Eculizumab treatment during pregnancy does not affect the complement system activity of the newborn

Abstract

Eculizumab is a humanized IgG2/4 chimeric anti-complement C5 antibody used to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) or atypical hemolytic uremic syndrome. The aim of this study was to evaluate whether or not the complement activity in newborns from pregnant women who receive eculizumab is impaired. A novel eculizumab-C5 complex (E-C5) specific assay was developed and revealed that two newborns carried only 6-7% of the E-C5 detected in their eculizumab-treated PNH mothers. Serum from the pregnant women completely lacked terminal complement pathway activity, whereas the complement activity in the serum of the newborns was completely normal. Data from the pregnant women and their newborns were compared with that of healthy age-matched female controls and healthy newborns, as well as a non-treated pregnant woman with PNH and her newborn. These all showed normal complement activity without detectable E-C5 complexes. Furthermore, absence of eculizumab or E-C5 in the newborn could not be explained by lack of eculizumab binding to the neonatal Fc receptor (FcRn), as eculizumab bound strongly to the receptor in vitro. In conclusion, despite binding to FcRn neither eculizumab nor E-C5 accumulates in fetal plasma, and eculizumab treatment during pregnancy does not impair the complement function in the newborn.

The Complement System and Preeclampsia

“…An increasing number of reports also describe eculizumab treatment for pregnancy-associated aHUS before delivery [78–80]. Eculizumab treatment during pregnancy also does not appear to affect the complement system activity of the newborn [81]. Caution regarding complement blockade during pregnancy is warranted because eculizumab and/or eculizumab-C5 complexes appear to cross the placenta and long-term effects are unknown [82, 81].…”

Sensitive, reliable and easy-performed laboratory monitoring of eculizumab therapy in atypical hemolytic uremic syndrome

“…(28) In several cases serum samples were not available, then the E-C5 complexes were measured in EDTA plasma, as indicated in footnote of Table 2.…”

Eculizumab treatment efficiently prevents C5 cleavage without C5a generation in vivo

“…Interestingly, we found a correlation between the BD C5a assay and the eculizumab-C5 complexes, in an assay described by us recently. 7 These data underscore the importance of confirming unexpected and surprising data by using alternative and different assays, instead Figure 1. Effect of eculizumab on C5a and sC5b-9 generation in vivo and in vitro.…”

“…5,7,8 Cofiell et al suggested that urinary C5a and sC5b-9 levels may be more useful in guiding response to eculizumab, 8 …”