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  • Erythropoietin in amyotrophic lateral sclerosis: a multicentre, randomised, double blind, placebo controlled, phase III study

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Neuromuscular
Research paper
Erythropoietin in amyotrophic lateral sclerosis: a multicentre, randomised, double blind, placebo controlled, phase III study
  1. Giuseppe Lauria1,
  2. Eleonora Dalla Bella1,
  3. Giovanni Antonini2,
  4. Giuseppe Borghero3,
  5. Margherita Capasso4,
  6. Claudia Caponnetto5,
  7. Adriano Chiò6,
  8. Massimo Corbo7,8,
  9. Roberto Eleopra9,
  10. Raffaella Fazio10,
  11. Massimiliano Filosto11,
  12. Fabio Giannini12,
  13. Enrico Granieri13,
  14. Vincenzo La Bella14,
  15. Giancarlo Logroscino15,
  16. Jessica Mandrioli16,
  17. Letizia Mazzini17,
  18. Maria Rosaria Monsurrò18,
  19. Gabriele Mora19,
  20. Vladimiro Pietrini20,
  21. Rocco Quatrale21,
  22. Romana Rizzi22,
  23. Fabrizio Salvi23,
  24. Gabriele Siciliano24,
  25. Gianni Sorarù25,
  26. Paolo Volanti26,
  27. Irene Tramacere27,
  28. Graziella Filippini27
  29. on behalf of the EPOS Trial Study Group
    1. 1Neuromuscular Disease, IRCCS Foundation, “Carlo Besta” Neurological Institute, Milan, Italy
    2. 2NESMOS Department, Neuromuscular Disease Unit, Sant'Andrea Hospital and University of Rome “Sapienza”, Rome, Italy
    3. 3Neurologic Unit, Monserrato University Hospital, Cagliari, Italy
    4. 4Neurologic Clinic, SS. Annunziata Hospital, Chieti, Italy
    5. 5Departments of Neurosciences, Rehabilitation, Ophtalmology, Genetics, Mother and Child Disease, IRCCS University Hospital San Martino IST, Genova, Italy
    6. 6Department of Neurosciences, ALS Centre, “Rita Levi Montalcini” Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Turin, Italy
    7. 7NEMO Clinical Centre, Milan, Italy
    8. 8Department of Neurorehabilitaton, Casa Cura Policlinico, Milan, Italy
    9. 9Neurology Unit, S. Maria della Misericordia University Hospital, Udine, Italy
    10. 10Department of Neurology, IRCCS “San Raffaele” Hospital, Milan, Italy
    11. 11Neurologic Clinic, University of Brescia, Brescia, Italy
    12. 12Department of Medical and Surgery Sciences and Neurosciences, University of Siena, Siena, Italy
    13. 13Neurologic Clinic, University of Ferrara, Italy
    14. 14ALS Research Centre, BioNeC, University of Palermo, Palermo, Italy
    15. 15Department of Neurology and Psychiatry, University of Bari, Bari, Italy
    16. 16Department of Neurosciences, S. Agostino-Estense Hospital, Modena, Italy
    17. 17ALS Centre, Neurologic Clinic, Maggiore della Carità University Hospital, Novara, Italy
    18. 182nd Neurologic Clinic, 2nd University of Naples, Naples, Italy
    19. 19IRCCS “Salvatore Maugeri” Foundation, Milan, Italy
    20. 20Department of Neurosciences, Neurology Unit, University of Parma, Parma, Italy
    21. 21Neurology Unit, dell'Angelo Hospital, Mestre, Italy
    22. 22Neurology Unit, Department of Neuro-Motor Diseases, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, Italy
    23. 23IRCCS Neurological Sciences Institute, Bologna, Italy
    24. 24Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy
    25. 25Department of Neurosciences, University of Padua, Padua, Italy
    26. 26Intensive Neurorehabilitation Unit, IRCCS “Salvatore Maugeri” Foundation, Mistretta, Italy
    27. 27Neuroepidemiology Units, IRCCS Foundation, “Carlo Besta” Neurological Institute, Milan, Italy
    1. Correspondence to Dr Giuseppe Lauria, 3rd Neurology Unit, Department of Clinical Neurosciences, IRCCS Foundation, “Carlo Besta” Neurological Institute, Via Celoria, 11-20133 Milan, Italy; glauria{at}istituto-besta.it

    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.

    • ALS
    • MOTOR NEURON DISEASE

    This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

    https://doi.org/10.1136/jnnp-2014-308996

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