Drugs in Pregnancy and Lactation: Tenth Edition

GOLIMUMAB

Immunologic Agent (Immunomodulator)

PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Low Risk Contraindicated (if combined with methotrexate)

BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible Contraindicated (if combined with methotrexate)

PREGNANCY SUMMARY

No reports describing the use of golimumab in human pregnancy have been located. The animal data from one species suggest that the embryo–fetal risk is low. However, the lack of human pregnancy experience prevents a full assessment of the risk. There is some similarity between the action of immunomodulators with antitumor necrosis factor alpha (TNFα) activity and the human teratogen thalidomide, a drug that also decreases the activity of TNFα (see Thalidomide). However, decreased production of TNFα may not be a primary cause of the teratogenicity of thalidomide. Theoretically, TNFα antagonists could interfere with implantation and ovulation, but this has not been shown clinically (1). If golimumab is indicated in a pregnant woman, she should be informed of the absence of human pregnancy data. Moreover, until adequate human data are available, the safest course is to avoid the drug during organogenesis (20–55 days after conception or 34–69 days from the first day of the last menstrual period).

FETAL RISK SUMMARY

Golimumab is a human IgG1k monoclonal antibody that blocks human TNFα. TNFα is a pro-inflammatory cytokine with a central role in inflammatory processes. Golimumab is in the same subclass of immunomodulators as adalimumab, certolizumab pegol, etanercept, and infliximab that block TNF. It is indicated, in combination with methotrexate, for the treatment of adult patients with moderately to severely active rheumatoid arthritis. Golimumab also is indicated, either alone or with methotrexate, for the treatment of adult patients with active psoriatic arthritis and, alone for the treatment of adult patients with active ankylosing spondylitis. The median terminal half-life is about 2 weeks (2).

Reproduction studies have been conducted in monkeys. Pregnant monkeys were given twice-weekly SC doses during the 1st trimester that were up to 300 times the maximum recommended human dose based on weight. No evidence of maternal or fetal harm or developmental defects was observed. The drug crossed the placenta as indicated by its presence in umbilical cord blood obtained at the end of the 2nd trimester. When monkeys were given twice-weekly SC doses during the 2nd and 3rd trimesters, no evidence of maternal or neonatal harm was noted. The doses produced maternal and neonatal exposures that were 860 and 310 times, respectively, the maximal steady state human blood levels. This exposure during pregnancy and lactation had no effect on the development and maturation of the immune system in offspring (2,3).

Studies for neither carcinogenicity nor mutagenicity have been conducted with golimumab. A study in mice using an analogous anti-mouse TNFα antibody showed no impairment of fertility (2).

It is not known if golimumab crosses the human placenta. The molecular weight (about 150,000–151,000) is high, but immunoglobulin G crosses the placenta late in pregnancy (see Immune Globulin Intravenous). Placental transfer of IgG was a function of dose, as well as gestational age. Moreover, golimumab crossed to the fetus in monkeys and, because the placentas in monkeys are similar to those in humans, the antibody should be expected to cross to the human fetus.

BREASTFEEDING SUMMARY

No reports describing the use of golimumab during human lactation have been located. It is not known if the antibody is excreted into breast milk. The molecular weight (about 150,000–151,000) is high, but the terminal half-life is very long (about 2 weeks). Because immunoglobulins are excreted into milk, exposure of a nursing infant should be expected. The effect of this exposure is unknown, but serious infections have been observed in human adults treated with golimumab. However, exposure during lactation had no effect on the development and maturation of the immune system in monkey offspring (3). Nevertheless, if a woman elects to nurse her infant while receiving this agent, close observation of the infant for signs and symptoms of infection should be considered.

References

1.Khanna D, McMahon M, Furst DE. Safety of tumor necrosis factor-α antagonists. Drug Saf 2004;27:307–24.

2.Product information. Simponi. Centocor Ortho Biotech, 2009.

3.Martin PL, Oneda S, Treacy G. Effects of an anti-TNF-α monoclonal antibody, administered throughout pregnancy and lactation, on the development of the macaque immune system. Am J Reprod Immunol 2007;58:138–49.



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