Immunologic Agent (Immunosuppressant)
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Low Risk Contraindicated—1st Trimester (If Combined with Mycophenolate)
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible Contraindicated (If Combined with Mycophenolate)
PREGNANCY SUMMARY
No reports describing the use of belatacept in human pregnancy have been located. The animal data suggest low risk but the absence of human pregnancy experience prevents a better assessment. However, belatacept is used in combination with basiliximab induction, mycophenolate, and corticosteroids, and the latter two agents are known human teratogens (see Mycophenolate and Prednisone). Nevertheless, rejection of a transplanted organ has serious consequences for the mother and her pregnancy. Therefore, if indicated, the drug should not be withheld because of pregnancy but the woman should be informed of the potential risk to her embryo–fetus. In addition, physicians are encouraged to register pregnant patients in the National Transplant Pregnancy Registry by calling 1-877-955-6877.
FETAL RISK SUMMARY
Belatacept, a selective T-cell costimulation blocker given as an IV infusion, is a protein that is fused to a portion of human immunoglobulin G1 antibody. The parent molecule, abatacept, differs from belatacept by two amino acids. Belatacept is indicated for prophylaxis of organ rejection in adult patients receiving a kidney transplant and is used in combination with basiliximab induction, mycophenolate mofetil, and corticosteroids. Although information on the metabolism of belatacept was not provided by the manufacturer, the terminal half-life was about 8–10 days depending on the dose (1).
Reproduction studies have been conducted in rats and rabbits. In these species, no teratogenicity was observed at exposures that were 16 and 19 times the maximum recommended human dose during the first month of treatment based on AUC (MRHD). In rats, daily belatacept during gestation and throughout the lactation period was associated with maternal toxicity (infections) in a small percentage of dams at doses that were ≥3 times the MRHD. This toxicity resulted in increased pup mortality (up to 100% in some dams), but there were no abnormalities or malformations in surviving pups. The in vitro data indicate that belatacept has lower potency in rodents than in humans, but the in vivo difference in potency is unknown. Thus, the relevance of the rat toxicities to humans and the significance of the magnitude of the relative exposures to humans are unknown (1).
Carcinogenicity studies have not been conducted with belatacept but have been with abatacept, the more active analog in rodents. Weekly SC injections of abatacept in mice were associated with increases in the incidences of malignant lymphomas and mammary gland tumors (in females). The clinical significance of these findings is unknown because the mice were infected with endogenous murine leukemia and mouse mammary tumor viruses which are associated with an increased incidence of lymphomas and mammary gland tumors, respectively. However, cases of posttransplant lymphoproliferative disorder (a premalignant or malignant proliferation of B lymphocytes) have been reported in clinical trials. Genotoxicity studies have not been conducted with belatacept because they are not required for protein therapeutics. No effects on male or female fertility were observed (1).
It is not known if belatacept crosses the human placenta. The protein is known to cross the placenta of animals. The molecular weight (about 90,000) suggests that transfer of the agent across the placenta will be limited, but the elimination half-life will place it at the maternal–fetal interface for a prolonged period. Moreover, the parent molecule, abatacept crosses the placenta. In addition, immunoglobulin G crosses the placenta, especially in the latter portion of pregnancy and belatacept is an immunoglobulin G antibody. Therefore, exposure of the embryo and/or fetus should be expected.
BREASTFEEDING SUMMARY
No reports describing the use of belatacept during human lactation have been located. The molecular weight (about 90,000) suggests that excretion of the agent into breast milk will be limited, but the terminal half-life is very long (8–10 days). Immunoglobulin G is excreted into colostrum and belatacept is an immunoglobulin G antibody. Moreover, belatacept is used in combination with basiliximab induction, mycophenolate mofetil, and corticosteroids. Basiliximab and corticosteroids appear to be compatible with breastfeeding (see Basiliximab and Prednisone), but mycophenolate is contraindicated (see Mycophenolate). Thus, although belatacept alone is probably compatible, if taken with mycophenolate breastfeeding should be avoided.
Reference
1.Product information. Nulojix. Bristol-Myers Squibb, 2011.