title: Erythropoietin in amyotrophic lateral sclerosis: a multicentre, randomised, double blind, placebo controlled, phase III study.
abstract: OBJECTIVE
  To assess the efficacy of recombinant human erythropoietin (rhEPO) in amyotrophic lateral sclerosis (ALS).
  
  
  METHODS
  Patients with probable laboratory-supported, probable or definite ALS were enrolled by 25 Italian centres and randomly assigned (1:1) to receive intravenous rhEPO 40,000 IU or placebo fortnightly as add-on treatment to riluzole 100 mg daily for 12 months. The primary composite outcome was survival, tracheotomy or >23 h non-invasive ventilation (NIV). Secondary outcomes were ALSFRS-R, slow vital capacity (sVC) and quality of life (ALSAQ-40) decline. Tolerability was evaluated analysing adverse events (AEs) causing withdrawal. The randomisation sequence was computer-generated by blocks, stratified by centre, disease severity (ALSFRS-R cut-off score of 33) and onset (spinal or bulbar). The main outcome analysis was performed in all randomised patients and by intention-to-treat for the entire population and patients stratified by severity and onset. The study is registered, EudraCT 2009-016066-91.
  
  
  RESULTS
  We randomly assigned 208 patients, of whom 5 (1 rhEPO and 4 placebo) withdrew consent and 3 (placebo) became ineligible (retinal thrombosis, respiratory insufficiency, SOD1 mutation) before receiving treatment; 103 receiving rhEPO and 97 placebo were eligible for analysis. At 12 months, the annualised rate of death (rhEPO 0.11, 95% CI 0.06 to 0.20; placebo: 0.08, CI 0.04 to 0.17), tracheotomy or >23 h NIV (rhEPO 0.16, CI 0.10 to 0.27; placebo 0.18, CI 0.11 to 0.30) did not differ between groups, also after stratification by onset and ALSFRS-R at baseline. Withdrawal due to AE was 16.5% in rhEPO and 8.3% in placebo. No differences were found for secondary outcomes.
  
  
  CONCLUSIONS
  RhEPO 40,000 IU fortnightly did not change the course of ALS.
authors.affiliation: Neuromuscular Disease, IRCCS Foundation, "Carlo Besta" Neurological Institute, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lauria
authors.affiliation: Neuromuscular Disease, IRCCS Foundation, "Carlo Besta" Neurological Institute, Milan, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Dalla Bella
authors.affiliation: NESMOS Department, Neuromuscular Disease Unit, Sant'Andrea Hospital and University of Rome "Sapienza", Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Antonini
authors.affiliation: Neurologic Unit, Monserrato University Hospital, Cagliari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Borghero
authors.affiliation: Neurologic Clinic, SS. Annunziata Hospital, Chieti, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Capasso
authors.affiliation: Departments of Neurosciences, Rehabilitation, Ophtalmology, Genetics, Mother and Child Disease, IRCCS University Hospital San Martino IST, Genova, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Caponnetto
authors.affiliation: Department of Neurosciences, ALS Centre, "Rita Levi Montalcini" Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Turin, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Chiò
authors.affiliation: NEMO Clinical Centre, Milan, Italy Department of Neurorehabilitaton, Casa Cura Policlinico, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Corbo
authors.affiliation: Neurology Unit, S. Maria della Misericordia University Hospital, Udine, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Eleopra
authors.affiliation: Department of Neurology, IRCCS "San Raffaele" Hospital, Milan, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Fazio
authors.affiliation: Neurologic Clinic, University of Brescia, Brescia, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Filosto
authors.affiliation: Department of Medical and Surgery Sciences and Neurosciences, University of Siena, Siena, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Giannini
authors.affiliation: Neurologic Clinic, University of Ferrara, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Granieri
authors.affiliation: ALS Research Centre, BioNeC, University of Palermo, Palermo, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: La Bella
authors.affiliation: Department of Neurology and Psychiatry, University of Bari, Bari, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Logroscino
authors.affiliation: Department of Neurosciences, S. Agostino-Estense Hospital, Modena, Italy.
authors.forename: Jessica
authors.initials: J
authors.lastname: Mandrioli
authors.affiliation: ALS Centre, Neurologic Clinic, Maggiore della Carità University Hospital, Novara, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Mazzini
authors.affiliation: 2nd Neurologic Clinic, 2nd University of Naples, Naples, Italy.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Monsurrò
authors.affiliation: IRCCS "Salvatore Maugeri" Foundation, Milan, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Mora
authors.affiliation: Department of Neurosciences, Neurology Unit, University of Parma, Parma, Italy.
authors.forename: Vladimiro
authors.initials: V
authors.lastname: Pietrini
authors.affiliation: Neurology Unit, dell'Angelo Hospital, Mestre, Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: Quatrale
authors.affiliation: Neurology Unit, Department of Neuro-Motor Diseases, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.
authors.forename: Romana
authors.initials: R
authors.lastname: Rizzi
authors.affiliation: IRCCS Neurological Sciences Institute, Bologna, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Salvi
authors.affiliation: Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siciliano
authors.affiliation: Department of Neurosciences, University of Padua, Padua, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Sorarù
authors.affiliation: Intensive Neurorehabilitation Unit, IRCCS "Salvatore Maugeri" Foundation, Mistretta, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Volanti
authors.affiliation: Neuroepidemiology Units, IRCCS Foundation, "Carlo Besta" Neurological Institute, Milan, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Tramacere
authors.affiliation: Neuroepidemiology Units, IRCCS Foundation, "Carlo Besta" Neurological Institute, Milan, Italy.
authors.forename: Graziella
authors.initials: G
authors.lastname: Filippini
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000401:mortality; D004311:Double-Blind Method; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa
keywords: ALS; MOTOR NEURON DISEASE