Immunologic Agent (Immunomodulator)
PREGNANCY RECOMMENDATION: No Human Data—Probably Compatible
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of belimumab in human pregnancy have been located. Teratogenicity was not observed in cynomolgus monkeys. This species was chosen because belimumab binds cynomolgus monkey and human B-lymphocyte stimulator protein with equal affinity. Compared with controls, an increased risk of fetal death was observed at the lowest but not the highest dose. An increased risk of infant death compared with controls also was observed with both doses. A dose relationship was not apparent in either outcome and the rates were consistent with historical control data for macaques. No other forms of developmental toxicity were observed in the offspring. If belimumab is used in pregnancy, patients should be informed of the lack of human pregnancy experience.
FETAL RISK SUMMARY
Belimumab is a human immune globulin G1 lambda (IgG1λ) monoclonal antibody that is a specific inhibitor of soluble human B-lymphocyte stimulator protein. It is indicated for the treatment of adult patients with active, autoantibody-positive, systemic lupus erythematosus who are receiving standard therapy. The terminal half-life is 19.4 days (1).
Reproduction studies have been conducted in pregnant cynomolgus monkeys with IV infusion doses of 0 (controls), 5, and 150 mg/kg (the highest dose was about 9 times the anticipated maximum human exposure based on AUC) given every 2 weeks from gestation day 20 to 150. The antibody was not associated with direct or indirect teratogenicity. Skeletal and cardiac variations were observed but the rates were within historical control rates. Fetal deaths were observed in 14%, 24%, and 15%, respectively, and infant deaths were observed in 0%, 8%, and 5%, respectively. The cause of the deaths was not known, but the incidences were considered incidental as they were comparable with historical control data for macaques. After cessation of treatment, B-cell numbers recovered about 1 year postpartum in adult monkeys and by 3 months of age in offspring (1,2).
Neither the carcinogenic potential nor the mutagenic potential has been evaluated. The effects on male and female fertility in animals have not been studied (1).
Although the molecular weight is high (about 147,000), belimumab crossed the placenta late in gestation in cynomolgus monkeys as expected for an immune globulin antibody (2). Because the human and monkey placentas are similar, exposure of the human fetus probably occurs.
BREASTFEEDING SUMMARY
No reports describing the use belimumab during human lactation have been located. Although the molecular weight is high (about 147,000), belimumab was excreted into the milk of cynomolgus monkeys (1). In addition, because maternal antibodies are excreted into breast milk, the presence of belimumab in milk should be expected. The effect of this exposure on a nursing infant is unknown.
References
1.Product information. Benlysta. Human Genome Sciences, 2011.
2.Auyeung-Kim DJ, Devalaraja MN, Migone TS, Cai W, Chellman GJ. Developmental and peri-postnatal study in cynomolgus monkeys with belimumab, a monoclonal antibody directed against B-lymphocyte stimulator. Reprod Toxicol 2009;28:443–55.