Immunologic (Fusion Protein)
PREGNANCY RECOMMENDATION:Limited Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION:Potential Toxicity
A few studies have been located that describe the use of abatacept during human pregnancy. The largest involved patients reported to the manufacturer, which may produce a bias toward the reporting of poor outcomes. In 132 exposed pregnancies (excluding elective terminations), there were 44 (33%) spontaneous losses and 2 pregnancies lost to follow-up. Of the 86 live births, there were 6 (7%) major anomalies, and all were different (no pattern). The spontaneous loss rate is high, but many of these pregnancies were on numerous other drugs, including methotrexate. Abatacept has been shown to cross the placenta. This is consistent with the drug having the Fc fragment of an immunoglobulin G (IgG)1 antibody. Therefore, some fetal exposure will occur. However, this limited human pregnancy experience prevents a complete assessment of the embryofetal risk. Animal data did not show any embryofetal toxicity or malformations in three species at doses of less than 10 times the RHD in one species and more than 10 times the RHD in the other two. Using this drug during pregnancy should be based on the pros and cons of the mother’s clinical need for treatment versus any potential fetal risk that might occur from exposure. It is contraindicated if abatacept is combined with methotrexate or leflunomide. There is a pregnancy exposure registry that monitors pregnancy outcomes in women using this drug. Health care providers are encouraged to call the Orencia Pregnancy Exposure Registry at 1-877-311-8972.
Two studies have been located that described the use of abatacept during human lactation. A total of three women using the drug had breast milk samples tested. The peak levels ranged from 100 to 256 ng/mL, and the trough levels ranged from 50 to 170 ng/mL. The calculated RIDs were all below 3%. In addition, no adverse effects on the neonates were reported. It is known that the Fc fragment of IgG antibodies facilitates transport, so some of the drug may be found in human breast milk. Regardless, if any of this fusion protein were to be ingested through breastfeeding, it would probably be digested in the infant’s gastrointestinal tract and not be absorbed. Despite this, due to a concern for potential serious adverse effects that might be seen in a breastfed infant, the manufacturer recommends that women not breastfeed while being treated with this drug. However, breastfeeding while using this drug should be based on the mother’s clinical need for treatment versus any potential infant risks that might occur. If used, the infant should be monitored for the most common reported adult side effects of nausea (leading to irritability) and upper respiratory tract infection.