title: Assessing complement blockade in patients with paroxysmal nocturnal hemoglobinuria receiving eculizumab.
abstract: Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by intravascular hemolysis, which is effectively controlled with eculizumab, a humanized monoclonal antibody that binds complement protein 5 (C5). The residual functional activity of C5 can be screened using a 50% hemolytic complement (CH50) assay, which is sensitive to the reduction, absence, and/or inactivity of any components of the classical and terminal complement pathway. Little data exist on complement blockade during treatment. From 2010 to 2012, clinical data, hemolysis biomarkers, complement assessment, and free eculizumab circulating levels were systematically measured immediately before every injection given to 22 patients with hemolytic PNH while receiving eculizumab therapy. During the study, 6 patients received ≥1 red blood cell transfusion. Lack of detectable CH50 activity (defined by CH50 ≤ 10% of normal values) was found in 184 samples (51%) and was significantly associated with lower lactate dehydrogenase levels (P = .002). Low levels of circulating free eculizumab (<50 µg/mL) correlated with detectable CH50 activity (CH50 > 10%; P = .004), elevated bilirubin levels (P < .0001), and the need for transfusions (P = .034). This study suggests that both CH50 activity and circulating free eculizumab levels may help physicians to manage PNH patients receiving eculizumab.
authors.affiliation: Service d'Hématologie Greffe, Assistance Publique-Hôpitaux de Paris, Hôpital Saint Louis, Paris, France; Equipe d'accueil 3518, Paris, France;
authors.forename: Régis
authors.initials: R
authors.lastname: Peffault de Latour
authors.affiliation: Laboratoire d'Immunologie, Assistance Publique-Hôpitaux de Paris, Hôpital Georges Pompidou, Paris, France; Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche Scientifiques 1138, Cordelier Research Center, Team: "Complement and Diseases," Paris, France;
authors.forename: Véronique
authors.initials: V
authors.lastname: Fremeaux-Bacchi
authors.affiliation: Centre d'Epidémiologie Hôtel-Dieu, Paris, France; Institut National de la Santé et de la Recherche Médicale U1153, Paris, France;
authors.forename: Raphaël
authors.initials: R
authors.lastname: Porcher
authors.affiliation: Service d'Hématologie Greffe, Assistance Publique-Hôpitaux de Paris, Hôpital Saint Louis, Paris, France;
authors.forename: Aliénor
authors.initials: A
authors.lastname: Xhaard
authors.affiliation: Laboratoire d'Immunologie, Assistance Publique-Hôpitaux de Paris, Hôpital Georges Pompidou, Paris, France; Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche Scientifiques 1138, Cordelier Research Center, Team: "Complement and Diseases," Paris, France;
authors.forename: Jérémie
authors.initials: J
authors.lastname: Rosain
authors.affiliation: Laboratoire d'Immunologie, Assistance Publique-Hôpitaux de Paris, Hôpital Georges Pompidou, Paris, France;
authors.forename: Diana Cadena
authors.initials: DC
authors.lastname: Castaneda
authors.affiliation: Laboratoire d'Immunologie, Assistance Publique-Hôpitaux de Paris, Hôpital Georges Pompidou, Paris, France; Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche Scientifiques 1138, Cordelier Research Center, Team: "Complement and Diseases," Paris, France;
authors.forename: Paula
authors.initials: P
authors.lastname: Vieira-Martins
authors.affiliation: Laboratoire d'Immunologie, Assistance Publique-Hôpitaux de Paris, Hôpital Georges Pompidou, Paris, France;
authors.forename: Stéphane
authors.initials: S
authors.lastname: Roncelin
authors.affiliation: Service d'Hématologie Greffe, Assistance Publique-Hôpitaux de Paris, Hôpital Saint Louis, Paris, France;
authors.forename: Paula
authors.initials: P
authors.lastname: Rodriguez-Otero
authors.affiliation: Service d'Hépatologie, Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon, Clichy, France;
authors.forename: Aurélie
authors.initials: A
authors.lastname: Plessier
authors.affiliation: Service d'Hématologie Greffe, Assistance Publique-Hôpitaux de Paris, Hôpital Saint Louis, Paris, France;
authors.forename: Flore
authors.initials: F
authors.lastname: Sicre de Fontbrune
authors.affiliation: Service d'Hématologie Greffe, Assistance Publique-Hôpitaux de Paris, Hôpital Saint Louis, Paris, France;
authors.forename: Sarah
authors.initials: S
authors.lastname: Abbes
authors.affiliation: Service d'Hématologie Greffe, Assistance Publique-Hôpitaux de Paris, Hôpital Saint Louis, Paris, France;
authors.forename: Marie
authors.initials: M
authors.lastname: Robin
authors.affiliation: Service d'Hématologie Greffe, Assistance Publique-Hôpitaux de Paris, Hôpital Saint Louis, Paris, France; Université Paris Diderot, Paris, France; and Institut National de la Santé et de la Recherche Médicale U1160, Paris, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Socié
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D003167:Complement Activation / Q000187:drug effects; D003182:Complement C5 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016903:Drug Monitoring / Q000379:methods*; D017707:Erythrocyte Transfusion; D005260:Female; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006461:Hemolysis / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007118:Immunoassay; D007155:Immunologic Factors / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007262:Infusions, Intravenous; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008875:Middle Aged
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D003182:Complement C5; D007155:Immunologic Factors; C481642:eculizumab; D007770:L-Lactate Dehydrogenase; D001663:Bilirubin