Successful Pregnancy Outcomes in Paroxysmal Nocturnal Hemoglobinuria with Long-Term Eculizumab Treatment

• Published in: Blood 2008-11, Vol.112 (11), p.4576-4576
• Main Authors: Kelly, Richard, Arnold, Louise, Richards, Stephen J., Hill, Anita, Bomken, Charlotte, Hanley, John, Loughney, Andrew, Khursigara, Gus, Rother, Russell P., Chalmers, Elizabeth, Fitzsimons, Edward, Nakamura, Ryotaro, Gaya, Anna, Rotoli, Bruno, Risitano, Antonio M., Schubert, Joerg, Hillmen, Peter
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V112.11.4576.4576

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by a lack of the terminal complement inhibitor CD59 on erythrocytes that renders these cells susceptible to chronic hemolysis resulting in anemia, fatigue, abdominal pain, kidney dysfunction, pulmonary hypertension, and life-threatening thromboembolism (TE). During pregnancy, hemolysis frequently worsens and the incidence of TE increases, posing a high risk of both fetal and maternal mortality. Eculizumab is a terminal complement inhibitor that reduces hemolysis, transfusion requirements, and TE while improving fatigue and quality of life in patients with PNH. Eculizumab contains a hybrid constant region with components of both IgG2 and IgG4. Whether eculizumab crosses the placenta is not known. The eculizumab clinical trial protocols specified withdrawal of patients who became pregnant during the study. There were 5 reported pregnancies during the PNH clinical trials (n=195) prior to withdrawal from the study. To evaluate the safety and efficacy of eculizumab in the management of PNH during pregnancy, we reviewed the physician-reported adverse events (AEs), PK/PD, and distribution of eculizumab, duration of drug exposure during gestation, complications during and after pregnancy, and general health of the newborn in patients with PNH who became pregnant during the eculizumab clinical trials. Of the 5 reported pregnancies, one patient elected termination and 3 patients withdrew from eculizumab therapy between 4 to 16 weeks of gestation and continued pregnancy through term. There were no apparent complications or AEs related to drug and all 3 patients delivered healthy newborns. One patient was treated with low molecular weight heparin (LMWH) from the time she discontinued eculizumab to three months after delivery. She developed hyperpyrexia and was diagnosed with fever of unknown origin shortly after delivery. She was treated and then discharged. There have been no reported postpartum complications in any of these deliveries to date. The fifth patient withdrew from the study but continued on eculizumab treatment throughout the whole pregnancy and post-partum. She initiated eculizumab treatment in 2002 reducing her LDH from 10,300U/L to 490 U/L (normal range 150 to 480 U/L). Her transfusion requirement reduced from 4 units every 6 weeks to 2 units per year in order to maintain her hemoglobin above 8 g/dl. She was commenced on LMWH at week 8 of gestation and she remained on it for the duration of her