Clowse MEB, et al. - For this research, they performed a CRADLE, the first industry-sponsored study to assess certolizumab pegol (CZP) concentrations in human breast milk and estimate average daily infant dose (ADID) of maternal CZP. When quantifiable, CZP concentrations were <3× LLOQ (<1% plasma concentration seen with therapeutic dose), demonstrating no/minimal CZP transfer from plasma to breast milk. RID was 0.15% of maternal dose; <10% is considered unlikely to be of clinical concern. They found no PEG transfer in this study. CZP absorption by infants via breast milk is unlikely because of its low oral bioavailability and Fc- free molecular structure. These outcomes are reassuring and support the continuation of CZP treatment amid breastfeeding.

Methods

• This study CRADLE (NCT02154425) was a pharmacokinetic investigation of lactating mothers receiving CZP.
• In this study, breast milk samples were collected across one dosing period (14 days for 200 mg every 2 weeks [Q2W]; 28 days for 400 mg every 4 weeks [Q4W]) after ≥3 CZP doses.
• To determine CZP and polyethylene glycol (PEG) levels in breast milk, optimal analytical methods were developed.
• They estimated ADID and relative infant dose (RID).
• They evaluated safety events in mothers and infants.

Results

• In this study, they screened 19 CZP-treated mothers.
• 17 entered the sampling period: 16 on 200 mg Q2W, 1 on 400 mg Q4W.
• 77/137 (56%) breast milk samples had no measurable CZP.
• For 4/17 mothers, all samples were below the lower limit of quantification (LLOQ).
• Evaluated ADID was 0-0.0104 mg/kg/day; median RID: 0.15%.
• PEG was undetectable in 134/137 samples (results could not be determined in three samples).
• Infants of CZP-exposed mothers had a safety profile consistent with that of unexposed similar-age infants.