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

on behalf of the FORWARD Study investigative group

Research output: Contribution to journalArticle

Abstract

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; 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.

Original languageEnglish (US)
Pages (from-to)1700-1713
Number of pages14
JournalHeadache
Volume59
Issue number10
DOIs
StatePublished - Nov 1 2019

Fingerprint

Migraine Disorders
Headache
onabotulinumtoxinA
topiramate
Therapeutics
Observation

Keywords

  • botulinum toxin
  • chronic migraine prevention
  • clinical utility
  • safety
  • topiramate

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

FORWARD Study : Evaluating the Comparative Effectiveness of OnabotulinumtoxinA and Topiramate for Headache Prevention in Adults With Chronic Migraine. / on behalf of the FORWARD Study investigative group.

In: Headache, Vol. 59, No. 10, 01.11.2019, p. 1700-1713.

Research output: Contribution to journalArticle

@article{7c1e830d1cbb4ad5be4fd2970dbfedf7,
title = "FORWARD Study: Evaluating the Comparative Effectiveness of OnabotulinumtoxinA and Topiramate for Headache Prevention in Adults With Chronic Migraine",
abstract = "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; 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.",
keywords = "botulinum toxin, chronic migraine prevention, clinical utility, safety, topiramate",
author = "{on behalf of the FORWARD Study investigative group} and Rothrock, {John F.} and Adams, {Aubrey Manack} and Lipton, {Richard B.} and Silberstein, {Stephen D.} and Esther Jo and Xiang Zhao and Blumenfeld, {Andrew M.}",
year = "2019",
month = "11",
day = "1",
doi = "10.1111/head.13653",
language = "English (US)",
volume = "59",
pages = "1700--1713",
journal = "Headache",
issn = "0017-8748",
publisher = "Wiley-Blackwell",
number = "10",

}

TY - JOUR

T1 - FORWARD Study

T2 - Evaluating the Comparative Effectiveness of OnabotulinumtoxinA and Topiramate for Headache Prevention in Adults With Chronic Migraine

AU - on behalf of the FORWARD Study investigative group

AU - Rothrock, John F.

AU - Adams, Aubrey Manack

AU - Lipton, Richard B.

AU - Silberstein, Stephen D.

AU - Jo, Esther

AU - Zhao, Xiang

AU - Blumenfeld, Andrew M.

PY - 2019/11/1

Y1 - 2019/11/1

N2 - 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; 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.

AB - 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; 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.

KW - botulinum toxin

KW - chronic migraine prevention

KW - clinical utility

KW - safety

KW - topiramate

UR - http://www.scopus.com/inward/record.url?scp=85074393048&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85074393048&partnerID=8YFLogxK

U2 - 10.1111/head.13653

DO - 10.1111/head.13653

M3 - Article

C2 - 31559634

AN - SCOPUS:85074393048

VL - 59

SP - 1700

EP - 1713

JO - Headache

JF - Headache

SN - 0017-8748

IS - 10

ER -