Eculizumab in Pregnant Patients with Paroxysmal Nocturnal Hemoglobinuria.
BACKGROUND
Eculizumab, a humanized monoclonal antibody against complement protein C5 that inhibits terminal complement activation, has been shown to prevent complications of paroxysmal nocturnal hemoglobinuria (PNH) and improve quality of life and overall survival, but data on the use of eculizumab in women during pregnancy are scarce.


METHODS
We designed a questionnaire to solicit data on pregnancies in women with PNH and sent it to the members of the International PNH Interest Group and to the physicians participating in the International PNH Registry. We assessed the safety and efficacy of eculizumab in pregnant patients with PNH by examining the birth and developmental records of the children born and adverse events in the mothers.


RESULTS
Of the 94 questionnaires that were sent out, 75 were returned, representing a response rate of 80%. Data on 75 pregnancies in 61 women with PNH were evaluated. There were no maternal deaths and three fetal deaths (4%). Six miscarriages (8%) occurred during the first trimester. Requirements for transfusion of red cells increased during pregnancy, from a mean of 0.14 units per month in the 6 months before pregnancy to 0.92 units per month during pregnancy. Platelet transfusions were given in 16 pregnancies. In 54% of pregnancies that progressed past the first trimester, the dose or the frequency of use of eculizumab had to be increased. Low-molecular-weight heparin was used in 88% of the pregnancies. Ten hemorrhagic events and 2 thrombotic events were documented; both thrombotic events occurred during the postpartum period. A total of 22 births (29%) were premature. Twenty cord-blood samples were examined for the presence of eculizumab; the drug was detected in 7 of the samples. A total of 25 babies were breast-fed, and in 10 of these cases, breast milk was examined for the presence of eculizumab; the drug was not detected in any of the 10 breast-milk samples.


CONCLUSIONS
Eculizumab provided benefit for women with PNH during pregnancy, as evidenced by a high rate of fetal survival and a low rate of maternal complications. (ClinicalTrials.gov number, NCT01374360.).
From Department of Haematology, St. James's University Hospital, Leeds (R.J.K., A.H.), and Haematological Medicine, Kings College Hospital, London (A.K.) - both in the United Kingdom; University of Ulm and German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen, Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, Ulm (B.H., H.S.), and Department of Hematology, University Hospital of Essen, Essen (A.R.) - both in Germany; PNH Subcommittee of the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation, Leiden (B.H., A.K., A.M.R., L.T., H.S., R.P.L.), and Radboud University Medical Center, Nijmegen (P.M.) - both in the Netherlands; Department of Clinical Haematology, the Royal Melbourne Hospital and University of Melbourne, Parkville, VIC, Australia (J.S.); Department of Hematology, University Hospital, Rennes (S.G.), Clinical Immunology, Department of Internal Medicine, University Hospital of Lille, Lille (L.T.), and Assistance Publique-Hôpitaux de Paris, Service d'Hématologie-Greffe, Hôpital Saint-Louis, University Paris Diderot, Sorbonne Paris Cité, Centre de Référence Aplasie Médullaire-HPN, and Filière de Santé Maladie Rare Immuno-Hématologique (MARIH), Paris (R.P.L.) - all in France; Jane Anne Nohl Division of Hematology, Keck School of Medicine of University of Southern California, Los Angeles (I.C.W.); Department of Hematology, Helsinki University Central Hospital, Helsinki (E.A.); Hematology, Department of Clinical Medicine and Surgery, Federico II, University of Naples, Naples, Italy (A.M.R.); Hematology and Thromboembolism, McMaster University, Hamilton, ON, Canada (C.J.P.); and ICON Clinical Research, San Francisco (M.P.T.).
Richard J
RJ
Kelly
Britta
B
Höchsmann
Jeff
J
Szer
Austin
A
Kulasekararaj
Sophie
S
de Guibert
Alexander
A
Röth
Ilene C
IC
Weitz
Elina
E
Armstrong
Antonio M
AM
Risitano
Christopher J
CJ
Patriquin
Louis
L
Terriou
Petra
P
Muus
Anita
A
Hill
Michelle P
MP
Turner
Hubert
H
Schrezenmeier
Regis
R
Peffault de Latour
D000293:Adolescent; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D003182:Complement C5 / Q000037:antagonists & inhibitors*; D005260:Female; D005313:Fetal Death; D006457:Hemoglobinuria, Paroxysmal / Q000188:drug therapy*; D006801:Humans; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000188:drug therapy*; D047928:Premature Birth / Q000453:epidemiology; D012042:Registries; D011795:Surveys and Questionnaires; D055815:Young Adult
D061067:Antibodies, Monoclonal, Humanized; D003182:Complement C5; C481642:eculizumab