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Eculizumab appears safe, effective for pregnant women with PNH
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Eculizumab conferred a high rate of fetal survival and a low rate of maternal complications among pregnant women with paroxysmal nocturnal hemoglobinuria, according to the results of an observational study.
“Historically, the management of paroxysmal nocturnal hemoglobinuria [PNH] during pregnancy has been challenging, and pregnancy has been discouraged in patients with PNH,” Richard J. Kelly, MBChB, PhD, of the department of hematology at St. James’s University Hospital in Leeds, England, and colleagues wrote. “Intravascular hemolysis and anemia are frequently more severe during pregnancy, with greater transfusion requirements, than in the nonpregnant state. Morbidity and mortality are higher among pregnant women with PNH than among nonpregnant women with PNH, and the risks continue to be high during the postpartum period.”
Eculizumab (Soliris, Alexion Pharmaceuticals) — a humanized monoclonal antibody against complement protein C5 that inhibits terminal complement activation — has demonstrated efficacy in preventing complications of PNH, a rare, acquired stem-cell disorder that is characterized by chronic hemolysis, bone marrow failure and venous thromboembolism. The agent also has improved quality of life and OS, but little data exists on its safety and efficacy in pregnant women.
Kelly and colleagues designed a questionnaire to gather data on pregnancies in women with PNH. They sent their questionnaire to members of the International PNH Interest Group and to physicians participating in the International PNH Registry.
Further, they assessed the safety and efficacy of eculizumab in pregnant patients with PNH by examining the birth and developmental records of children born, as well as adverse events in their mothers.
The researchers distributed 94 questionnaires, with an 80% response rate (n = 75). The study included data from 75 pregnancies in 61 women (median age at PNH diagnosis, 23 years; median age at pregnancy, 29 years).
The median time from PNH diagnosis to pregnancy was 70 months (range, 0-192). Nine women (15%) received a diagnosis of PNH during pregnancy.
No maternal deaths occurred; however, the researchers observed six spontaneous abortions during the first trimester and three stillbirths.
Requirements for red cell transfusions increased during pregnancy, from a mean of 0.14 units per month in the 6 months preceding pregnancy to 0.92 units per month during pregnancy. Further, 16 pregnancies received platelet transfusions.
In 54% (n = 36) of pregnancies that progressed past the first trimester, the dose or the frequency of eculizumab had to be increased. Further, 88% (n = 66) of pregnancies required low–molecular-weight heparin.
The researchers observed 10 hemorrhagic events, as well as two thrombotic events. Both thrombotic events occurred following delivery.
Twenty-nine percent of births (n = 22) occurred prematurely.
Researchers examined 20 available cord-blood samples for the presence of eculizumab and found evidence of the drug in seven samples.
Twenty-five babies were breast-fed, and breast milk samples were available from 10 mothers. Evidence of the drug was not detected in any available samples.
The researchers acknowledged that a comparison of maternal and fetal mortality among pregnancies included in their study with maternal and fetal outcomes among pregnancies observed prior to the availability of eculizumab would be difficult to conduct and would likely lead to selection bias. Further, they noted that a contemporary randomized trial would be unethical.
“Overall, our findings showed acceptable outcomes when eculizumab treatment was used in the management of PNH in patients during pregnancy,” Kelly and colleagues wrote. “Both hematologists and obstetrical care specialists participated in the delivered care to achieve the outcomes reported.” – by Cameron Kelsall
Disclosure: Kelly reports personal fees from Alexion Pharmaceuticals outside the submitted work. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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