TY - JOUR
T1 - Lack of placental transfer of certolizumab pegol during pregnancy
T2 - Results from CRIB, a prospective, postmarketing, pharmacokinetic study
AU - Mariette, Xavier
AU - Förger, Frauke
AU - Abraham, Bincy
AU - Flynn, Ann D.
AU - Moltó, Anna
AU - Flipo, René Marc
AU - Van Tubergen, Astrid
AU - Shaughnessy, Laura
AU - Simpson, Jeff
AU - Teil, Marie
AU - Helmer, Eric
AU - Wang, Maggie
AU - Chakravarty, Eliza F.
N1 - Funding Information:
1Université paris-Sud, Hôpitaux Universitaires paris-Sud, InSErM, Le Kremlin-Bicêtre, France 2Inselspital, University Hospital and University of Bern, Bern, Switzerland 3Houston Methodist Hospital, Houston, texas, USA 4University of Utah Health, Salt Lake City, Utah, USA 5department of rheumatology, Hôpital Cochin, Assistance publique – Hôpitaux de paris, InSErM, paris, France 6Centre Hospitalier regional Universitaire de Lille, Lille, nord-pas-de-Calais, France 7department of Medicine, division of rheumatology and CApHrI - Care and public Health research Institute Maastricht, Maastricht University Medical Center, Maastricht, netherlands 8UCB pharma, raleigh, north Carolina, USA 9UCB pharma, Slough, UK 10UCB pharma, Brussels, Belgium 11oklahoma Medical research Foundation, oklahoma City, oklahoma, USA Acknowledgements this study was funded by UCB pharma. We are indebted to the mothers and their infants for their altruistic participation in this study. We thank the nurses and the investigator teams, the study coordination team including Samia Elyakhlifi and Lien Heinzen, UCB pharma, and nicole Hurst, ppd. We also acknowledge Amanda Golembesky, UCB pharma, raleigh, nC, USA, and Gerry parker, UCB pharma, Slough, UK, for their contributions; Cécile Ecoffet, pharmd, and Simone E. Auteri, MSc, UCB pharma, Brussels, Belgium, for publication coordination; and ricardo Milho, phd, and Julia Bárdos, phd, from Costello Medical, Cambridge, UK, for medical writing and editorial assistance in preparing this manuscript for publication, based on the authors’ input and direction.
Publisher Copyright:
© 2018 Article author(s).
PY - 2018/2
Y1 - 2018/2
N2 - OBJECTIVES: There is a need for effective and safe treatment during pregnancy in women with chronic inflammatory diseases. This study evaluated placental transfer of certolizumab pegol (CZP), an Fc-free anti-tumour necrosis factor drug, from CZP-treated pregnant women to their infants.METHODS: CRIB was a pharmacokinetic (PK) study of women ≥30 weeks pregnant receiving commercial CZP for a locally approved indication (last dose ≤35 days prior to delivery). Blood samples were collected from mothers, umbilical cords and infants at delivery, and infants again at weeks 4 and 8 post-delivery. CZP plasma concentrations were measured with a highly sensitive and CZP-specific electrochemiluminescence immunoassay (lower limit of quantification 0.032 μg/mL).RESULTS: Sixteen women entered and completed the study. Maternal CZP plasma levels at delivery were within the expected therapeutic range (median [range] 24.4 [5.0-49.4] μg/mL). Of the 16 infants, 2 were excluded from the per-protocol set: 1 due to missing data at birth and 1 due to implausible PK data. Of the remaining 14 infants, 13 had no quantifiable CZP levels at birth (<0.032 μg/mL), and 1 had a minimal CZP level of 0.042 μg/mL (infant/mother plasma ratio 0.0009); no infants had quantifiable CZP levels at weeks 4 and 8. Of 16 umbilical cord samples, 1 was excluded due to missing data; 3/15 had quantifiable CZP levels (maximum 0.048 μg/mL).CONCLUSIONS: There was no to minimal placental transfer of CZP from mothers to infants, suggesting lack of
in utero foetal exposure during the third trimester. These results support continuation of CZP treatment during pregnancy, when considered necessary.
TRIAL REGISTRATION NUMBER: NCT02019602; Results.
AB - OBJECTIVES: There is a need for effective and safe treatment during pregnancy in women with chronic inflammatory diseases. This study evaluated placental transfer of certolizumab pegol (CZP), an Fc-free anti-tumour necrosis factor drug, from CZP-treated pregnant women to their infants.METHODS: CRIB was a pharmacokinetic (PK) study of women ≥30 weeks pregnant receiving commercial CZP for a locally approved indication (last dose ≤35 days prior to delivery). Blood samples were collected from mothers, umbilical cords and infants at delivery, and infants again at weeks 4 and 8 post-delivery. CZP plasma concentrations were measured with a highly sensitive and CZP-specific electrochemiluminescence immunoassay (lower limit of quantification 0.032 μg/mL).RESULTS: Sixteen women entered and completed the study. Maternal CZP plasma levels at delivery were within the expected therapeutic range (median [range] 24.4 [5.0-49.4] μg/mL). Of the 16 infants, 2 were excluded from the per-protocol set: 1 due to missing data at birth and 1 due to implausible PK data. Of the remaining 14 infants, 13 had no quantifiable CZP levels at birth (<0.032 μg/mL), and 1 had a minimal CZP level of 0.042 μg/mL (infant/mother plasma ratio 0.0009); no infants had quantifiable CZP levels at weeks 4 and 8. Of 16 umbilical cord samples, 1 was excluded due to missing data; 3/15 had quantifiable CZP levels (maximum 0.048 μg/mL).CONCLUSIONS: There was no to minimal placental transfer of CZP from mothers to infants, suggesting lack of
in utero foetal exposure during the third trimester. These results support continuation of CZP treatment during pregnancy, when considered necessary.
TRIAL REGISTRATION NUMBER: NCT02019602; Results.
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U2 - 10.1136/annrheumdis-2017-212196
DO - 10.1136/annrheumdis-2017-212196
M3 - Article
C2 - 29030361
AN - SCOPUS:85041492609
SN - 0003-4967
VL - 77
SP - 228
EP - 233
JO - Annals of the Rheumatic Diseases
JF - Annals of the Rheumatic Diseases
IS - 2
ER -