Belimumab

The Basics

What is Belimumab?

Used to treat active systemic lupus erythematosus (SLE) in adults.

Brand names for Belimumab

Benlysta

How Belimumab is classified

Antibodies – Monoclonal

Belimumab During Pregnancy

Belimumab pregnancy category

Category N/ANote that the FDA has deprecated the use of pregnancy categories, so for some medications, this information isn’t available. We still think it’s useful to list historical info, however, given what a common proxy this has been in the past.

What we know about taking Belimumab while pregnant

There are no adequate and well-controlled clinical studies using BENLYSTA in pregnant women. Immunoglobulin G (IgG) antibodies, including BENLYSTA, can cross the placenta. Because animal reproduction studies are not always predictive of human response, BENLYSTA should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. Women of childbearing potential should use adequate contraception during treatment with BENLYSTA and for at least 4 months after the final treatment., Nonclinical reproductive studies have been performed in pregnant cynomolgus monkeys receiving belimumab at doses of 0, 5 and 150 mg/kg by intravenous infusion (the high dose was approximately 9 times the anticipated maximum human exposure) every 2 weeks from gestation day 20 to 150. Belimumab was shown to cross the placenta. Belimumab was not associated with direct or indirect teratogenicity under the conditions tested. Fetal deaths were observed in 14%, 24% and 15% of pregnant females in the 0, 5 and 150 mg/kg groups, respectively. Infant deaths occurred with an incidence of 0%, 8% and 5%. The cause of fetal and infant deaths is not known. The relevance of these findings to humans is not known. Other treatment-related findings were limited to the expected reversible reduction of B cells in both dams and infants and reversible reduction of IgM in infant monkeys. B-cell numbers recovered after the cessation of belimumab, 294 treatment by about 1 year post-partum in adult monkeys and by 3 months of age in infant, 295 monkeys. IgM levels in infants exposed to belimumab in utero recovered by 6 months of age. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to BENLYSTA during pregnancy. Healthcare professionals are encouraged to register patients by calling 1-877-681-6296. Risk Summary Available data on use of BENLYSTA in pregnant women, from observational studies, published case reports, and postmarketing surveillance, are insufficient to determine whether there is a drug-associated risk for major birth defects or miscarriage. There are risks to the mother and fetus associated with SLE (see Clinical Considerations). Monoclonal antibodies, such as belimumab, are actively transported across the placenta during the third trimester of pregnancy and may affect immune response in the in utero-exposed infant (see Clinical Considerations). In an animal combined embryo-fetal and pre- and post-natal development study with monkeys that received belimumab by intravenous administration, there was no evidence of fetal harm with exposures approximately 9 times (based on intravenous administration) and 20 times (based on subcutaneous administration) the exposure at the maximum recommended human dose (MRHD). Belimumab-related findings in monkey fetuses and/or infants included reductions of B-cell counts, reductions in the density of lymphoid tissue B-lymphocytes in the spleen and lymph nodes, and altered IgG and IgM titers. The no-adverse-effect-level (NOAEL) was not identified for these findings; however, they were reversible within 3 to 12 months after the drug was discontinued (see Data). Based on animal data and the mechanism of action of belimumab, the immune system in infants of treated mothers may be adversely affected. It is unknown, based on available data, whether immune effects, if identified, are reversible [see CLINICAL PHARMACOLOGY]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Pregnant women with SLE are at increased risk of adverse pregnancy outcomes, including worsening of the underlying disease, premature birth, miscarriage, and intrauterine growth restriction. Maternal lupus nephritis increases the risk of hypertension and preeclampsia/eclampsia. Passage of maternal autoantibodies across the placenta may result in adverse neonatal outcomes, including neonatal lupus and congenital heart block. Fetal/Neonatal Adverse Reactions Monoclonal antibodies are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester. Risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed to BENLYSTA in utero. Monitor an infant of a treated mother for Bcell reduction and other immune dysfunction . Data Animal Data In a combined embryo-fetal and pre- and post-natal development study, pregnant cynomolgus monkeys received belimumab at intravenous doses of 0, 5, or 150 mg/kg every 2 weeks from confirmation of pregnancy at Gestation Days (GD) 20 to 22, throughout the period of organogenesis (up to approximately GD 50), and continuing to either the day of scheduled cesarean section (GD 150 [late third trimester]) or the day of parturition. There was no evidence of maternal toxicity, effects on embryofetal and infant survival, or structural abnormalities at exposure approximately 9 times the MRHD of 10 mg/kg intravenously or 20 times the MRHD of 200 mg subcutaneously (on an AUC basis with maternal animal intravenous doses up to 150 mg/kg). Belimumab-related findings in mothers included reductions of immature and mature B-cell counts and in fetuses and/or infants included reductions of immature and mature B-cell counts, reductions in the density of lymphoid tissue B-lymphocytes in the spleen and lymph nodes, reduced spleen weights, increased IgG titers, and reduced IgM titers. B-cell counts in infant monkeys exposed to belimumab in utero recovered by 3 months of age and in mothers after 1 year. IgG and IgM levels in infant monkeys recovered by 6 months of age and the reductions in B-lymphocytes in the lymph nodes and spleen were reversed by 1 year of age. Belimumab crossed the placenta, as it was detected in fetal cord blood and amniotic fluid on GD 150.

Taking Belimumab While Breastfeeding

What are recommendations for lactation if you're taking Belimumab?

No information is available on the clinical use of belimumab during breastfeeding. Because belimumab is a large protein molecule with a molecular weight of 147,000, the amount in milk is likely to be very low and absorption is unlikely because it is probably destroyed in the infant’s gastrointestinal tract. If belimumab is required by the mother, it is not a reason to discontinue breastfeeding.[1] Until more data become available, belimumab should be used with caution during breastfeeding, especially while nursing a newborn or preterm infant. Belimumab is a human immunoglobulin G1 (IgG1) lambda antibody. Holder pasteurization (62.5 degrees C for 30 minutes) decreases the concentration of endogenous immunoglobulin G by up to 79%.[2][3] A study of 67 colostrum samples that underwent Holder pasteurization found that IgG amounts decreased by 34 to 40%. Specific IgG subclasses decreased by different amounts, with IgG1 activity decreasing by about 37%.[4] None of the studies measured IgG activity.

Maternal / infant drug levels

No information is available on the clinical use of belimumab during breastfeeding. Because belimumab is a large protein molecule with a molecular weight of 147,000, the amount in milk is likely to be very low and absorption is unlikely because it is probably destroyed in the infant’s gastrointestinal tract. If belimumab is required by the mother, it is not a reason to discontinue breastfeeding.[1] Until more data become available, belimumab should be used with caution during breastfeeding, especially while nursing a newborn or preterm infant. Belimumab is a human immunoglobulin G1 (IgG1) lambda antibody. Holder pasteurization (62.5 degrees C for 30 minutes) decreases the concentration of endogenous immunoglobulin G by up to 79%.[2][3] A study of 67 colostrum samples that underwent Holder pasteurization found that IgG amounts decreased by 34 to 40%. Specific IgG subclasses decreased by different amounts, with IgG1 activity decreasing by about 37%.[4] None of the studies measured IgG activity.

Possible effects of Belimumab on milk supply

Relevant published information was not found as of the revision date.

Possible alternatives to Belimumab

None listed