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.
- rheumatoid arthritis
- psoriatic arthritis
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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.
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