Ravulizumab for Treatment of Paroxysmal Nocturnal Hemoglobinuria During Pregnancy

Ravulizumab, a humanized, long-acting monoclonal antibody against complement factor C5, is a widely utilized treatment for paroxysmal nocturnal hemoglobinuria (PNH). As 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 PNH patients with 19 pregnancies managed with ravulizumab and compared outcomes to 8 earlier pregnancies in the same patients treated with eculizumab. Of the eight eculizumab pregnancies, three resulted in miscarriages and one in early preterm delivery for threatened fetal demise and massive fetal growth retardation. All 19 pregnancies on ravulizumab resulted in birth of live infants with a median gestational age of 267 days (interquartile range (IQR) 259-275) and median birth weight of 3115grams (IQR 2458-3349 grams). Cord blood testing in two 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.