The European Medicines Agency (EMA) has approved the label change for UCB’s CIMZIA® (certolizumab pegol), making it the first anti-TNF for potential use in women with ankylosing spondylitis during both pregnancy and breastfeeding.
Data submitted to regulatory authorities included first-of-their-kind clinical studies demonstrating minimal transfer of CIMZIA® through the placenta and breast milk from mother to infant.
About the CRIB Study1
CRIB was a pharmacokinetic study assessing the potential level of placental transfer of certolizumab pegol from pregnant women to their infants. The study followed 16 women (≥ 30 weeks gestation) who were already receiving certolizumab pegol for approved indications.
The study found that certolizumab pegol levels were below the lower limit of quantification in 13 out of 14 infant blood samples at birth, and in all samples at weeks four and eight. One infant had a minimal CZP level of 0.042µg/mL (infant/mother ratio of 0.09%). No anti-CZP antibodies were detected in mothers, umbilical cords, or infants. These data indicate no to minimal placental transfer of CZP from mothers to infants, suggesting lack of in utero fetal exposure during the third trimester.
In CRIB, adverse events experienced by the infants did not show any patterns or clusters of events suggesting a specific safety signal in children. Safety data in the mothers were in line with the known safety profile of CZP and pregnancy profile of these underlying diseases.
About the CRADLE Study2
The primary objectives of the CRADLE pharmacokinetic study were to determine the concentration of certolizumab pegol in human breast milk and the average daily infant dose, an estimation of the daily dose of maternal certolizumab pegol ingested by the infant over the dosing interval.
Among 137 breast milk samples from 17 mothers, all samples had certolizumab pegol concentrations that were minimal, less than 3 times the lower limit of quantification and less than 1% of the expected therapeutic dose. A post-hoc analysis of the relative infant dose (RID) of certolizumab pegol in breast milk was calculated and ranged from 0.04% to 0.30%. The RID is a useful parameter for assessing drug safety in breastfeeding 2 and experts consider a RID that is less than 10% to be unlikely of concern to infant wellbeing.
In CRADLE, adverse events in the infants of mothers exposed to certolizumab pegol were consistent with those occurring in unexposed infants of similar age. Adverse events in mothers exposed to certolizumab pegol were consistent with the known safety profile of certolizumab pegol.