title: A randomized and double-blind controlled trial evaluating the safety and efficacy of rituximab for warm auto-immune hemolytic anemia in adults (the RAIHA study).
abstract: This Phase 3 multicentre randomized double-blind and placebo-controlled trial aimed to compare the efficacy and safety of rituximab (RTX) to placebo for treating newly diagnosed warm autoimmune hemolytic anemia (wAIHA) in adults receiving prednisone. Adults with a confirmed diagnosis of wAIHA who previously received corticosteroids for less than 6 weeks could be included. At inclusion, all patients received prednisone at a daily dose of 1 mg/kg for 2 weeks, and then tapered according to a pre-defined recommended reduction scheme. Besides prednisone, eligible patients received 2 infusions of RTX or placebo at a fixed dose of 1,000 mg 2-week apart. The primary endpoint was overall response rate (complete response [CR] + partial response [PR]) in an intent-to-treat (ITT) analysis at 1 year. A total of 32 patients (17 females [53%], mean age at inclusion 71 ± 16 years) were enrolled and randomized. In all, 27 patients were followed for at least 1 year and their data were evaluable for response. With an ITT analysis, the overall response rate at 1 year was 75% [95%CI: 47.6-92.7] with 11 CR and 1 PR with RTX versus 31% [11.0-58.7] (5 CR) with placebo (P = 0.032). At 2 years, 10/16 patients with RTX versus 3/16 with placebo still showed CR (P = 0.011). Overall, eight severe infections occurred during follow-up, six with placebo and two with RTX (P = 0.39). At 2 years, six patients with placebo had died, but none with RTX (P = 0.017). Compared to placebo, RTX combined with prednisone may be effective and safe for treating newly-diagnosed wAIHA in adults. Am. J. Hematol. 92:23-27, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Internal Medicine, National Referral Center for Adult'Immune Cytopenias Henri Mondor University Hospital, Assistance Publique Hôpitaux de Paris, Université Paris-Est Créteil, Créteil, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Michel
authors.affiliation: Department of Internal Medecine and Clinical Hematology, Claude-Huriez University Hospital, Université Lille Nord de France, Lille, France.
authors.forename: Louis
authors.initials: L
authors.lastname: Terriou
authors.affiliation: Department of Public Health and Statistics, Henri Mondor University Hospital, Assistance Publique Hôpitaux de Paris, Université Paris-Est Créteil, Créteil, France.
authors.forename: Francoise
authors.initials: F
authors.lastname: Roudot-Thoraval
authors.affiliation: Department of Internal Medicine, Hôtel Dieu University Hospital, Nantes, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hamidou
authors.affiliation: Department of Internal Medicine, La Timone University Hospital, Marseille, France.
authors.forename: Mikael
authors.initials: M
authors.lastname: Ebbo
authors.affiliation: Department of Internal Medicine, D'Estaing University Hospital, Clermont Ferrand, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Le Guenno
authors.affiliation: Department of Clinical Immunology, Saint Louis University Hospital, Paris, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Galicier
authors.affiliation: Department of Internal Medicine and Clinical Immunology, Bocage Central University Hospital, CR INSERM 1098, Dijon, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Audia
authors.affiliation: Deparment of Hematology, University Hospital, Amiens, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Royer
authors.affiliation: Department of Internal Medicine, Jean Verdier University Hospital, Bondy, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Morin
authors.affiliation: Department of Internal Medicine and Clinical Immunology Assistance Publique-Hôpitaux de Paris, Bicêtre University Hospital, Université Paris Sud, Le Kremlin-Bicêtre, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Marie Michot
authors.affiliation: Department of Hematology, Dupuytren University Hospital, Limoges, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Jaccard
authors.affiliation: Department of Hematology, Necker University Hospital, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Frenzel
authors.affiliation: Department of Internal Medicine, National Referral Center for Adult'Immune Cytopenias Henri Mondor University Hospital, Assistance Publique Hôpitaux de Paris, Université Paris-Est Créteil, Créteil, France.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Khellaf
authors.affiliation: Department of Internal Medicine, National Referral Center for Adult'Immune Cytopenias Henri Mondor University Hospital, Assistance Publique Hôpitaux de Paris, Université Paris-Est Créteil, Créteil, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Godeau
mesh_terms: D000368:Aged; D000744:Anemia, Hemolytic, Autoimmune / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D000069283:Rituximab / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D007155:Immunologic Factors; D000069283:Rituximab; D011239:Prednisolone