Postpartum disease flares are common and very challenging for new moms with rheumatic diseases. “They have a new infant, which requires their attention, their hands, and their being able to be awake and to move in the middle of the night and the early morning hours,” said Megan E.B. Clowse, associate professor at Duke University School of Medicine. “Treatment during this period is important to these women.”
Dr. Clowse was presenting “Evaluating Transfer of Certolizumab Pegol into Breast Milk: Results from a Prospective, Postmarketing, Multicenter Pharmacokinetic Study” at the 2016 ACR/ARHP Annual Meeting in Washington, D.C.
“This is the first sponsored study to collect breast milk samples and to assess the certolizumab pegol concentrations in order to estimate the average daily infant dose that a breastfed infant would receive when the mother is taking this drug,” she said.
Most drugs come with warnings against taking them while pregnant and nursing to protect the baby. But for moms with ankylosing spondylitis, Crohn’s disease, psoriatic arthritis and rheumatoid arthritis, taking certolizumab pegol (CZP) is important.
Prior research suggested that there is a limited transfer of anti-tumor necrosis factor (TNF) drugs into breast milk, “but this data is limited because of small sample size,” Dr. Clowse said. “They weren’t planned-out studies. They were just women who happened to be lactating, and they got samples randomly after drug dosing. They generally used non-validated methods to assess the amount of drug in breast milk.”
Very low levels of immunoglobulin G (IgG) transfer into human breast milk, and research has shown that the infant’s digestive tract can absorb the antibodies.
“We think, however, that certolizumab pegol, if it were to be in breast milk, would have potentially less chance of getting into the infant’s blood,” Dr. Clowse said. Since it is a protein, certolizumab pegol should largely degrade in the infant’s gut, she said, and it shouldn’t transfer across the placenta. In fact, that’s what the study found.
The study relied on a “really carefully thought out” enzyme-linked immunosorbent assay (ELISA) test to detect drug levels in breast milk, Dr. Clowse said. “It was 10 times more sensitive than any of the prior assays used to identify CZP.”
To measure drug absorption, Dr. Clowse and her colleagues used two different measures: the “average daily infant dose,” which is an estimation of the dose an infant would be assumed to ingest, and the “relative infant dose,” which is the potential, expressed as a percentage, of the infant’s exposure to the maternal dose.
“An RID of less than 10 percent — meaning the infant would be receiving less than 10 percent of the maternal dose — is thought to be of little concern for infant well-being,” Dr. Clowse said.
Of the 18 mothers in the study — one was dropped during screening — there was an average age of just above 33-and-a-half. Seven had rheumatoid arthritis, three had psoriatic arthritis, two had axial spondyloarthritis/ankylosing spondylitis and five had Crohn’s disease. Of the 17 babies, 13 were younger than 6 months old at the time of the mom’s first sample; two were between 6 and 12 months; and another two were between a year and 18 months.
When Dr. Clowse and colleagues crunched the numbers, they found that four of the moms were below the limit of quantification (less than .032 micrograms per milliliter) for CZP in their breast milk during every test. Two patients had less than three times the limit of quantification, and 11 had less than twice the limit. Some of the latter group, however, were only above twice the limit by .001. “Extraordinarily close to that line,” Dr. Clowse said.
Even in the group whose CZP levels were highest, the entire group was well below three times the lower limit. “To be three times higher, you had to be .096,” Dr. Clowse said. The highest number registered in the study was .076, barely twice the lower limit.
“A grownup adult taking CZP herself would be expected to have a rate around 15.7,” she said. “That is far greater than the levels that we are measuring here.”
The study found an average level of .04285, an average daily infant dose of .003503 milligrams per kilogram per day; and a relative infant dose of .125 percent of the expected maternal dose. All those numbers are encouraging — .125 is well below the 10 percent cutoff for infant safety — and the side effects that both moms and babies had were those that would be expected of women on CZP breastfeeding.
Or as Dr. Clowse and colleagues put it in the abstract, “These findings are reassuring and imply that continuation of CZP treatment is compatible with breastfeeding.”