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

Giuseppe Lauria, Eleonora Dalla Bella, Giovanni Antonini, Giuseppe Borghero, Margherita Capasso, Claudia Caponnetto, Adriano Chiò, Massimo Corbo, Roberto Eleopra, Raffaella Fazio, Massimiliano Filosto, Fabio Giannini, Enrico Granieri, Vincenzo La Bella, Giancarlo Logroscino, Jessica Mandrioli, Letizia Mazzini, Maria Rosaria Monsurrò, Gabriele Mora, Vladimiro PietriniRocco Quatrale, Romana Rizzi, Fabrizio Salvi, Gabriele Siciliano, Gianni Sorarù, Paolo Volanti, Irene Tramacere, Graziella Filippini

Research output: Contribution to journalArticle

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 intentionto-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.

Original languageEnglish
Pages (from-to)879-886
Number of pages8
JournalJournal of Neurology, Neurosurgery and Psychiatry
Volume86
Issue number8
DOIs
Publication statusPublished - 2015

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Amyotrophic Lateral Sclerosis
Erythropoietin
Placebos
Noninvasive Ventilation
Tracheotomy
Riluzole
Vital Capacity
Random Allocation
Placebo
Controlled
Respiratory Insufficiency
Thrombosis
Quality of Life
Mutation
Survival
Mortality
Therapeutics
Population
Onset

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Surgery
  • Arts and Humanities (miscellaneous)

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Erythropoietin in amyotrophic lateral sclerosis : A multicentre, randomised, double blind, placebo controlled, phase III study. / Lauria, Giuseppe; Bella, Eleonora Dalla; Antonini, Giovanni; Borghero, Giuseppe; Capasso, Margherita; Caponnetto, Claudia; Chiò, Adriano; Corbo, Massimo; Eleopra, Roberto; Fazio, Raffaella; Filosto, Massimiliano; Giannini, Fabio; Granieri, Enrico; Bella, Vincenzo La; 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.

In: Journal of Neurology, Neurosurgery and Psychiatry, Vol. 86, No. 8, 2015, p. 879-886.

Research output: Contribution to journalArticle

Lauria, G, Bella, ED, Antonini, G, Borghero, G, Capasso, M, Caponnetto, C, Chiò, A, Corbo, M, Eleopra, R, Fazio, R, Filosto, M, Giannini, F, Granieri, E, Bella, VL, Logroscino, G, Mandrioli, J, Mazzini, L, Monsurrò, MR, Mora, G, Pietrini, V, Quatrale, R, Rizzi, R, Salvi, F, Siciliano, G, Sorarù, G, Volanti, P, Tramacere, I & Filippini, G 2015, 'Erythropoietin in amyotrophic lateral sclerosis: A multicentre, randomised, double blind, placebo controlled, phase III study', Journal of Neurology, Neurosurgery and Psychiatry, vol. 86, no. 8, pp. 879-886. https://doi.org/10.1136/jnnp-2014-308996
Lauria, Giuseppe ; Bella, Eleonora Dalla ; Antonini, Giovanni ; Borghero, Giuseppe ; Capasso, Margherita ; Caponnetto, Claudia ; Chiò, Adriano ; Corbo, Massimo ; Eleopra, Roberto ; Fazio, Raffaella ; Filosto, Massimiliano ; Giannini, Fabio ; Granieri, Enrico ; Bella, Vincenzo La ; 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. / Erythropoietin in amyotrophic lateral sclerosis : A multicentre, randomised, double blind, placebo controlled, phase III study. In: Journal of Neurology, Neurosurgery and Psychiatry. 2015 ; Vol. 86, No. 8. pp. 879-886.
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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 intentionto-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.",
author = "Giuseppe Lauria and Bella, {Eleonora Dalla} and Giovanni Antonini and Giuseppe Borghero and Margherita Capasso and Claudia Caponnetto and Adriano Chi{\`o} and Massimo Corbo and Roberto Eleopra and Raffaella Fazio and Massimiliano Filosto and Fabio Giannini and Enrico Granieri and Bella, {Vincenzo La} and Giancarlo Logroscino and Jessica Mandrioli and Letizia Mazzini and Monsurr{\`o}, {Maria Rosaria} and Gabriele Mora and Vladimiro Pietrini and Rocco Quatrale and Romana Rizzi and Fabrizio Salvi and Gabriele Siciliano and Gianni Sorar{\`u} and Paolo Volanti and Irene Tramacere and Graziella Filippini",
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TY - JOUR

T1 - Erythropoietin in amyotrophic lateral sclerosis

T2 - A multicentre, randomised, double blind, placebo controlled, phase III study

AU - Lauria, Giuseppe

AU - Bella, Eleonora Dalla

AU - Antonini, Giovanni

AU - Borghero, Giuseppe

AU - Capasso, Margherita

AU - Caponnetto, Claudia

AU - Chiò, Adriano

AU - Corbo, Massimo

AU - Eleopra, Roberto

AU - Fazio, Raffaella

AU - Filosto, Massimiliano

AU - Giannini, Fabio

AU - Granieri, Enrico

AU - Bella, Vincenzo La

AU - Logroscino, Giancarlo

AU - Mandrioli, Jessica

AU - Mazzini, Letizia

AU - Monsurrò, Maria Rosaria

AU - Mora, Gabriele

AU - Pietrini, Vladimiro

AU - Quatrale, Rocco

AU - Rizzi, Romana

AU - Salvi, Fabrizio

AU - Siciliano, Gabriele

AU - Sorarù, Gianni

AU - Volanti, Paolo

AU - Tramacere, Irene

AU - Filippini, Graziella

PY - 2015

Y1 - 2015

N2 - 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 intentionto-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.

AB - 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 intentionto-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.

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