CRIB Trial Evaluates Safety of Certolizumab Pegol in Pregnancy
UCB announced results from the CRIB trial, a pharmacokinetic study of Cimzia (certolizumab pegol), which demonstrated minimal to no transfer of the tumor necrosis factor inhibitor (anti-TNF) monoclonal antibody from pregnant women to their infants. The report was presented at the 2017 Annual European Congress of Rheumatology (EULAR) in Madrid, Spain.
Cimzia is an Fc-free, PEGylated anti-TNF indicated to treat several chronic inflammatory diseases such as rheumatoid arthritis (RA), Crohn's disease (CD), psoriatic arthritis (PsA), axial spondyloarthritis (axSpA), and ankylosing spondylitis (AS).
According to the lead author of CRIB, Xavier Mariette, MD, PhD, Head of Rheumatology of Bicetre Hospital, Paris-Sud University, “[Research] suggests that most of [anti-TNFs] cross the placenta, so they are usually discontinued during pregnancy.” The discontinuation of chronic inflammatory disease therapy, in addition to disease flares that occur during and after pregnancy, predispose women of child-bearing age to inadequate disease control.
The first-of-its-kind study followed 16 patients at ≥30 weeks gestation who have been on Cimzia therapy for RA (n=11), CD (n=3), PsA (n=1), or axSpA/AS (n=1). Patients were evaluated for safety with Cimzia therapy, defined by the potential level of placental transfer of medication from mother to infant. The study utilized a Cimzia-specific immunoassay to analyze blood samples taken from the mother, the umbilical cord, and samples from the infant at delivery, Week 4 and Week 8 post-delivery. The immunoassay used in CRIB proved to be 10 times more sensitive than previous Cimzia assays used, with a lower level of quantification (LLOQ) of 0.032ug/mL.
Results showed that at birth, 13 of 14 infant blood samples had no measurable levels of Cimzia, and at Weeks 4 and 8 after birth, all samples had no measurable levels. Additionally, no anti-Cimzia antibodies were found to be developed in mothers, infants or umbilical cords. The study results suggest that there is no in utero fetal exposure of Cimzia during the second and third trimesters of pregnancy.
The safety profile of infants exposed to Cimzia showed similar safety profiles to those unexposed, and none indicated specific safety signals in children. Regarding common adverse events, events experienced in the study by mothers were consistent with the established safety profile for Cimzia. Such events include upper respiratory tract infection, rash, and urinary tract infection. In previous studies, serious infections such as tuberculosis and invasive fungal infections and malignancies have been reported.
Cimzia was also evaluated in the pharmacokinetic study, CRADLE, and was shown to exhibit minimal to no transfer in breastfeeding.
Cimzia is available in several forms: as 2 pre-filled glass syringes each containing 200mg (1mL) of Cimzia; as a starter kit with 6 pre-filled glass syringes each containing 200mg (1mL) of Cimzia and 6 alcohol swabs; and as lyophilized powder for reconstitution in a pack.
For more information visit Cimzia.com.