title: Impact of eculizumab treatment on paroxysmal nocturnal hemoglobinuria: a treatment versus no-treatment study.
abstract: Intravascular hemolysis in Paroxysmal nocturnal hemoglobinuria (PNH) can effectively be controlled with eculizumab, a humanized monoclonal antibody that binds complement protein C5. We report here a retrospective comparison study between 123 patients treated with eculizumab in the recent period (>2005) and 191 historical controls (from the French registry). Overall survival (OS) at 6 years was 92% (95%CI, 87 to 98) in the eculizumab cohort versus 80% (95%CI 70 to 91) in historical controls diagnosed after 1985 (HR 0.38 [0.15 to 0.94], P = 0.037). There were significantly fewer thrombotic events (TEs) in the group of patients treated with eculizumab (4% [1-10]) as compared to the historical cohort (27% [20-34]). However, we found that TEs may still occur after the initiation of eculizumab treatment and that previous TEs still have a negative impact on survival. Evolutions to myelodysplastic syndrome or acute leukemia were similar in both cohorts. There was less evolution to aplastic anemia in the treatment group. In multivariate analysis, absence of a previous TE and treatment with eculizumab were associated with a better OS. Treatment with eculizumab improves overall survival in classic PNH patients without increasing the risk of clonal evolution.
authors.affiliation: Hematology-Transplantation Department, AP-HP, Saint-Louis Hospital, Paris, France.|Hematology Department, Centre Henri BECQUEREL, Rouen, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Loschi
authors.affiliation: Center for Clinical Epidemiology, AP-HP, Hotel-Dieu Hospital, Inserm U1153, University Paris Descartes, Paris, France.
authors.forename: Raphael
authors.initials: R
authors.lastname: Porcher
authors.affiliation: Hematology Department, Centre Hospitalier Lyon Sud, Pierre Bénite, France.
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Barraco
authors.affiliation: Hematology Department, Hôpital Claude Huriez, Lille, France.
authors.forename: Louis
authors.initials: L
authors.lastname: Terriou
authors.affiliation: Hematology Department, AP-HP, Saint Antoine Hospital, Paris, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.affiliation: Hematology Department, University Hospital Pontchaillou, Rennes, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: de Guibert
authors.affiliation: Hematology Department, University Hospital, Nantes, France.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Mahe
authors.affiliation: Hematology Department, University Hospital, Clermont Ferrand, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Lemal
authors.affiliation: Hematology Department, Groupe Hospitalier Sud, Pessac, France.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Dumas
authors.affiliation: Hematology Department, Groupe Hospitalier Sud, Pessac, France.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Etienne
authors.affiliation: Hematology Department, Centre Henri BECQUEREL, Rouen, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Jardin
authors.affiliation: Hematology Department, University Hospital Amiens Sud, Amiens, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Royer
authors.affiliation: Hematology Department, University Hospital, Limoges, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bordessoule
authors.affiliation: Hematology Department, University Hospital L'archer, Nice, France.
authors.forename: Pierre Simon
authors.initials: PS
authors.lastname: Rohrlich
authors.affiliation: Hematology Department, University Hospital Hautepierre, Strasbourg, France.
authors.forename: Luc Mathieu
authors.initials: LM
authors.lastname: Fornecker
authors.affiliation: Hematology Department, Hospital Sud Francilien, Corbeil, France.
authors.forename: Celia
authors.initials: C
authors.lastname: Salanoubat
authors.affiliation: Hematology Department, AP-HP, Henri-Mondor Hospital, Créteil, France.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Maury
authors.affiliation: Hematology Department, University Hospital, Grenoble, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Cahn
authors.affiliation: Hematology Department, University Hospital, Montpellier, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Vincent
authors.affiliation: Internal Medicine Department, Foch Hospital, Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Sene
authors.affiliation: Hematology Department, Versailles Hospital, Versailles, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Rigaudeau
authors.affiliation: Hematology Department, AP-HP, Pitié Salpetriere Hospital, Paris, France.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Nguyen
authors.affiliation: Transfusion Department, Etablissement Français Du Sang, Site Saint-Louis, Paris, France.
authors.forename: Anne-Claire
authors.initials: AC
authors.lastname: Lepretre
authors.affiliation: Statistics, AP-HP, Saint-Louis Hospital, Inserm U1153, Paris, France.|Sorbonne Paris Cité, University Paris Diderot, Paris, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Mary
authors.affiliation: Hematology Department, Annecy Hospital, France.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Corront
authors.affiliation: Hematology-Transplantation Department, AP-HP, Saint-Louis Hospital, Paris, France.|Sorbonne Paris Cité, University Paris Diderot, Paris, France.
authors.forename: Gerard
authors.initials: G
authors.lastname: Socie
authors.affiliation: Hematology-Transplantation Department, AP-HP, Saint-Louis Hospital, Paris, France.|Sorbonne Paris Cité, University Paris Diderot, Paris, France.
authors.forename: Regis
authors.initials: R
authors.lastname: Peffault de Latour
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D003182:Complement C5 / Q000037:antagonists & inhibitors; D005260:Female; D005500:Follow-Up Studies; D006457:Hemoglobinuria, Paroxysmal / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003182:Complement C5; C481642:eculizumab