According to a study published in Annals of the Rheumatic Diseases, minimal to no transfer of certolizumab pegol (CZP) from plasma to breast milk occurs in lactating women receiving the drug to treat various inflammatory diseases.1
The safety of the use of biologics to treat chronic inflammatory disease in women who breastfeed is uncertain. Although the diffusion of monoclonal antibodies into breast milk has been reported,2 existing data do not translate well into evidence-based clinical practice because samples of breast milk have not been collected systematically during specific dosing intervals so that drug-specific assays can be conducted.
However, a new pharmacokinetic study (CRADLE [A Multicenter, Postmarketing Study Evaluating the Concentration of Cimzia® in Mature Breast Milk of Lactating Mothers], ClinicalTrials.gov Identifier: NCT02154425) has spearheaded the effort to analyze concentrations of CZP in samples of human breast milk.2 CRADLE also sought to determine the average daily infant dose (ADID) of maternal CZP.
This study measured samples of breast milk from 17 lactating women who had received ≥3 doses of CZP. The women were receiving CZP at a dosage of either 200 mg every 2 weeks or 400 mg every 4 weeks. Samples were collected from the women on the every-2-week schedule on days 0, 2, 4, 6, 8, 10, 12, and 14. Samples were collected from the women on the every-4 week schedule on the same days, with an additional sample collected on day 28.
High Yield Data Summary
- Fifty-six percent of all breast milk samples had no measurable amounts of CZP. All samples obtained from 4 of 17 mothers were below the LLOQ; the highest CZP concentration found at any point was 0.076 μg/mL.
- The estimated ADID was 0 to 0.0104 mg/kg, median RID was measured at 0.15%, and 134 of 137 samples had undetectable PEG levels. Adverse events in infants from CZP-exposed mothers were comparable with those in unexposed infants of similar age.
Before the CZP dose, milk samples were collected on days 0 and 14 from the women taking 200 mg every 2 weeks and on days 0 and 28 from the women taking 400 mg every 4 weeks.
Optimal analytical methods were used to determine CZP and polyethylene glycol (PEG) levels in the breast milk samples, and the ADID and relative infant dose (RID) were estimated.
The researchers found no measurable amounts of CZP in 77 of 137 breast milk samples (56%). The amounts of CZP in the breast milk samples obtained from 4 of the 17 mothers were below the lower limit of quantification (LLOQ); the highest CZP concentration found in the samples of the remaining 13 mothers who had a measurable concentration at any point was 0.076 μg/mL.
The researchers estimated the ADID to be 0 to 0.0104 mg/kg, the measured median RID was 0.15% (range, 0.04% to 0.30%), and PEG was undetectable in 134 of 137 breast milk samples.
The study also determined that adverse events in the infants of CZP-exposed mothers were comparable with that of unexposed infants of similar age.
Overall, the CZP concentrations with the therapeutic dose were <3 × LLOQ, or <1% of the plasma concentration, indicating limited to no transfer of the drug from plasma to breast milk in lactating women.
Poor absorption of CZP in breast milk could be due to low oral bioavailability of CZP and the Fc-free molecular structure of the drug.
The findings from this study are reassuring, suggesting that the use of CZP to treat chronic inflammatory diseases in postpartum women should be continued during breastfeeding following informed decisions of the women made together with their physicians.
Samples of breast milk were not collected immediately after birth for the following reasons: the limited volume of breast milk available at birth, the difficulty of obtaining samples at the time of birth, and the desire to avoid disrupting initial mother-infant bonding.
- Clowse MEB, Forger F, Hwang C, et al. Minimal to no transfer of certolizumab pegol into breast milk: results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study [published online August 16, 2017]. Ann Rheum Dis.doi:10.1136/annrheumdis-2017-2111384
- Jatsyk GV, Kuvaeva IB, Gribakin SG. Immunological protection of the neonatal gastrointestinal tract: the importance of breast feeding. Acta Paediatr Scand. 1985;74:246-249.