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FORWARD Study: Evaluating the Comparative Effectiveness of OnabotulinumtoxinA and Topiramate for Headache Prevention in Adults With Chronic Migraine

OBJECTIVE: To compare effectiveness of onabotulinumtoxinA and topiramate for chronic migraine (CM) prevention. BACKGROUND: The efficacy* of onabotulinumtoxinA and topiramate has been established in placebo‐controlled randomized clinical trials (*defined as the benefit of treatment under ideal condit...

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Autores principales: Rothrock, John F., Adams, Aubrey Manack, Lipton, Richard B., Silberstein, Stephen D., Jo, Esther, Zhao, Xiang, Blumenfeld, Andrew M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899480/
https://www.ncbi.nlm.nih.gov/pubmed/31559634
http://dx.doi.org/10.1111/head.13653
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author Rothrock, John F.
Adams, Aubrey Manack
Lipton, Richard B.
Silberstein, Stephen D.
Jo, Esther
Zhao, Xiang
Blumenfeld, Andrew M.
author_facet Rothrock, John F.
Adams, Aubrey Manack
Lipton, Richard B.
Silberstein, Stephen D.
Jo, Esther
Zhao, Xiang
Blumenfeld, Andrew M.
author_sort Rothrock, John F.
collection PubMed
description OBJECTIVE: To compare effectiveness of onabotulinumtoxinA and topiramate for chronic migraine (CM) prevention. BACKGROUND: The efficacy* of onabotulinumtoxinA and topiramate has been established in placebo‐controlled randomized clinical trials (*defined as the benefit of treatment under ideal conditions). The effectiveness* of the 2 preventive treatments, however, has not been established (*the benefit of treatment under real‐world conditions, representing a blend of efficacy and tolerability). METHODS: In this multicenter, randomized, parallel‐group, post‐authorization, open‐label prospective study (FORWARD; http://ClinicalTrials.gov, NCT02191579), we randomized adults with CM (1:1) to onabotulinumtoxinA 155 U every 12 weeks for 3 cycles or topiramate “immediate release” 50‐100 mg/day to week 36. Primary outcome measure was proportion of patients achieving ≥50% reduction in headache days (weeks 29‐32). Missing values were imputed using baseline observation carried forward (BOCF) methodology. After 12 weeks, patients initially randomized to topiramate could cross over to onabotulinumtoxinA treatment. We monitored and recorded all adverse events (AEs). RESULTS: We enrolled 282 patients (onabotulinumtoxinA, n = 140; topiramate, n = 142) and 148 patients completed randomized treatment (onabotulinumtoxinA, n = 120 [86%]; topiramate, n = 28 [20%]). Primary reasons for withdrawal were ineffective treatment (onabotulinumtoxinA, n = 7 [5%]; topiramate, n = 27 [19%]) and AEs (onabotulinumtoxinA, n = 5 [4%]; topiramate, n = 72 [51%]). Eighty topiramate patients crossed over to onabotulinumtoxinA. In the BOCF analysis, a significantly higher proportion of patients randomized to onabotulinumtoxinA experienced ≥50% reduction in headache frequency compared with those randomized to topiramate (40% [56/140] vs 12% [17/142], respectively; adjusted OR, 4.9 [95% CI, 2.7‐9.1]; P < .001). OnabotulinumtoxinA was superior to topiramate in meeting secondary endpoints. In a post hoc analysis using observed data, the 50% responder rates at week 12 were 45.6% for onabotulinumtoxinA (n = 125) and 29.4% for topiramate (n = 109) (P = .015). AEs were reported by 48% (105/220) of onabotulinumtoxinA and 79% (112/142) of topiramate patients. Results were similar in those who crossed over to onabotulinumtoxinA. CONCLUSIONS: While using imputation methods of accounting for differences in discontinuation rates, we found onabotulinumtoxinA to have greater clinical utility than topiramate, largely because of tolerability issues associated with the latter and a relatively higher number of onabotulinumtoxinA patients remaining on treatment.
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spelling pubmed-68994802019-12-19 FORWARD Study: Evaluating the Comparative Effectiveness of OnabotulinumtoxinA and Topiramate for Headache Prevention in Adults With Chronic Migraine Rothrock, John F. Adams, Aubrey Manack Lipton, Richard B. Silberstein, Stephen D. Jo, Esther Zhao, Xiang Blumenfeld, Andrew M. Headache Research Submissions OBJECTIVE: To compare effectiveness of onabotulinumtoxinA and topiramate for chronic migraine (CM) prevention. BACKGROUND: The efficacy* of onabotulinumtoxinA and topiramate has been established in placebo‐controlled randomized clinical trials (*defined as the benefit of treatment under ideal conditions). The effectiveness* of the 2 preventive treatments, however, has not been established (*the benefit of treatment under real‐world conditions, representing a blend of efficacy and tolerability). METHODS: In this multicenter, randomized, parallel‐group, post‐authorization, open‐label prospective study (FORWARD; http://ClinicalTrials.gov, NCT02191579), we randomized adults with CM (1:1) to onabotulinumtoxinA 155 U every 12 weeks for 3 cycles or topiramate “immediate release” 50‐100 mg/day to week 36. Primary outcome measure was proportion of patients achieving ≥50% reduction in headache days (weeks 29‐32). Missing values were imputed using baseline observation carried forward (BOCF) methodology. After 12 weeks, patients initially randomized to topiramate could cross over to onabotulinumtoxinA treatment. We monitored and recorded all adverse events (AEs). RESULTS: We enrolled 282 patients (onabotulinumtoxinA, n = 140; topiramate, n = 142) and 148 patients completed randomized treatment (onabotulinumtoxinA, n = 120 [86%]; topiramate, n = 28 [20%]). Primary reasons for withdrawal were ineffective treatment (onabotulinumtoxinA, n = 7 [5%]; topiramate, n = 27 [19%]) and AEs (onabotulinumtoxinA, n = 5 [4%]; topiramate, n = 72 [51%]). Eighty topiramate patients crossed over to onabotulinumtoxinA. In the BOCF analysis, a significantly higher proportion of patients randomized to onabotulinumtoxinA experienced ≥50% reduction in headache frequency compared with those randomized to topiramate (40% [56/140] vs 12% [17/142], respectively; adjusted OR, 4.9 [95% CI, 2.7‐9.1]; P < .001). OnabotulinumtoxinA was superior to topiramate in meeting secondary endpoints. In a post hoc analysis using observed data, the 50% responder rates at week 12 were 45.6% for onabotulinumtoxinA (n = 125) and 29.4% for topiramate (n = 109) (P = .015). AEs were reported by 48% (105/220) of onabotulinumtoxinA and 79% (112/142) of topiramate patients. Results were similar in those who crossed over to onabotulinumtoxinA. CONCLUSIONS: While using imputation methods of accounting for differences in discontinuation rates, we found onabotulinumtoxinA to have greater clinical utility than topiramate, largely because of tolerability issues associated with the latter and a relatively higher number of onabotulinumtoxinA patients remaining on treatment. John Wiley and Sons Inc. 2019-09-26 2019 /pmc/articles/PMC6899480/ /pubmed/31559634 http://dx.doi.org/10.1111/head.13653 Text en © 2019 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
Rothrock, John F.
Adams, Aubrey Manack
Lipton, Richard B.
Silberstein, Stephen D.
Jo, Esther
Zhao, Xiang
Blumenfeld, Andrew M.
FORWARD Study: Evaluating the Comparative Effectiveness of OnabotulinumtoxinA and Topiramate for Headache Prevention in Adults With Chronic Migraine
title FORWARD Study: Evaluating the Comparative Effectiveness of OnabotulinumtoxinA and Topiramate for Headache Prevention in Adults With Chronic Migraine
title_full FORWARD Study: Evaluating the Comparative Effectiveness of OnabotulinumtoxinA and Topiramate for Headache Prevention in Adults With Chronic Migraine
title_fullStr FORWARD Study: Evaluating the Comparative Effectiveness of OnabotulinumtoxinA and Topiramate for Headache Prevention in Adults With Chronic Migraine
title_full_unstemmed FORWARD Study: Evaluating the Comparative Effectiveness of OnabotulinumtoxinA and Topiramate for Headache Prevention in Adults With Chronic Migraine
title_short FORWARD Study: Evaluating the Comparative Effectiveness of OnabotulinumtoxinA and Topiramate for Headache Prevention in Adults With Chronic Migraine
title_sort forward study: evaluating the comparative effectiveness of onabotulinumtoxina and topiramate for headache prevention in adults with chronic migraine
topic Research Submissions
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899480/
https://www.ncbi.nlm.nih.gov/pubmed/31559634
http://dx.doi.org/10.1111/head.13653
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