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

Xavier Mariette, Frauke Förger, Bincy Abraham, Ann D Flynn, Anna Moltó, René-Marc Flipo, Astrid van Tubergen, Laura Shaughnessy, Jeff Simpson, Marie Teil, Eric Helmer, Maggie Wang, Eliza F Chakravarty, Xavier Mariette, Frauke Förger, Bincy Abraham, Ann D Flynn, Anna Moltó, René-Marc Flipo, Astrid van Tubergen, Laura Shaughnessy, Jeff Simpson, Marie Teil, Eric Helmer, Maggie Wang, Eliza F Chakravarty

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.

Keywords: anti-tnf; psoriatic arthritis; rheumatoid arthritis; spondyloarthritis; treatment.

Conflict of interest statement

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.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1
Figure 1
CRIB study design. aLast certolizumab pegol (CZP) dose given within 35 days prior to delivery.
Figure 2
Figure 2
Plasma CZP concentrations in mothers and infants (n=14 mother–infant pairsa). aTwo of 16 infants were excluded from the final per-protocol set: one due to missing data at birth and one due to implausible PK data (ie, data not consistent with a paediatric CZP PK model, based on the expected range of clearance, volume of distribution and subsequent elimination half-life; see online supplementary appendix); bInfant samples were collected within 24 hours post-delivery, while mother samples could be collected within 24 hours before or after delivery; c±7 days (two samples missing); d±7 days. BLQ, below the LLOQ (<0.032 μg/mL); CZP, certolizumab pegol; LLOQ, lower limit of quantification.

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