High-dose erythropoietin in patients with progressive multiple sclerosis: A randomized, placebo-controlled, phase 2 trial

Karen Schreiber; Melinda Magyari; Finn Sellebjerg; Pernille Iversen; Ellen Garde; Camilla Gøbel Madsen; Lars Börnsen; Jeppe Romme Christensen; Rikke Ratzer; Hartwig Roman Siebner; Bjarne Laursen; Per Soelberg Sorensen

doi:10.1177/1352458516661048

High-dose erythropoietin in patients with progressive multiple sclerosis: A randomized, placebo-controlled, phase 2 trial

Karen Schreiber, Melinda Magyari, Finn Sellebjerg, Pernille Iversen, Ellen Garde, Camilla Gøbel Madsen, Lars Börnsen, Jeppe Romme Christensen, Rikke Ratzer, Hartwig Roman Siebner, Bjarne Laursen, Per Soelberg Sorensen

Department of Clinical Medicine

22 Citations (Scopus)

Abstract

BACKGROUND: Erythropoietin (EPO) is a part of an endogenous neuroprotective system in the brain and may address pathophysiological mechanisms in progressive multiple sclerosis (MS).

OBJECTIVE: To evaluate a treatment effect of EPO on progressive MS.

METHODS: This was a single-center, randomized, double-blind, placebo-controlled phase 2 trial, in which 52 patients with secondary or primary progressive MS were allocated to treatment with recombinant EPO (48,000 IU) or placebo, administered intravenously 17 times during 24 weeks. Patients had an Expanded Disability Status Score (EDSS) from 4 to 6.5 and clinical progression without relapses in the 2 preceding years. The primary outcome was the change in a composite measure of maximum gait distance, hand dexterity, and cognition from baseline to 24 weeks.

RESULTS: A total of 50 patients completed the study. Venesection was performed often but no thromboembolic events occurred. We found no difference in the primary outcome between the EPO and the placebo group using the intention-to-treat principle ( p = 0.22). None of the secondary outcomes, neither clinical nor magnetic resonance imaging (MRI) measures showed any significant differences.

CONCLUSION: This study provides class II evidence that treatment with high-dose EPO is not an effective treatment in patients with moderately advanced progressive MS.

Original language	English
Journal	Multiple Sclerosis
Volume	23
Issue number	5
Pages (from-to)	675-685
ISSN	1352-4585
DOIs	https://doi.org/10.1177/1352458516661048
Publication status	Published - 1 Apr 2017

Keywords

Adult
Brain/drug effects
Disability Evaluation
Disease Progression
Double-Blind Method
Erythropoietin/administration & dosage
Female
Humans
Magnetic Resonance Imaging/methods
Male
Middle Aged
Multiple Sclerosis/drug therapy
Treatment Outcome

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Schreiber, K., Magyari, M., Sellebjerg, F., Iversen, P., Garde, E., Madsen, C. G., Börnsen, L., Romme Christensen, J., Ratzer, R., Siebner, H. R., Laursen, B., & Soelberg Sorensen, P. (2017). High-dose erythropoietin in patients with progressive multiple sclerosis: A randomized, placebo-controlled, phase 2 trial. Multiple Sclerosis, 23(5), 675-685. https://doi.org/10.1177/1352458516661048

Schreiber, K, Magyari, M, Sellebjerg, F, Iversen, P, Garde, E, Madsen, CG, Börnsen, L, Romme Christensen, J, Ratzer, R, Siebner, HR, Laursen, B & Soelberg Sorensen, P 2017, 'High-dose erythropoietin in patients with progressive multiple sclerosis: A randomized, placebo-controlled, phase 2 trial', Multiple Sclerosis, vol. 23, no. 5, pp. 675-685. https://doi.org/10.1177/1352458516661048

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abstract = "BACKGROUND: Erythropoietin (EPO) is a part of an endogenous neuroprotective system in the brain and may address pathophysiological mechanisms in progressive multiple sclerosis (MS).OBJECTIVE: To evaluate a treatment effect of EPO on progressive MS.METHODS: This was a single-center, randomized, double-blind, placebo-controlled phase 2 trial, in which 52 patients with secondary or primary progressive MS were allocated to treatment with recombinant EPO (48,000 IU) or placebo, administered intravenously 17 times during 24 weeks. Patients had an Expanded Disability Status Score (EDSS) from 4 to 6.5 and clinical progression without relapses in the 2 preceding years. The primary outcome was the change in a composite measure of maximum gait distance, hand dexterity, and cognition from baseline to 24 weeks.RESULTS: A total of 50 patients completed the study. Venesection was performed often but no thromboembolic events occurred. We found no difference in the primary outcome between the EPO and the placebo group using the intention-to-treat principle ( p = 0.22). None of the secondary outcomes, neither clinical nor magnetic resonance imaging (MRI) measures showed any significant differences.CONCLUSION: This study provides class II evidence that treatment with high-dose EPO is not an effective treatment in patients with moderately advanced progressive MS.",

keywords = "Adult, Brain/drug effects, Disability Evaluation, Disease Progression, Double-Blind Method, Erythropoietin/administration & dosage, Female, Humans, Magnetic Resonance Imaging/methods, Male, Middle Aged, Multiple Sclerosis/drug therapy, Treatment Outcome",

author = "Karen Schreiber and Melinda Magyari and Finn Sellebjerg and Pernille Iversen and Ellen Garde and Madsen, {Camilla G{\o}bel} and Lars B{\"o}rnsen and {Romme Christensen}, Jeppe and Rikke Ratzer and Siebner, {Hartwig Roman} and Bjarne Laursen and {Soelberg Sorensen}, Per",

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T1 - High-dose erythropoietin in patients with progressive multiple sclerosis

T2 - A randomized, placebo-controlled, phase 2 trial

AU - Schreiber, Karen

AU - Magyari, Melinda

AU - Sellebjerg, Finn

AU - Iversen, Pernille

AU - Garde, Ellen

AU - Madsen, Camilla Gøbel

AU - Börnsen, Lars

AU - Romme Christensen, Jeppe

AU - Ratzer, Rikke

AU - Siebner, Hartwig Roman

AU - Laursen, Bjarne

AU - Soelberg Sorensen, Per

PY - 2017/4/1

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N2 - BACKGROUND: Erythropoietin (EPO) is a part of an endogenous neuroprotective system in the brain and may address pathophysiological mechanisms in progressive multiple sclerosis (MS).OBJECTIVE: To evaluate a treatment effect of EPO on progressive MS.METHODS: This was a single-center, randomized, double-blind, placebo-controlled phase 2 trial, in which 52 patients with secondary or primary progressive MS were allocated to treatment with recombinant EPO (48,000 IU) or placebo, administered intravenously 17 times during 24 weeks. Patients had an Expanded Disability Status Score (EDSS) from 4 to 6.5 and clinical progression without relapses in the 2 preceding years. The primary outcome was the change in a composite measure of maximum gait distance, hand dexterity, and cognition from baseline to 24 weeks.RESULTS: A total of 50 patients completed the study. Venesection was performed often but no thromboembolic events occurred. We found no difference in the primary outcome between the EPO and the placebo group using the intention-to-treat principle ( p = 0.22). None of the secondary outcomes, neither clinical nor magnetic resonance imaging (MRI) measures showed any significant differences.CONCLUSION: This study provides class II evidence that treatment with high-dose EPO is not an effective treatment in patients with moderately advanced progressive MS.

AB - BACKGROUND: Erythropoietin (EPO) is a part of an endogenous neuroprotective system in the brain and may address pathophysiological mechanisms in progressive multiple sclerosis (MS).OBJECTIVE: To evaluate a treatment effect of EPO on progressive MS.METHODS: This was a single-center, randomized, double-blind, placebo-controlled phase 2 trial, in which 52 patients with secondary or primary progressive MS were allocated to treatment with recombinant EPO (48,000 IU) or placebo, administered intravenously 17 times during 24 weeks. Patients had an Expanded Disability Status Score (EDSS) from 4 to 6.5 and clinical progression without relapses in the 2 preceding years. The primary outcome was the change in a composite measure of maximum gait distance, hand dexterity, and cognition from baseline to 24 weeks.RESULTS: A total of 50 patients completed the study. Venesection was performed often but no thromboembolic events occurred. We found no difference in the primary outcome between the EPO and the placebo group using the intention-to-treat principle ( p = 0.22). None of the secondary outcomes, neither clinical nor magnetic resonance imaging (MRI) measures showed any significant differences.CONCLUSION: This study provides class II evidence that treatment with high-dose EPO is not an effective treatment in patients with moderately advanced progressive MS.

KW - Adult

KW - Brain/drug effects

KW - Disability Evaluation

KW - Disease Progression

KW - Double-Blind Method

KW - Erythropoietin/administration & dosage

KW - Female

KW - Humans

KW - Magnetic Resonance Imaging/methods

KW - Male

KW - Middle Aged

KW - Multiple Sclerosis/drug therapy

KW - Treatment Outcome

U2 - 10.1177/1352458516661048

DO - 10.1177/1352458516661048

M3 - Journal article

C2 - 27481206

SN - 1352-4585

VL - 23

SP - 675

EP - 685

JO - Multiple Sclerosis

JF - Multiple Sclerosis

IS - 5

ER -

High-dose erythropoietin in patients with progressive multiple sclerosis: A randomized, placebo-controlled, phase 2 trial

Abstract

Keywords

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