PT - JOURNAL ARTICLE AU - Megan EB Clowse AU - Frauke Förger AU - Caroline Hwang AU - John Thorp AU - Radboud JEM Dolhain AU - Astrid van Tubergen AU - Laura Shaughnessy AU - Jeff Simpson AU - Marie Teil AU - Nathalie Toublanc AU - Maggie Wang AU - Thomas W Hale TI - Minimal to no transfer of certolizumab pegol into breast milk: results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study AID - 10.1136/annrheumdis-2017-211384 DP - 2017 Nov 01 TA - Annals of the Rheumatic Diseases PG - 1890--1896 VI - 76 IP - 11 4099 - http://ard.bmj.com/content/76/11/1890.short 4100 - http://ard.bmj.com/content/76/11/1890.full SO - Ann Rheum Dis2017 Nov 01; 76 AB - Background 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.Methods 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.Results 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.Conclusion When quantifiable, CZP concentrations were <3× LLOQ (<1% plasma concentration observed with therapeutic dose), indicating 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. 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.Trial registration number NCT02154425; Results.