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J Neurol Neurosurg Psychiatry. 2015 Aug;86(8):879-86. doi: 10.1136/jnnp-2014-308996. Epub 2015 Jan 16.

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

Author information

1
Neuromuscular Disease, IRCCS Foundation, "Carlo Besta" Neurological Institute, Milan, Italy.
2
NESMOS Department, Neuromuscular Disease Unit, Sant'Andrea Hospital and University of Rome "Sapienza", Rome, Italy.
3
Neurologic Unit, Monserrato University Hospital, Cagliari, Italy.
4
Neurologic Clinic, SS. Annunziata Hospital, Chieti, Italy.
5
Departments of Neurosciences, Rehabilitation, Ophtalmology, Genetics, Mother and Child Disease, IRCCS University Hospital San Martino IST, Genova, Italy.
6
Department of Neurosciences, ALS Centre, "Rita Levi Montalcini" Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Turin, Italy.
7
NEMO Clinical Centre, Milan, Italy Department of Neurorehabilitaton, Casa Cura Policlinico, Milan, Italy.
8
Neurology Unit, S. Maria della Misericordia University Hospital, Udine, Italy.
9
Department of Neurology, IRCCS "San Raffaele" Hospital, Milan, Italy.
10
Neurologic Clinic, University of Brescia, Brescia, Italy.
11
Department of Medical and Surgery Sciences and Neurosciences, University of Siena, Siena, Italy.
12
Neurologic Clinic, University of Ferrara, Italy.
13
ALS Research Centre, BioNeC, University of Palermo, Palermo, Italy.
14
Department of Neurology and Psychiatry, University of Bari, Bari, Italy.
15
Department of Neurosciences, S. Agostino-Estense Hospital, Modena, Italy.
16
ALS Centre, Neurologic Clinic, Maggiore della Carità University Hospital, Novara, Italy.
17
2nd Neurologic Clinic, 2nd University of Naples, Naples, Italy.
18
IRCCS "Salvatore Maugeri" Foundation, Milan, Italy.
19
Department of Neurosciences, Neurology Unit, University of Parma, Parma, Italy.
20
Neurology Unit, dell'Angelo Hospital, Mestre, Italy.
21
Neurology Unit, Department of Neuro-Motor Diseases, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.
22
IRCCS Neurological Sciences Institute, Bologna, Italy.
23
Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy.
24
Department of Neurosciences, University of Padua, Padua, Italy.
25
Intensive Neurorehabilitation Unit, IRCCS "Salvatore Maugeri" Foundation, Mistretta, Italy.
26
Neuroepidemiology Units, IRCCS Foundation, "Carlo Besta" Neurological Institute, Milan, Italy.

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.

KEYWORDS:

ALS; MOTOR NEURON DISEASE

PMID:
25595151
PMCID:
PMC4515982
DOI:
10.1136/jnnp-2014-308996
[Indexed for MEDLINE]
Free PMC Article

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