Golimumab is detectable in fetal circulation

Last Updated: 2018-12-20

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - Golimumab was detected in the circulation of a fetus whose mother was being treated with the drug for ulcerative colitis, according to a case study from France.

"In this report, we demonstrated that golimumab was detectable in the fetal circulation after prolonged exposure, with a significant accumulation," researchers write in a letter to the editor in the Journal of Crohn's and Colitis, online November 15.

"Golimumab was found in the baby's blood but there was no untoward consequence to the baby. These are not surprising findings as other monoclonal antibodies, such as infliximab and adalimumab, have similar findings and safety," Dr. Miguel Regueiro, chair of the department of gastroenterology and hepatology at Cleveland Clinic in Ohio, told Reuters Health by email. He was not involved in the report.

Dr. Paul Berveiller of Centre Hospitalier Intercommunal de Poissy-Saint Germain and colleagues reported the case of a 28-year-old nulliparous woman with ulcerative colitis who became pregnant. Before her pregnancy, she had been treated with mesalazine and golimumab 100 mg twice a month, and she continued to be treated with golimumab throughout her pregnancy.

The woman's pregnancy was normal and she delivered a healthy 2,805 g (6 lb) male infant at 37+6 weeks, three days after her last golimumab dose.

Immediately after the delivery, golimumab concentrations reached 6.6 ug/mL in the mother's plasma and 8 ug/mL in the neonate's cord blood (121% of maternal concentrations). The pediatric team advised the mother that the baby should not be breastfed or receive any live vaccine during his first year.

The researchers found no complications over seven months of follow-up.

Dr. Adam C. Ehrlich, an assistant professor of medicine and co-medical director of the Inflammatory Bowel Disease Program at the Lewis Katz School of Medicine at Temple University in Philadelphia, said, "I was not surprised to see golimumab present in the fetus at higher concentrations than in the mother. Similar to infliximab and adalimumab, the Fc portion of the antibody is retained and allows active transport across the placenta. The exception is certolizumab, where a lack of the Fc portion results in minimal transfer to the fetus."

"The data for infliximab and adalimumab suggest no significant adverse outcomes in the child; that seems to be true in this case as well," Dr. Ehrlich, who was not involved in the study, told Reuters Health by email.

The authors note that the U.S. Food and Drug Administration (FDA) classifies anti-tumor necrosis factor (TNF)-alpha monoclonal antibodies (AT-MAB) as Category B for use during pregnancy.

"However, clinical data on fetal safety of AT-MAB were only obtained from patients receiving adalimumab, infliximab and certolizumab," they note.

"MAB are actively transported across the placenta, and fetal immunoglobulin concentrations increase logarithmically during pregnancy. IgG1-MAB have a prolonged half-life in the neonate, and usually disappear from the child's serum within the first 6 months of life," they explain.

"Although we have some data about the risks of other anti-TNF therapies, the lack of data regarding golimumab made this an important finding to report," Dr. Ehrlich said. "These findings add to the body of literature suggesting that, while anti-TNF drugs are often present in the infant after childbirth, they generally do not cause complications."

Dr. Ehrlich stressed that this study involved only one mother and infant, which limits its applicability. "We should not be drawing major conclusions."

Dr. Regeuiro noted that patients with inflammatory bowel disease can be young and otherwise healthy, so female patients with ulcerative colitis who become pregnant are common.

"It is most important to continue medications in pregnancy to control inflammatory bowel disease and avoid flares. Aside from certain drugs, e.g., methotrexate and tofacitinib, we recommend continuing medications for inflammatory bowel disease," he advised.

"It's important to not give the baby a live vaccine in the first few months of life," he cautioned.

The researchers advise that providers discuss with their patients the potential benefits and harms, and the uncertainties, of taking golimumab during pregnancy.

They note that neonatal and long-term safety data about golimumab are scarce, and they recommend further study to investigate the effects of the drug during pregnancy.

The study received no funding, and the authors reported no ties to Janssen Biotech, which markets golimumab as Simponi.

Dr. Berveiller did not respond to requests for comments.

SOURCE: https://bit.ly/2PPINqU

J Crohns Colitis 2018.