Eculizumab therapy led to “acceptable” outcomes among pregnant women with paroxysmal nocturnal hemoglobinuria, investigators reported Sept. 9 in the New England Journal of Medicine.

No woman who received eculizumab died while pregnant or within 6 months of delivery; historic mortality rates for these patients are 8%-20%, said Dr. Richard Kelly at St. James’s University Hospital in Leeds, England, and his associates. Treatment with the monoclonal antibody, “has reduced mortality and morbidity associated with PNH and has allowed patients who were previously severely affected to lead a relatively normal life.”

The fetal death rate was 4%, resembling rates of 4%-9% from the era before eculizumab, the researchers said. The rate of premature births also was high (29%) as a result of preeclampsia, suspected intrauterine growth retardation, maternal thrombocytopenia, and slowed fetal movements, they said.

Paroxysmal nocturnal hemoglobinuria is a rare, chronic stem-cell disease in which complement-mediated intravascular hemolysis causes anemia, fatigue, and venous thromboembolism ( Adv Exp Med Biol. 2013;735:155-72. ). Increased complement activation during pregnancy intensifies the risk of severe hemolytic anemia, fetal morbidity, and fetal mortality for women with PNH. Eculizumab blocks terminal complement activation by binding complement protein C5, and has improved PNH symptoms to the extent that treated women are more likely to consider pregnancy than in the past.

Dr. Kelly and his associates surveyed members of the International PNH Interest Group to study pregnancy outcomes among these women ( N Engl J. Med. 2015;373:1032-9 ). A total of 80% of clinicians responded, reporting data for 75 pregnancies among 61 women, the investigators said. All patients had PNH diagnosed by flow cytometry, and 61% had begun eculizumab therapy before conception. Median age at first pregnancy was 29 years, with a range of 18 to 40 years. The patients received weekly 600-mg IV infusions for 4 weeks, followed by 900 mg every 14 days. Clinicians increased the dose or treatment frequency at their own discretion if patients showed signs of breakthrough intravascular hemolysis.

Two women experienced thrombotic events during treatment, both of which happened soon after delivery. One was a lower-limb deep venous thrombosis, but the other occurred after a patient received a plasma infusion for postpartum hemorrhage. “Plasma contains high levels of complement and can overcome the effects of eculizumab and thereby render the patient susceptible to complications of PNH,” noted the investigators. “The use of plasma should thus be avoided if possible.” Ten samples of breast milk were negative for eculizumab, they added.

Dr. Kelly and 14 of 15 coauthors reported financial relationships outside this work with Alexion Pharmaceuticals, the maker of eculizumab. One coauthor also reported grant support outside this work from Alnylam Pharmaceuticals, Novartis, and Ra Pharma.