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Efficacy and safety of abobotulinumtoxinA in spastic lower limb: Randomized trial and extension

OBJECTIVE: To demonstrate single abobotulinumtoxinA injection efficacy in lower limb vs placebo for adults with chronic hemiparesis and assess long-term safety and efficacy of repeated injections. METHODS: In a multicenter, double-blind, randomized, placebo-controlled, single-cycle study followed by...

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Autores principales: Gracies, Jean-Michel, Esquenazi, Alberto, Brashear, Allison, Banach, Marta, Kocer, Serdar, Jech, Robert, Khatkova, Svetlana, Benetin, Ján, Vecchio, Michele, McAllister, Peter, Ilkowski, Jan, Ochudlo, Stanislaw, Catus, France, Grandoulier, Anne Sophie, Vilain, Claire, Picaut, Philippe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705248/
https://www.ncbi.nlm.nih.gov/pubmed/29093068
http://dx.doi.org/10.1212/WNL.0000000000004687
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author Gracies, Jean-Michel
Esquenazi, Alberto
Brashear, Allison
Banach, Marta
Kocer, Serdar
Jech, Robert
Khatkova, Svetlana
Benetin, Ján
Vecchio, Michele
McAllister, Peter
Ilkowski, Jan
Ochudlo, Stanislaw
Catus, France
Grandoulier, Anne Sophie
Vilain, Claire
Picaut, Philippe
author_facet Gracies, Jean-Michel
Esquenazi, Alberto
Brashear, Allison
Banach, Marta
Kocer, Serdar
Jech, Robert
Khatkova, Svetlana
Benetin, Ján
Vecchio, Michele
McAllister, Peter
Ilkowski, Jan
Ochudlo, Stanislaw
Catus, France
Grandoulier, Anne Sophie
Vilain, Claire
Picaut, Philippe
author_sort Gracies, Jean-Michel
collection PubMed
description OBJECTIVE: To demonstrate single abobotulinumtoxinA injection efficacy in lower limb vs placebo for adults with chronic hemiparesis and assess long-term safety and efficacy of repeated injections. METHODS: In a multicenter, double-blind, randomized, placebo-controlled, single-cycle study followed by a 1-year open-label, multiple-cycle extension, adults ≥6 months after stroke/brain injury received one lower limb injection (abobotulinumtoxinA 1,000 U, abobotulinumtoxinA 1,500 U, placebo) followed by ≤4 open-label cycles (1,000, 1,500 U) at ≥12-week intervals. Efficacy measures included Modified Ashworth Scale (MAS) in gastrocnemius–soleus complex (GSC; double-blind primary endpoint), physician global assessment (PGA), and comfortable barefoot walking speed. Safety was the open-label primary endpoint. RESULTS: After a single injection, mean (95% confidence interval) MAS GSC changes from baseline at week 4 (double-blind, n = 381) were as follows: −0.5 (−0.7 to −0.4) (placebo, n = 128), −0.6 (−0.8 to −0.5) (abobotulinumtoxinA 1,000 U, n = 125; p = 0.28 vs placebo), and −0.8 (−0.9 to −0.7) (abobotulinumtoxinA 1,500 U, n = 128; p = 0.009 vs placebo). Mean week 4 PGA scores were as follows: 0.7 (0.5, 0.9) (placebo), 0.9 (0.7, 1.1) (1,000 U; p = 0.067 vs placebo), and 0.9 (0.7, 1.1) (1,500 U; p = 0.067); walking speed was not significantly improved vs placebo. At cycle 4, week 4 (open-label), mean MAS GSC change reached −1.0. Incremental improvements in PGA and walking speed occurred across open-label cycles; by cycle 4, week 4, mean PGA was 1.9, and walking speed increased +25.3% (17.5, 33.2), with 16% of participants walking >0.8 m/s (associated with community mobility; 0% at baseline). Tolerability was good and consistent with the known abobotulinumtoxinA safety profile. CONCLUSIONS: In chronic hemiparesis, single abobotulinumtoxinA (Dysport Ipsen) administration reduced muscle tone. Repeated administration over a year was well-tolerated and improved walking speed and likelihood of achieving community ambulation. CLINICALTRIAL.GOV IDENTIFIERS: NCT01249404, NCT01251367. CLASSIFICATION OF EVIDENCE: The double-blind phase of this study provides Class I evidence that for adults with chronic spastic hemiparesis, a single abobotulinumtoxinA injection reduces lower extremity muscle tone.
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spelling pubmed-57052482017-12-07 Efficacy and safety of abobotulinumtoxinA in spastic lower limb: Randomized trial and extension Gracies, Jean-Michel Esquenazi, Alberto Brashear, Allison Banach, Marta Kocer, Serdar Jech, Robert Khatkova, Svetlana Benetin, Ján Vecchio, Michele McAllister, Peter Ilkowski, Jan Ochudlo, Stanislaw Catus, France Grandoulier, Anne Sophie Vilain, Claire Picaut, Philippe Neurology Article OBJECTIVE: To demonstrate single abobotulinumtoxinA injection efficacy in lower limb vs placebo for adults with chronic hemiparesis and assess long-term safety and efficacy of repeated injections. METHODS: In a multicenter, double-blind, randomized, placebo-controlled, single-cycle study followed by a 1-year open-label, multiple-cycle extension, adults ≥6 months after stroke/brain injury received one lower limb injection (abobotulinumtoxinA 1,000 U, abobotulinumtoxinA 1,500 U, placebo) followed by ≤4 open-label cycles (1,000, 1,500 U) at ≥12-week intervals. Efficacy measures included Modified Ashworth Scale (MAS) in gastrocnemius–soleus complex (GSC; double-blind primary endpoint), physician global assessment (PGA), and comfortable barefoot walking speed. Safety was the open-label primary endpoint. RESULTS: After a single injection, mean (95% confidence interval) MAS GSC changes from baseline at week 4 (double-blind, n = 381) were as follows: −0.5 (−0.7 to −0.4) (placebo, n = 128), −0.6 (−0.8 to −0.5) (abobotulinumtoxinA 1,000 U, n = 125; p = 0.28 vs placebo), and −0.8 (−0.9 to −0.7) (abobotulinumtoxinA 1,500 U, n = 128; p = 0.009 vs placebo). Mean week 4 PGA scores were as follows: 0.7 (0.5, 0.9) (placebo), 0.9 (0.7, 1.1) (1,000 U; p = 0.067 vs placebo), and 0.9 (0.7, 1.1) (1,500 U; p = 0.067); walking speed was not significantly improved vs placebo. At cycle 4, week 4 (open-label), mean MAS GSC change reached −1.0. Incremental improvements in PGA and walking speed occurred across open-label cycles; by cycle 4, week 4, mean PGA was 1.9, and walking speed increased +25.3% (17.5, 33.2), with 16% of participants walking >0.8 m/s (associated with community mobility; 0% at baseline). Tolerability was good and consistent with the known abobotulinumtoxinA safety profile. CONCLUSIONS: In chronic hemiparesis, single abobotulinumtoxinA (Dysport Ipsen) administration reduced muscle tone. Repeated administration over a year was well-tolerated and improved walking speed and likelihood of achieving community ambulation. CLINICALTRIAL.GOV IDENTIFIERS: NCT01249404, NCT01251367. CLASSIFICATION OF EVIDENCE: The double-blind phase of this study provides Class I evidence that for adults with chronic spastic hemiparesis, a single abobotulinumtoxinA injection reduces lower extremity muscle tone. Lippincott Williams & Wilkins 2017-11-28 /pmc/articles/PMC5705248/ /pubmed/29093068 http://dx.doi.org/10.1212/WNL.0000000000004687 Text en Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Article
Gracies, Jean-Michel
Esquenazi, Alberto
Brashear, Allison
Banach, Marta
Kocer, Serdar
Jech, Robert
Khatkova, Svetlana
Benetin, Ján
Vecchio, Michele
McAllister, Peter
Ilkowski, Jan
Ochudlo, Stanislaw
Catus, France
Grandoulier, Anne Sophie
Vilain, Claire
Picaut, Philippe
Efficacy and safety of abobotulinumtoxinA in spastic lower limb: Randomized trial and extension
title Efficacy and safety of abobotulinumtoxinA in spastic lower limb: Randomized trial and extension
title_full Efficacy and safety of abobotulinumtoxinA in spastic lower limb: Randomized trial and extension
title_fullStr Efficacy and safety of abobotulinumtoxinA in spastic lower limb: Randomized trial and extension
title_full_unstemmed Efficacy and safety of abobotulinumtoxinA in spastic lower limb: Randomized trial and extension
title_short Efficacy and safety of abobotulinumtoxinA in spastic lower limb: Randomized trial and extension
title_sort efficacy and safety of abobotulinumtoxina in spastic lower limb: randomized trial and extension
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705248/
https://www.ncbi.nlm.nih.gov/pubmed/29093068
http://dx.doi.org/10.1212/WNL.0000000000004687
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