Evaluating Placental Transfer of Certolizumab Pegol and Polyethylene Glycol During Pregnancy: Results From CRIB, a Prospective, Post-Marketing, Multicenter, Pharmacokinetic Study

Abstract

Introduction: Women are often affected by chronic inflammatory diseases, such as Crohn's disease, during their child-bearing years. Adequate disease control during this time is crucial to reduce the risk of adverse pregnancy outcomes. Anti-TNFs are efficacious, but because most cross the placenta they are often stopped during pregnancy. CRIB (NCT02019602) aimed to evaluate placental transfer of certolizumab pegol (CZP; a PEGylated, Fc-free anti-TNF) from mothers to infants. CZP results from this study suggested lack of placental transfer.1 In addition, because CZP is PEGylated, an analysis of the transfer of PEG from mother to infant was also performed. Here, we present the PEG data. Methods: CRIB was a pharmacokinetic (PK) study of pregnant women (≥30 weeks [wks] gestation) receiving commercial CZP for an approved indication. Blood samples were collected from mothers and umbilical cords at delivery using Becton Dickinson tubes, and from infants at birth and Wks 4 and 8 postpartum using Sarstedt monovette syringes. CZP plasma levels were measured with a CZP-specific electrochemiluminescence immunoassay (lower limit of quantification [LLOQ]: 0.032 μg/mL). Total PEG (as intact CZP, deconjugated PEG, or other sources of PEG) was measured by nuclear magnetic resonance spectroscopy (LLOQ: 2.5 μg/mL). Results: 16 CZP-treated pregnant women entered the study (Table 1). Using the CZP-specific assay, 13/14 infants and 12/15 umbilical cords had no quantifiable CZP levels at birth. Median [range] of maternal PEG plasma levels at delivery was 30.0 [10.1-59.9] μg/mL, which was in line with CZP level data (Figure). 14/15 cords had no quantifiable PEG levels; 1 cord had 9.8 μg/mL PEG (corresponding CZP level was below LLOQ). Infant PEG data were uninterpretable, due to contamination of sample collection tubes with exogenous PEG. Maternal AEs were in line with the safety profile of CZP and these underlying diseases; AEs in the infants did not suggest a specific safety signal in children (Table 2).FigureConclusion: PEG levels were below LLOQ in 14/15 umbilical cords, which were in line with recently reported CZP data.1 These data indicate no to minimal placental transfer of CZP as well as PEG from mothers to infants, suggesting lack of in utero fetal exposure during the third trimester. These results support continuation of CZP treatment during pregnancy, when considered necessary to control disease activity.FigureFigure