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A Randomized Trial to Evaluate OnabotulinumtoxinA for Prevention of Headaches in Adolescents With Chronic Migraine

OBJECTIVE: As a post‐approval commitment, this dose‐ranging study was undertaken to evaluate efficacy and safety of onabotulinumtoxinA in adolescents. BACKGROUND: In adolescents, migraine is often undiagnosed or misdiagnosed and can present unique management challenges. OnabotulinumtoxinA was approv...

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Autores principales: Winner, Paul K., Kabbouche, Marielle, Yonker, Marcy, Wangsadipura, Veronica, Lum, Arlene, Brin, Mitchell F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065250/
https://www.ncbi.nlm.nih.gov/pubmed/32037549
http://dx.doi.org/10.1111/head.13754
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author Winner, Paul K.
Kabbouche, Marielle
Yonker, Marcy
Wangsadipura, Veronica
Lum, Arlene
Brin, Mitchell F.
author_facet Winner, Paul K.
Kabbouche, Marielle
Yonker, Marcy
Wangsadipura, Veronica
Lum, Arlene
Brin, Mitchell F.
author_sort Winner, Paul K.
collection PubMed
description OBJECTIVE: As a post‐approval commitment, this dose‐ranging study was undertaken to evaluate efficacy and safety of onabotulinumtoxinA in adolescents. BACKGROUND: In adolescents, migraine is often undiagnosed or misdiagnosed and can present unique management challenges. OnabotulinumtoxinA was approved for prevention of chronic migraine (CM) in adults in 2010. METHODS: This multicenter, double‐blind, parallel‐group, randomized trial assessed a single treatment of onabotulinumtoxinA (155 U or 74 U) vs placebo (intramuscular saline) administered via the recommended fixed‐dose fixed site paradigm in adolescents with CM aged 12 to <18 years. The primary efficacy measure was change in frequency of headache days from baseline at week 12; other measures included change in frequency of headache days at weeks 4 and 8 and change in frequency of severe headache days. Safety and tolerability were assessed. RESULTS: Of 125 randomized patients (onabotulinumtoxinA 155 U, n = 45; onabotulinumtoxinA 74 U, n = 43; placebo, n = 37), all were included in the primary efficacy analysis, and 115 (92.0%) completed the study. Lack of efficacy was the primary reason for discontinuing (n = 4; 3.2%); no patients discontinued because of adverse events. All treatments reduced frequency of headache days at week 12, with no significant differences between treatments. The mean (95% confidence interval) changes from baseline in the frequency of headache days during the 28‐day period ending at week 12 (primary endpoint) were −6.3 (−8.5, −4.2), −6.4 (−8.8, −4.0), and −6.8 (−9.6, −4.1) days in the onabotulinumtoxinA 155 U, onabotulinumtoxinA 74 U, and placebo groups, respectively (P ≥ .474). All treatments reduced frequency of severe headache days and were well‐tolerated; serious adverse events (n = 3) were considered unrelated to treatment and resolved without sequelae. The most commonly reported treatment‐emergent adverse events were neck pain (n = 8), upper respiratory tract infection (n = 7), migraine, and nasopharyngitis (n = 5 each). CONCLUSION: Although this study did not meet its efficacy endpoints, onabotulinumtoxinA was well tolerated in this adolescent population. Given previous data demonstrating the benefits of onabotulinumtoxinA in adults with CM, additional studies with design modifications, including adequate statistical power, to assess the efficacy of multiple treatment cycles of onabotulinumtoxinA for CM prevention in adolescents may be informative.
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spelling pubmed-70652502020-03-16 A Randomized Trial to Evaluate OnabotulinumtoxinA for Prevention of Headaches in Adolescents With Chronic Migraine Winner, Paul K. Kabbouche, Marielle Yonker, Marcy Wangsadipura, Veronica Lum, Arlene Brin, Mitchell F. Headache Research Submissions OBJECTIVE: As a post‐approval commitment, this dose‐ranging study was undertaken to evaluate efficacy and safety of onabotulinumtoxinA in adolescents. BACKGROUND: In adolescents, migraine is often undiagnosed or misdiagnosed and can present unique management challenges. OnabotulinumtoxinA was approved for prevention of chronic migraine (CM) in adults in 2010. METHODS: This multicenter, double‐blind, parallel‐group, randomized trial assessed a single treatment of onabotulinumtoxinA (155 U or 74 U) vs placebo (intramuscular saline) administered via the recommended fixed‐dose fixed site paradigm in adolescents with CM aged 12 to <18 years. The primary efficacy measure was change in frequency of headache days from baseline at week 12; other measures included change in frequency of headache days at weeks 4 and 8 and change in frequency of severe headache days. Safety and tolerability were assessed. RESULTS: Of 125 randomized patients (onabotulinumtoxinA 155 U, n = 45; onabotulinumtoxinA 74 U, n = 43; placebo, n = 37), all were included in the primary efficacy analysis, and 115 (92.0%) completed the study. Lack of efficacy was the primary reason for discontinuing (n = 4; 3.2%); no patients discontinued because of adverse events. All treatments reduced frequency of headache days at week 12, with no significant differences between treatments. The mean (95% confidence interval) changes from baseline in the frequency of headache days during the 28‐day period ending at week 12 (primary endpoint) were −6.3 (−8.5, −4.2), −6.4 (−8.8, −4.0), and −6.8 (−9.6, −4.1) days in the onabotulinumtoxinA 155 U, onabotulinumtoxinA 74 U, and placebo groups, respectively (P ≥ .474). All treatments reduced frequency of severe headache days and were well‐tolerated; serious adverse events (n = 3) were considered unrelated to treatment and resolved without sequelae. The most commonly reported treatment‐emergent adverse events were neck pain (n = 8), upper respiratory tract infection (n = 7), migraine, and nasopharyngitis (n = 5 each). CONCLUSION: Although this study did not meet its efficacy endpoints, onabotulinumtoxinA was well tolerated in this adolescent population. Given previous data demonstrating the benefits of onabotulinumtoxinA in adults with CM, additional studies with design modifications, including adequate statistical power, to assess the efficacy of multiple treatment cycles of onabotulinumtoxinA for CM prevention in adolescents may be informative. John Wiley and Sons Inc. 2020-02-09 2020-03 /pmc/articles/PMC7065250/ /pubmed/32037549 http://dx.doi.org/10.1111/head.13754 Text en © 2020 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals, Inc. on behalf of American Headache Society This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Research Submissions
Winner, Paul K.
Kabbouche, Marielle
Yonker, Marcy
Wangsadipura, Veronica
Lum, Arlene
Brin, Mitchell F.
A Randomized Trial to Evaluate OnabotulinumtoxinA for Prevention of Headaches in Adolescents With Chronic Migraine
title A Randomized Trial to Evaluate OnabotulinumtoxinA for Prevention of Headaches in Adolescents With Chronic Migraine
title_full A Randomized Trial to Evaluate OnabotulinumtoxinA for Prevention of Headaches in Adolescents With Chronic Migraine
title_fullStr A Randomized Trial to Evaluate OnabotulinumtoxinA for Prevention of Headaches in Adolescents With Chronic Migraine
title_full_unstemmed A Randomized Trial to Evaluate OnabotulinumtoxinA for Prevention of Headaches in Adolescents With Chronic Migraine
title_short A Randomized Trial to Evaluate OnabotulinumtoxinA for Prevention of Headaches in Adolescents With Chronic Migraine
title_sort randomized trial to evaluate onabotulinumtoxina for prevention of headaches in adolescents with chronic migraine
topic Research Submissions
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065250/
https://www.ncbi.nlm.nih.gov/pubmed/32037549
http://dx.doi.org/10.1111/head.13754
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