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Abstract

<h3>Background</h3> Women with chronic inflammatory diseases face uncertainty regarding the safety of biologics during breast feeding. CRADLE was the first industry-sponsored study to evaluate certolizumab pegol (CZP) concentrations in human breast milk and estimate average daily infant dose (ADID) of maternal CZP. <h3>Methods</h3> CRADLE (NCT02154425) was a pharmacokinetic study of lactating mothers receiving CZP. After ≥3 CZP doses, 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]). Optimal analytical methods were developed to determine CZP and polyethylene glycol (PEG) levels in breast milk. ADID and relative infant dose (RID) were estimated. Safety events in mothers and infants were assessed. <h3>Results</h3> 19 CZP-treated mothers were screened; 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). Estimated 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. <h3>Conclusion</h3> When quantifiable, CZP concentrations were &lt;3× LLOQ (&lt;1% plasma concentration observed with therapeutic dose), indicating no/minimal CZP transfer from plasma to breast milk. RID was 0.15% of maternal dose; &lt;10% is considered unlikely to be of clinical concern. No PEG transfer was observed. CZP absorption by infants via breast milk is unlikely due to its low oral bioavailability and Fc-­free molecular structure. These findings are reassuring and support continuation of CZP treatment during breast feeding. <h3>Trial registration number</h3> NCT02154425; Results.