There is limited evidence regarding the safety of treatment with biologics in women with chronic inflammatory diseases (eg, rheumatoid arthritis, psoriatic arthritis, and Crohn’s disease) who are breastfeeding. However, results from a recent prospective, multicenter, pharmacokinetic clinical trial support the use of certolizumab pegol therapy in mothers who are breastfeeding, and demonstrated that absorption of certolizumab pegol by infants via breast milk is not likely (Clowse ME, et al. Ann Rheum Dis. 2017 Aug 16. Epub ahead of print).
In the CRADLE study, Megan E.B. Clowse, MD, Associate Professor of Medicine, Duke University School of Medicine, Durham, NC, and colleagues, evaluated the concentrations of certolizumab pegol in mature breast milk of patients receiving this biologic, and calculated the average daily dose of certolizumab pegol potentially ingested by infants being breastfed. In addition, they evaluated the concentration of polyethylene glycol levels in the breast milk, and assessed safety events in mothers and infants.
“While prior studies entailed case reports with few milk samples obtained at varying times after dosing, CRADLE was designed to fully characterize the CZP PK [certolizumab pegol pharmacokinetics] profile in mature milk at steady-state,” Dr. Clowse and colleagues stated.
Between September 8, 2014, and October 30, 2015, they evaluated 17 lactating women who were being treated with certolizumab pegol for an approved indication. Eligible participants had to be ≥6 weeks postpartum, and neither pregnant nor planning to become pregnant during the course of the study.
Mothers in the CRADLE study were given certolizumab pegol in doses of 200 mg every 2 weeks (N = 16) or 400 mg every 4 weeks (N = 1). After receiving ≥3 doses of certolizumab pegol, which is when the investigators considered plasma concentrations of the drug to be at steady-state, the participants had mature breast milk samples collected. Samples were collected on days 0, 2, 4, 6, 8, 10, 12, and 14; the mother treated with certolizumab pegol 400 mg every 4 weeks had an additional sample collected on day 28.
Using optimal analytical methods, Dr. Clowse and colleagues determined the levels of certolizumab pegol and polyethylene glycol in the breast milk. In addition, subgroup analyses were performed based on indications that were present in ≥3 patients (ie, rheumatoid arthritis, Crohn’s disease, and psoriatic arthritis) to determine whether indication had any effect on the transfer of certolizumab pegol into breast milk.
Of the 137 breast milk samples collected, 77 (56%) contained no measurable amount of certolizumab pegol. For 4 of the 17 mothers, all samples collected were below the lower limit of quantification. The estimated average infant dose of certolizumab pegol was 0 to 0.0104 mg/kg daily, and polyethylene glycol was undetectable in 134 of 137 samples.
Results from the subgroup analyses suggested that the transfer of certolizumab pegol into breast milk is not associated with the mother’s indication. Dr Clowse and colleagues also noted that they did not identify any new safety issues related to the use of certolizumab pegol. Adverse events in mothers reflected the current safety profile of the biologic, and adverse events in infants were consistent with those of similarly aged infants not exposed to the drug.
“These findings suggest that the level of CZP [certolizumab pegol] ingested by the suckling infant is minimal and indicate that continuation of CZP treatment is compatible with breast feeding. The robust clinical evidence from the CRADLE study allows breastfeeding women with chronic inflammatory diseases and their treating physicians to make informed decisions regarding their postpartum treatment,” Dr Clowse and colleagues concluded.
“These findings are reassuring and support continuation of CZP [certolizumab pegol] treatment during breast feeding,” they said.