Minimal to no transfer of certolizumab pegol into breast milk: results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study

Megan E. B. Clowse; Frauke Forger; Caroline Hwang; John Thorp; Radboud J. E. M. Dolhain; Astrid van Tubergen; Laura Shaughnessy; Jeff Simpson; Marie Teil; Nathalie Toublanc; Maggie Wang; Thomas W. Hale

doi:10.1136/annrheumdis-2017-211384

Minimal to no transfer of certolizumab pegol into breast milk: results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study

Megan E. B. Clowse^*, Frauke Forger, Caroline Hwang, John Thorp, Radboud J. E. M. Dolhain, Astrid van Tubergen, Laura Shaughnessy, Jeff Simpson, Marie Teil, Nathalie Toublanc, Maggie Wang, Thomas W. Hale

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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

Original language	English
Pages (from-to)	1890-1896
Number of pages	7
Journal	Annals of the Rheumatic Diseases
Volume	76
Issue number	11
DOIs	https://doi.org/10.1136/annrheumdis-2017-211384
Publication status	Published - Nov 2017

Keywords

INFLAMMATORY-BOWEL-DISEASE
RHEUMATOID-ARTHRITIS
CROHNS-DISEASE
DOUBLE-BLIND
PREGNANCY
ETANERCEPT
INFLIXIMAB
MANAGEMENT
MOTHER
TRACT

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Cite this

Clowse, M. E. B., Forger, F., Hwang, C., Thorp, J., Dolhain, R. J. E. M., van Tubergen, A., Shaughnessy, L., Simpson, J., Teil, M., Toublanc, N., Wang, M., & Hale, T. W. (2017). Minimal to no transfer of certolizumab pegol into breast milk: results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study. Annals of the Rheumatic Diseases, 76(11), 1890-1896. https://doi.org/10.1136/annrheumdis-2017-211384

@article{578c487380b44025a5851ff8c43de487,

title = "Minimal to no transfer of certolizumab pegol into breast milk: results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study",

abstract = "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",

keywords = "INFLAMMATORY-BOWEL-DISEASE, RHEUMATOID-ARTHRITIS, CROHNS-DISEASE, DOUBLE-BLIND, PREGNANCY, ETANERCEPT, INFLIXIMAB, MANAGEMENT, MOTHER, TRACT",

author = "Clowse, {Megan E. B.} and Frauke Forger and Caroline Hwang and John Thorp and Dolhain, {Radboud J. E. M.} and {van Tubergen}, Astrid and Laura Shaughnessy and Jeff Simpson and Marie Teil and Nathalie Toublanc and Maggie Wang and Hale, {Thomas W.}",

year = "2017",

month = nov,

doi = "10.1136/annrheumdis-2017-211384",

language = "English",

volume = "76",

pages = "1890--1896",

journal = "Annals of the Rheumatic Diseases",

issn = "0003-4967",

publisher = "BMJ Publishing Group",

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}

Clowse, MEB, Forger, F, Hwang, C, Thorp, J, Dolhain, RJEM, van Tubergen, A, Shaughnessy, L, Simpson, J, Teil, M, Toublanc, N, Wang, M & Hale, TW 2017, 'Minimal to no transfer of certolizumab pegol into breast milk: results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study', Annals of the Rheumatic Diseases, vol. 76, no. 11, pp. 1890-1896. https://doi.org/10.1136/annrheumdis-2017-211384

Minimal to no transfer of certolizumab pegol into breast milk: results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study. / Clowse, Megan E. B.; Forger, Frauke; Hwang, Caroline et al.
In: Annals of the Rheumatic Diseases, Vol. 76, No. 11, 11.2017, p. 1890-1896.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Minimal to no transfer of certolizumab pegol into breast milk

T2 - results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study

AU - Clowse, Megan E. B.

AU - Forger, Frauke

AU - Hwang, Caroline

AU - Thorp, John

AU - Dolhain, Radboud J. E. M.

AU - van Tubergen, Astrid

AU - Shaughnessy, Laura

AU - Simpson, Jeff

AU - Teil, Marie

AU - Toublanc, Nathalie

AU - Wang, Maggie

AU - Hale, Thomas W.

PY - 2017/11

Y1 - 2017/11

N2 - 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

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

KW - INFLAMMATORY-BOWEL-DISEASE

KW - RHEUMATOID-ARTHRITIS

KW - CROHNS-DISEASE

KW - DOUBLE-BLIND

KW - PREGNANCY

KW - ETANERCEPT

KW - INFLIXIMAB

KW - MANAGEMENT

KW - MOTHER

KW - TRACT

U2 - 10.1136/annrheumdis-2017-211384

DO - 10.1136/annrheumdis-2017-211384

M3 - Article

C2 - 28814432

SN - 0003-4967

VL - 76

SP - 1890

EP - 1896

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

IS - 11

ER -