Duke Health Referring Physicians


Study Results Show Minimal to No Transfer of Certolizumab Pegol Into Breast Milk

Mothers who breastfeed while taking certolizumab pegol transfer very low doses of the medication into their breast milk, according to new research. These findings should be reassuring to nursing mothers who are concerned about the safety of breastfeeding during treatment with certolizumab pegol.

Laura Shaughnessy, PhD, of UCB Biosciences in Raleigh, NC, presented results from the prospective Concentration of Certolizumab Pegol in Mature Breast Milk of Lactating Mothers (CRADLE) trial at the 37th Annual Pregnancy Meeting of the Society for Maternal Fetal Medicine held January 23 to 28, 2017, in Las Vegas, NV. Megan E.B. Clowse, MD, of the Division of Rheumatology and Immunology at Duke University, was a coinvestigator of the CRADLE study.

“Women with chronic inflammatory diseases experience a lot of uncertainty around the safety of their treatment when they are having babies and considering breastfeeding,” Shaughnessy said. “When patients are considering whether it is in their best interest to take a drug while breastfeeding, it is important to have access to data to help make that decision.”

The CRADLE study was designed to measure the concentration of certolizumab pegol in breast milk among lactating mothers who were taking the anti-tumor necrosis factor agent for approved indications.

The multicenter study enrolled 18 women who were at least 6 weeks postpartum after delivering full-term infants. All of the mothers made the decision to breastfeed while taking certolizumab pegol prior to and independently from their decision to participate in the study. Although 18 women enrolled, only 17 contributed milk samples for the pharmaceutical analysis. All 18 mothers and infants were included in the safety assessment.

The average age of the participants was 33.7 years (Table 1). The indications for anti-tumor necrosis factor included inflammatory rheumatic diseases, such as rheumatoid arthritis and axial spondyloarthritis in 12 patients (70%) and Crohn disease in 5 patients (30%).

Table 1. Baseline Characteristics of Mothers and Infants

Characteristic All Mothers (N = 18)
Maternal demographics
Mean age, y 33.7 y
Mean body mass index, kg/m² 23.6
Maternal indication for certolizumab pegol treatment, na
Inflammatory rheumatic disease 12
Crohn disease 5
Infant age at time of mother’s first breast milk sample collection,
mo (%)
≤ 6 76.5
> 6 to ≤ 12 11.8
> 12 to ≤ 18 11.8

aIndication missing for 1 participant.

After achieving a steady state with at least 3 doses, women taking certolizumab pegol 200 mg every 2 weeks (n = 16) contributed milk samples on days 0, 2, 4, 6, 8, 10, 12, and 14 of each dosing period. One woman receiving certolizumab pegol 400 mg every 4 weeks contributed an additional sample on treatment day 28.

Researchers measured drug levels in breast milk using a new and highly sensitive enzyme-linked immunosorbent assay specific for certolizumab pegol. The assay has a lower limit of quantification of 0.032 μg/mL, which is 10-fold lower than assays utilized in prior pharmacokinetic studies of certolizumab pegol.

The results showed very low concentrations of certolizumab pegol in breast milk (Table 2). Certolizumab pegol was below the limit of detection in 56% of the samples collected from all of the women. In addition, the drug was undetectable in all of the samples collected from 4 of the 17 study participants.

Table 2. Pharmacokinetics of Certolizumab Pegol in Breast Milk

Variable Median Range
Maximum observed concentration in breast milk collected from mothers taking certolizumab pegol 200 mg every 2 wk (n = 16), µg/mL 0.0485 BLQ to 0.0758
Average daily infant dose (n = 17), mg/kg/d 0.0035 0.000-0.0104
Relative infant dose (n = 13), % 0.15 0.04-0.30

BLQ = below lower limit of quantification (< 0.032 μg/mL).

Across all samples, the median maximum observed concentration of certolizumab pegol was 0.0485 µg/mL. Given the average concentration of the drug in breast milk, infants were receiving a very low dose of medication. The median average daily infant dose was 0.0035 mg/kg/day, which is equivalent to a relative infant dose of 0.15% of the adult dose (range, 0.04%-0.30%). Relative infant doses below 10% are considered to be safe for infants.

In the safety analysis, 8 of 18 infants (44%) experienced a total of 11 adverse events (AEs). The most common AEs in infants were nasopharyngitis (n = 4) and upper respiratory tract infection (n = 2). Overall, the infants exposed to certolizumab pegol via breast milk experienced AEs of the same type and rate that would be expected in unexposed infants of a similar age. Among the 18 mothers, 10 experienced a total of 14 AEs, and all were consistent with the known safety profile of certolizumab pegol.

In summary, more than one-half of breast milk samples had undetectable levels of certolizumab pegol, and the remaining samples had less than 1% of a therapeutic plasma dose of certolizumab pegol. These findings indicate minimal to no transfer from the plasma into breast milk, suggesting that continued treatment with certolizumab pegol is compatible with breastfeeding in mothers with chronic inflammatory diseases.

Source: Thorp J, Clowse MEB, Förger F, et al. Evaluating transfer of certolizumab pegol into breast milk: results from a prospective, postmarketing, multicenter pharmacokinetic study. Presented at: Society for Maternal-Fetal Medicine 37th Annual Pregnancy Meeting; January 23-28, 2017; Las Vegas, NV. Abstract 692.