Placental disposition of eculizumab, C5 and C5-eculizumab in two pregnancies of a woman with paroxysmal nocturnal haemoglobinuria

Eculizumab is known to cross the placenta to a limited degree, but recently therapeutic drug levels in cord blood were found in a single case. We report maternal, cord and placental levels of unbound eculizumab, C5 and C5-eculizumab in two pregnancies of a paroxysmal nocturnal haemoglobinuria patient who received 900 mg eculizumab every 2 weeks. In both pregnancies, cord blood concentrations of unbound eculizumab were below 4 mu g/mL, while C5-eculizumab levels were 22 and 26 mu g/mL, suggesting that a considerable fraction of C5 was blocked in the newborn. Concentrations in each placenta of unbound eculizumab were 41 +/- 3 and 45 +/- 4 mu g/g tissue, of C5-eculizumab 19 +/- 2 and 32 +/- 3 mu g/g, and of C5 20 +/- 3 and 30 +/- 2 mu g/g (mean +/- SD, in three tissue samples per placenta). Placental levels of unbound eculizumab were higher than those of C5-eculizumab complexes, while maternal concentrations were approximately equal, suggesting selective transport of unbound eculizumab across the placenta.

Automated summary

Eculizumab has been found to cross the placenta to some extent, with therapeutic drug levels observed in cord blood in a single case. In two pregnancies of a paroxysmal nocturnal haemoglobinuria patient receiving 900 mg eculizumab every 2 weeks, maternal, cord, and placental levels of unbound eculizumab, C5, and C5-eculizumab were measured. The levels of unbound eculizumab were higher than C5-eculizumab complexes in the placenta, suggesting selective transport of unbound eculizumab across the placenta.