Population PK modeling of certolizumab pegol in pregnant women with chronic inflammatory diseases

CPT Pharmacometrics Syst Pharmacol. 2024 Nov;13(11):1904-1914. doi: 10.1002/psp4.13220. Epub 2024 Sep 1.

Abstract

Certolizumab pegol (CZP; CIMZIA™) is the only Fc-free tumor necrosis factor inhibitor with data from a clinical study demonstrating no to minimal placental transfer. The pharmacokinetics (PK) of certolizumab pegol during pregnancy and postpartum in women with chronic inflammatory diseases were assessed using a population PK model based on data from the CHERISH study (NCT04163016), a longitudinal, prospective, open-label PK phase IB study. Model development was performed in NONMEM using a frequentist prior approach, with prior information based on a population PK model for certolizumab pegol in non-pregnant adult patients (NCT04740814). A one-compartment model with first-order absorption (Ka = 0.236 1/day) and linear elimination (CL/F = 0.416 L/day) from the central compartment (V/F = 7.86 L) best described certolizumab pegol PK in the CHERISH study. The structural model parameters were estimated with good precision (RSE < 25%). Baseline BW was included as a covariate on CL/F and V/F. Pregnancy trimester and time-varying log-transformed anti-drug antibody (ADA) titer were identified as the only significant covariates for CL/F with a comparable influence on CL/F. Individuals with higher ADA titer (75th percentile) during pregnancy exhibited CL/F up to 1.43-fold higher relative to individuals postpartum that showed median levels of ADA titer. However, the confidence interval for the combined effect of pregnancy stage and ADA titer effects on CL/F overlapped with the CL/F range of the typical individual postpartum. In addition, simulations showed a large overlap in certolizumab pegol concentrations between pregnant and non-pregnant adults. The findings of this population PK analysis support the maintenance of established certolizumab pegol dosing regimens throughout pregnancy.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Certolizumab Pegol* / administration & dosage
  • Certolizumab Pegol* / pharmacokinetics
  • Certolizumab Pegol* / therapeutic use
  • Chronic Disease
  • Female
  • Humans
  • Inflammation / drug therapy
  • Longitudinal Studies
  • Models, Biological*
  • Postpartum Period
  • Pregnancy
  • Pregnancy Complications* / drug therapy
  • Prospective Studies
  • Young Adult

Substances

  • Certolizumab Pegol