Ravulizumab for treatment of paroxysmal nocturnal hemoglobinuria during pregnancy.

Ravulizumab, a humanized, long-acting monoclonal antibody against complement factor C5, is a widely used treatment for paroxysmal nocturnal hemoglobinuria (PNH). Given that pregnant women with PNH are at increased risk for complications and the safety and efficacy of ravulizumab in pregnancy is not known, we performed an international multicenter retrospective analysis of 16 patients with PNH with 19 pregnancies managed with ravulizumab and compared outcomes to 8 earlier pregnancies in the same patients treated with eculizumab. Of the 8 eculizumab-treated pregnancies, 3 resulted in miscarriages and 1 in early preterm delivery for threatened fetal demise and massive fetal growth retardation. All 19 pregnancies on ravulizumab resulted in the birth of live infants, with a median gestational age of 267 days (interquartile range [IQR], 259-275) and median birth weight of 3115 g (IQR, 2458-3349). Cord blood testing in 2 pregnancies receiving intensified ravulizumab dosing revealed detectable ravulizumab levels consistent with transplacental transfer. After a median follow-up of 16.2 months (IQR, 4.4-40.1), no developmental abnormalities or severe infectious complications were observed in the children. This retrospective analysis provides evidence for the safety and effectiveness of ravulizumab in managing PNH during pregnancy and breastfeeding with favorable maternal and fetal outcomes.