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.

Erythropoietin in amyotrophic lateral sclerosis: A multicentre, randomised, double blind, placebo controlled, phase III study / Lauria, G.; Dalla Bella, E.; Antonini, G.; Borghero, G.; Capasso, M.; Caponnetto, C.; Chio, A.; Corbo, M.; Eleopra, R.; Fazio, R.; Filosto, M.; Giannini, F.; Granieri, E.; La Bella, V.; Logroscino, G.; Mandrioli, J.; Mazzini, L.; Monsurro, M. R.; Mora, G.; Pietrini, V.; Quatrale, R.; Rizzi, R.; Salvi, F.; Siciliano, G.; Soraru, G.; Volanti, P.; Tramacere, I.; Filippini, G.; Cazzato, D.; Cesnik, E.; Groppo, E.; Sette, E.; Pani, C.; Costantino, E.; Orlandini, F.; Boi, D.; Querin, G.; D'Ascenzo, C.; Sagnelli, A.; Piccirillo, G.; Aiello, Marina; Chetta, Alfredo Antonio; Grassi, A.; Lunetta, C.; Maestri, E.; Padovani, A.; Cotelli, M.; Todeschini, A.; Morino, S.; Di Pasquale, A.; Latino, P.; Casali, S.; Battistini, S.; Pirrelli, M.; Cantello, R.; Nasuelli, N.; Servo, S.; De Gennaro, R.; Gastaldo, E.; Georgoulopoulou, E.; Fini, N.; Taiello, A. C.; Colletti, T.; Calvo, A.; Moglia, C.; Fuda, G.; Marinou, K.; Riva, N.; Cerri, F.; Lopez, I. D.; De Cicco, D.; Battaglia, G.; Marcello, N.; Rinaldi, M.; Scialo, C.; Mantero, V.; Mascolo, M.; Carlesi, C.; Ienco, E. C.; Di Muzio, A.; Verriello, L.; D'Amico, D.; Simone, I. L.; Tortelli, R.; Cortese, R.; Bartolomei, I.. - In: JOURNAL OF NEUROLOGY, NEUROSURGERY AND PSYCHIATRY. - ISSN 0022-3050. - 86:8(2015), pp. 879-886. [10.1136/jnnp-2014-308996]

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

Pietrini, V.;AIELLO, Marina;CHETTA, Alfredo Antonio;
2015-01-01

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.
2015
Erythropoietin in amyotrophic lateral sclerosis: A multicentre, randomised, double blind, placebo controlled, phase III study / Lauria, G.; Dalla Bella, E.; Antonini, G.; Borghero, G.; Capasso, M.; Caponnetto, C.; Chio, A.; Corbo, M.; Eleopra, R.; Fazio, R.; Filosto, M.; Giannini, F.; Granieri, E.; La Bella, V.; Logroscino, G.; Mandrioli, J.; Mazzini, L.; Monsurro, M. R.; Mora, G.; Pietrini, V.; Quatrale, R.; Rizzi, R.; Salvi, F.; Siciliano, G.; Soraru, G.; Volanti, P.; Tramacere, I.; Filippini, G.; Cazzato, D.; Cesnik, E.; Groppo, E.; Sette, E.; Pani, C.; Costantino, E.; Orlandini, F.; Boi, D.; Querin, G.; D'Ascenzo, C.; Sagnelli, A.; Piccirillo, G.; Aiello, Marina; Chetta, Alfredo Antonio; Grassi, A.; Lunetta, C.; Maestri, E.; Padovani, A.; Cotelli, M.; Todeschini, A.; Morino, S.; Di Pasquale, A.; Latino, P.; Casali, S.; Battistini, S.; Pirrelli, M.; Cantello, R.; Nasuelli, N.; Servo, S.; De Gennaro, R.; Gastaldo, E.; Georgoulopoulou, E.; Fini, N.; Taiello, A. C.; Colletti, T.; Calvo, A.; Moglia, C.; Fuda, G.; Marinou, K.; Riva, N.; Cerri, F.; Lopez, I. D.; De Cicco, D.; Battaglia, G.; Marcello, N.; Rinaldi, M.; Scialo, C.; Mantero, V.; Mascolo, M.; Carlesi, C.; Ienco, E. C.; Di Muzio, A.; Verriello, L.; D'Amico, D.; Simone, I. L.; Tortelli, R.; Cortese, R.; Bartolomei, I.. - In: JOURNAL OF NEUROLOGY, NEUROSURGERY AND PSYCHIATRY. - ISSN 0022-3050. - 86:8(2015), pp. 879-886. [10.1136/jnnp-2014-308996]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2816279
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