학술논문
Erythropoietin in amyotrophic lateral sclerosis: a multicentre, randomised, double blind, placebo controlled, phase III study
Document Type
Academic Journal
Author
Lauria, Giuseppe; Dalla Bella, Eleonora; Antonini, Giovanni; Borghero, Giuseppe; Capasso, Margherita; Caponnetto, Claudia; Chiò, Adriano; Corbo, Massimo; Eleopra, Roberto; Fazio, Raffaella; Filosto, Massimiliano; Giannini, Fabio; Granieri, Enrico; La Bella, Vincenzo; Logroscino, Giancarlo; Mandrioli, Jessica; Mazzini, Letizia; Monsurrò, Maria Rosaria; Mora, Gabriele; Pietrini, Vladimiro; Quatrale, Rocco; Rizzi, Romana; Salvi, Fabrizio; Siciliano, Gabriele; Sorarù, Gianni; Volanti, Paolo; Tramacere, Irene; Filippini, Graziella; Cazzato, Daniele; Cesnik, Edward; Groppo, Elisabetta; Sette, Elisabetta; Pani, Carla; Costantino, Emanuela; Orlandini, Francesco; Boi, Daniela; Querin, Giorgia; DʼAscenzo, Carla; Sagnelli, Anna; Piccirillo, Giovanni; Aiello, Marina; Chetta, Alfredo; Grassi, Andrea; Lunetta, Christian; Maestri, Eleonora; Padovani, Alessandro; Cotelli, Mariasofia; Todeschini, Alice; Morino, Stefania; Di Pasquale, Antonella; Latino, Pamela; Casali, Stefania; Battistini, Stefania; Pirrelli, Marilena; Cantello, Roberto; Nasuelli, Nicola; Servo, Serena; De Gennaro, Riccardo; Gastaldo, Ernesto; Georgoulopoulou, Eleni; Fini, Nicola; Taiello, Alfonsa C.; Colletti, Tiziana; Calvo, Andrea; Moglia, Cristina; Fuda, Giuseppe; Marinou, Kalliopi; Riva, Nilo; Cerri, Federica; Lopez, Ignazio D.; De Cicco, Domenico; Battaglia, Gianluca; Marcello, Norina; Rinaldi, Manuela; Scialò, Carlo; Mantero, Vittorio; Mascolo, Maria; Carlesi, Cecilia; Caldarazzo Ienco, Elena; Di Muzio, Antonio; Verriello, Lorenzo; DʼAmico, Delia; Simone, Isabella L.; Tortelli, Rosanna; Cortese, Rosa; Bartolomei, Ilaria
Source
Journal of Neurology, Neurosurgery & Psychiatry. Aug 01, 2015 86(8):879-886
Subject
Language
English
ISSN
0022-3050
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.