PMID- 31559634
OWN - NLM
STAT- MEDLINE
DCOM- 20200721
LR  - 20200721
IS  - 1526-4610 (Electronic)
IS  - 0017-8748 (Print)
IS  - 0017-8748 (Linking)
VI  - 59
IP  - 10
DP  - 2019 Nov
TI  - FORWARD Study: Evaluating the Comparative Effectiveness of OnabotulinumtoxinA and 
      Topiramate for Headache Prevention in Adults With Chronic Migraine.
PG  - 1700-1713
LID - 10.1111/head.13653 [doi]
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.
CI  - (c) 2019 The Authors. Headache: The Journal of Head and Face Pain published by 
      Wiley Periodicals, Inc. on behalf of American Headache Society.
FAU - Rothrock, John F
AU  - Rothrock JF
AD  - Department of Neurology, George Washington University School of Medicine, 
      Washington, DC, USA.
FAU - Adams, Aubrey Manack
AU  - Adams AM
AD  - Global Medical Affairs, Allergan plc, Irvine, CA, USA.
FAU - Lipton, Richard B
AU  - Lipton RB
AD  - Department of Neurology, Montefiore Headache Center, Albert Einstein College of 
      Medicine, Bronx, NY, USA.
FAU - Silberstein, Stephen D
AU  - Silberstein SD
AD  - Department of Neurology, Jefferson Headache Center, Philadelphia, PA, USA.
FAU - Jo, Esther
AU  - Jo E
AD  - Global Medical Affairs, Allergan plc, Irvine, CA, USA.
FAU - Zhao, Xiang
AU  - Zhao X
AD  - Department of Statistics, Pharmaceutical Product Development, Austin, TX, USA.
FAU - Blumenfeld, Andrew M
AU  - Blumenfeld AM
AD  - Department of Neurology, Headache Center of Southern California, The Neurology 
      Center, Carlsbad, CA, USA.
CN  - FORWARD Study investigative group
LA  - eng
SI  - ClinicalTrials.gov/NCT02191579
GR  - Allergan plc (Dublin, Ireland)/International
GR  - Allergan/International
GR  - Allergan plc/International
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20190926
PL  - United States
TA  - Headache
JT  - Headache
JID - 2985091R
RN  - 0H73WJJ391 (Topiramate)
RN  - EC 3.4.24.69 (Botulinum Toxins, Type A)
RN  - EC 3.4.24.69 (onabotulinum toxin A)
SB  - IM
MH  - Adult
MH  - Botulinum Toxins, Type A/*therapeutic use
MH  - Cross-Over Studies
MH  - Female
MH  - Headache/*prevention & control
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Migraine Disorders/*prevention & control
MH  - Topiramate/*therapeutic use
MH  - Treatment Outcome
PMC - PMC6899480
OTO - NOTNLM
OT  - botulinum toxin
OT  - chronic migraine prevention
OT  - clinical utility
OT  - safety
OT  - topiramate
EDAT- 2019/09/29 06:00
MHDA- 2020/07/22 06:00
PMCR- 2019/12/08
CRDT- 2019/09/28 06:00
PHST- 2019/07/12 00:00 [accepted]
PHST- 2019/09/29 06:00 [pubmed]
PHST- 2020/07/22 06:00 [medline]
PHST- 2019/09/28 06:00 [entrez]
PHST- 2019/12/08 00:00 [pmc-release]
AID - HEAD13653 [pii]
AID - 10.1111/head.13653 [doi]
PST - ppublish
SO  - Headache. 2019 Nov;59(10):1700-1713. doi: 10.1111/head.13653. Epub 2019 Sep 26.