancy and breastfeeding with low transplacental etanercept transmission at birth, very low levels of etanercept in breast milk and no detected absorption by the child. Concentration measurements during pregnancy and breastfeeding are encouraged to further clarify the transmission of etanercept from mother to child and the safety profile of the drug. This study was approved by the ethics committees in Copenhagen and The Danish Data Protection Agency. Informed patient consent was obtained for this study. Funding: The study was financed by Statens Serum Institut, Copenhagen, Denmark. Disclosure statement: The authors have declared no conflicts of interest.