Placental transfer of certolizumab pegol (CZP) from mothers to infants during pregnancy may be negligible, and therefore, continued use of this anti-TNF treatment for rheumatoid arthritis (RA) through pregnancy may be safe, according to research presented at the Annual European Congress of Rheumatology (EULAR 2017).
“For rheumatologists, the management of RA patients wishing to become pregnant involves balancing the need to withdraw certain drugs, while at the same time keeping disease activity under control. Anti-TNFs are an effective treatment option in RA and spondyloarthritis but, because most cross the placenta, they are often stopped during pregnancy,” said lead author Professor Xavier Mariette, University Hospitals of Paris-Sud, France.
Dr. Mariette and colleagues conducted the CRIB study, enrolling 16 pregnant women with RA who were at 30 weeks or greater gestation receiving maintenance doses of CZP. The last dose came within 35 days of delivery. At delivery, they obtained serum samples from mothers, umbilical cords, and infants, and then again at 4- and 8-weeks post-delivery.
Using a sensitive, CZP-specific electrochemiluminescence immunoassay, with a lower limit of quantification (LLOQ) of 0.032 µg/mL that is 10-times more sensitive than the assay used in previous CZP pharmacokinetic studies, they measured CZP concentrations in mothers, umbilical cords, and infants at birth.
Maternal CZP plasma levels at delivery were below 0.032 µg/mL, and within the expected therapeutic range (median: 24.4 µg/mL), and in 13 of 14 infant blood samples. One infant had a minimal CZP level of 0.042 µg/mL at birth (infant/mother plasma ratio: 0.09%). No infant had quantifiable levels of CZP at week 4 or week 8.
In the umbilical cord samples taken at birth, only 3 of 15 samples had quantifiable CZP levels (maximum: 0.048 µg/mL).
Researchers detected no anti-CZP antibodies in mothers, umbilical cords, or infants. They concluded that the infants of CZP-exposed mothers had a safety profile similar to that of unexposed infants of a similar age.
“The results of this study support the continuation of CZP treatment during pregnancy when considered necessary to control disease activity. We therefore believe that these data will have a significant impact on clinical practice by providing robust information for women who need treatment to keep their disease under control during pregnancy. “However, there will, of course, still be the risk of the typical adverse effects associated with an anti-TNF treatment, such as infection or an immune reaction, which could affect the outcome of the pregnancy,” he cautioned.