Can biologic agents be given during pregnancy and breastfeeding?
TNF inhibitors and ustekinumab are FDA Pregnancy Classification B (old classification) medications. They can be used if clinically necessary for the mother’s health. It should be noted that only 4% of the maternal blood level of ETN is detected in the fetal circulation. Immunoglobulins do not cross placenta before 13 to 16 weeks of gestation, thus TNF inhibitors that are monoclonal antibodies should not cross the placenta until then. Recent data suggest that certolizumab pegol crosses the placenta much less than other monoclonal antibodies because it does not have a functional Fc fragment attributable to the pegylation and is, therefore, likely the safest anti-TNF agent that can be used throughout pregnancy, whereas the other TNF inhibitors should be stopped at the end of the second trimester. Animal and observational data support that the congenital malformation rate is not more than the 3% risk in the general population, and the incidence of serious or opportunistic infections in infants born to mothers with RA on biologics was similar to infants born to mothers with RA who did not receive biologics (4% versus 2.6%). Importantly, infants born to mothers who have received a TNF inhibitor (not certolizumab) throughout pregnancy should not receive live vaccines (rotavirus and BCG) until at least 5 to 6 months of age as a result of the TNF inhibitor crossing the placenta and remaining in the infant’s circulation for a prolonged period. Finally, only 4% of ETN gets into breast milk, whereas very little of the monoclonal TNF inhibitors get into breast milk because IgG antibodies are not transferred from the maternal circulation to breast milk in high amounts. Any biologic that does get into the breast milk will be destroyed by the infant’s digestive system and unlikely to be harmful. Therefore, breastfeeding is allowed in patients on TNF inhibitors.
All other biologic agents are FDA Pregnancy Classification C (old classification) medications. They have not been studied sufficiently and are therefore not recommended or should be used with caution during pregnancy. RTX has been reported to cause transient B-cell depletion in the fetus and infant when given to the mother during pregnancy. The outcome of pregnancies of patients who receive any biologic agent during pregnancy should be reported to the Organization of Teratology Information Specialists registry at 1-866-626-6847. There is also limited data on safety of breastfeeding with these biologics. However, if any biologic does get into the breast milk, it is likely destroyed by the infant’s digestive system.
