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  • Lack of placental transfer of certolizumab pegol during pregnancy: results from CRIB, a prospective, postmarketing, pharmacokinetic study

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Clinical and epidemiological research
Extended report
Lack of placental transfer of certolizumab pegol during pregnancy: results from CRIB, a prospective, postmarketing, pharmacokinetic study
  1. Xavier Mariette1,
  2. Frauke Förger2,
  3. Bincy Abraham3,
  4. Ann D Flynn4,
  5. Anna Moltó5,
  6. René-Marc Flipo6,
  7. Astrid van Tubergen7,
  8. Laura Shaughnessy8,
  9. Jeff Simpson8,
  10. Marie Teil9,
  11. Eric Helmer10,
  12. Maggie Wang8,
  13. Eliza F Chakravarty11
  1. 1 Université Paris-Sud, Hôpitaux Universitaires Paris-Sud, INSERM, Le Kremlin-Bicêtre, France
  2. 2 Inselspital, University Hospital and University of Bern, Bern, Switzerland
  3. 3 Houston Methodist Hospital, Houston, Texas, USA
  4. 4 University of Utah Health, Salt Lake City, Utah, USA
  5. 5 Department of Rheumatology, Hôpital Cochin, Assistance Publique – Hôpitaux de Paris, INSERM, Paris, France
  6. 6 Centre Hospitalier Regional Universitaire de Lille, Lille, Nord-Pas-de-Calais, France
  7. 7 Department of Medicine, Division of Rheumatology and CAPHRI - Care and Public Health Research Institute Maastricht, Maastricht University Medical Center, Maastricht, Netherlands
  8. 8 UCB Pharma, Raleigh, North Carolina, USA
  9. 9 UCB Pharma, Slough, UK
  10. 10 UCB Pharma, Brussels, Belgium
  11. 11 Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
  1. Correspondence to Profesor Xavier Mariette, Université Paris-Sud, Hôpitaux Universitaires Paris-Sud, INSERM U1184, 63, rue Gabriel-Péri, 94270 Le Kremlin-Bicêtre, France; xavier.mariette{at}aphp.fr

Abstract

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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This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/annrheumdis-2017-212196

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    Footnotes

    • Handling editor Tore K Kvien

    • Contributors XM, FF, BA, ADF, AM, R-MF, AvT, LS, JS, MT, EH, MW and EC contributed to the conception, design, execution or analysis and interpretation of the data. All authors approved the final version of the manuscript for publication.

    • Funding UCB Pharma sponsored the study and the development of the manuscript and reviewed the text to ensure that from a UCB Pharma perspective, the data presented in the publication are scientifically, technically and medically supportable, that they do not contain any information that has the potential to damage the intellectual property of UCB Pharma and that the publication complies with applicable laws, regulations, guidelines and good industry practice. The authors approved the final version to be published after critically revising the manuscript for important intellectual content.

    • Competing interests XM: grant/research support: Biogen, Pfizer, UCB Pharma; consultant for BMS, GSK, LFB, Pfizer, UCB Pharma. FF: grant/research support: UCB Pharma; speaker’s fees: Mepha, Roche, UCB Pharma. BA: grant/research support: Janssen-Cilag, UCB Pharma; speaker’s fees: AbbVie, American Reagent, Janssen-Cilag, UCB Pharma. AF: grant/research support: UCB Pharma. AM: grant/research support: MSD, AbbVie, Pfizer and UCB Pharma; consultant for: MSD, AbbVie, Pfizer, UCB Pharma. R-MF: grant/research support and consultant for: UCB Pharma. AvT: grant/research support: Pfizer, AbbVie, UCB Pharma, Janssen-Cilag, Celgene, Novartis; speaker’s fees: MSD, Janssen-Cilag, Pfizer; consultant for: AbbVie, Novartis, Janssen-Cilag, Pfizer. LS: employee of UCB Pharma. JS: employee of UCB Pharma. MT: employee of UCB Pharma. EH: employee of UCB Pharma. MW: employee of UCB Pharma. EC: grant/research support: UCB Pharma.

    • Patient consent Detail has been removed from this case description/these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.

    • Ethics approval This study was conducted between January 2014 and November 2016 across 11 sites in France, Netherlands, Switzerland and the USA and was approved by local Institutional Review Boards.

    • Provenance and peer review Not commissioned; externally peer reviewed.