Eculizumab Reduces PNH Symptoms in Women During Pregnancy

Diedtra Henderson

September 21, 2015

Eculizumab, which prevents complications of paroxysmal nocturnal hemoglobinuria (PNH), also can help reduce PNH symptoms during pregnancy, is associated with a higher rate of live births, and leaves little trace in breast milk, according to a small study with industry ties published in the September 10 issue of the New England Journal of Medicine.

"The introduction of eculizumab for the treatment of patients with PNH has improved the management of this illness in that it has reduced the mortality and morbidity associated with PNH and has allowed patients who were previously severely affected to lead a relatively normal life," write Richard J. Kelly, MB, ChB, PhD, from the Department of Haematology, St. James's University Hospital, Leeds, United Kingdom, and colleagues. With the reduction in symptoms for young women with PNH, "it can be anticipated that they may consider starting a family."

Dr Kelly and colleagues distributed 94 questionnaires to targeted groups, including physicians who participate in a global registry for the rare disorder. They received responses with data for 61 women with PNH in nine countries who had experienced 75 pregnancies. Three of the pregnancies involved twins.

Overall, there were 69 live births, of which 22 infants were born premature. In addition, there were six spontaneous abortions during the first trimester and three stillbirths.

The disorder is characterized by premature destruction of red blood cells. Transfusion of red cells increased from a mean of 0.14 units per month in the 6 months preceding pregnancy to 0.92 units per month during pregnancy. Low-molecular-weight heparin was administered in 66 pregnancies. Postpartum, 2 of 75 pregnancies had a thrombotic complication, including deep-vein thrombosis in the leg, and mesenteric thrombosis.

Breast milk was examined in 10 of 25 babies who were breast-fed; eculizumab was not detected. The humanized monoclonal antibody was detected in 7 of 20 cord-blood samples.

"Before the use of eculizumab, mortality among pregnant women with PNH was unacceptably high (8 to 20%). In the current study, no maternal deaths were reported, and only two thrombotic events were reported among the patients who were receiving eculizumab, with both events occurring soon after delivery," Dr Kelly and coauthors write.

Pregnancy has been discouraged for patients with PNH. Because premature birth rates were high in pregnancies reported in the survey, the authors argue for careful monitoring.

Jeff Ecker, MD, who chairs the American College of Obstetricians and Gynecologists’ OB committee and practices high-risk obstetrics at Massachusetts General Hospital, said that with very rare disorders in pregnancy, the only way to get new information is from observational studies, such as the work from Dr Kelly and colleagues. “This information, limited as it is...suggests it is appropriate to talk about continuing those medicines” for PNH during pregnancy, Dr Ecker told Medscape Medical News.

The mean age of surviving infants at the time of the study was 31 months, and Dr Ecker said it was “an important first step in reassurance” that no significant adverse events were seen early on among the children.

Young women balance their experience with uncontrolled PNH, the availability of medicine, and the prospect of pregnancy. “You need to accept some uncertainty...but many women are comfortable accepting that,” he said.

The study authors conclude: "Overall, our findings showed acceptable outcomes when eculizumab treatment was used in the management of PNH in patients during pregnancy. Both hematologists and obstetrical care specialists participated in the delivered care to achieve the outcomes reported."

Fourteen of the study authors disclosed having a financial relationship with Alexion Pharmaceuticals Inc, which markets eculizumab under the brand name Soliris. The financial ties include receiving a national coordinator fee for an international PNH registry study, receiving funding for PNH registry data collection, and receiving institutional grants for PNH-related projects; serving as a paid speaker; receiving support for study and research activities; being a paid advisor; being paid to prepare presentations in company-sponsored symposia; receiving honoraria; accepting an unrestricted educational grant; and receiving travel expenses. In addition to Alexion funding, another coauthor disclosed receiving grants from Alnylam, Novartis, and Ra Pharma. Another coauthor disclosed being an employee of ICON Clinical Research, a contract research organization that conducts research on behalf of Alexion. The remaining author and the commentator have disclosed no relevant financial relationships.

N Engl J Med. 2015;373:1032-1039. Abstract

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