FORWARD Study: Evaluating the Comparative Effectiveness of OnabotulinumtoxinA and Topiramate for Headache Prevention in Adults With Chronic Migraine
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Published on: June 2, 2014
John F Rothrock1, Aubrey Manack Adams2, Richard B Lipton3
1Department of Neurology, George Washington University School of Medicine, Washington, DC, USA.
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.
Insights
OnabotulinumtoxinA demonstrated superior effectiveness and tolerability compared to topiramate for chronic migraine prevention in real-world conditions. More patients on onabotulinumtoxinA achieved significant headache reduction with fewer adverse events.
Area of Science:
- Neurology
- Pharmacology
Background:
- The efficacy of onabotulinumtoxinA and topiramate for chronic migraine (CM) is established in ideal conditions.
- Real-world effectiveness, combining efficacy and tolerability, requires further investigation for these CM treatments.
Purpose of the Study:
- To compare the real-world effectiveness of onabotulinumtoxinA versus topiramate for the prevention of chronic migraine.
- To evaluate treatment tolerability and patient retention in a prospective, open-label study.
Main Methods:
- A multicenter, randomized, open-label study (FORWARD) comparing onabotulinumtoxinA (155 U every 12 weeks) to topiramate (50-100 mg/day) for CM prevention.
- The primary outcome was the proportion of patients achieving ≥50% reduction in headache days from weeks 29-32, using baseline observation carried forward (BOCF) for missing data.
- Adverse events (AEs) and treatment discontinuation rates were monitored, with a crossover option from topiramate to onabotulinumtoxinA after 12 weeks.
Main Results:
- OnabotulinumtoxinA treatment resulted in a significantly higher proportion of patients achieving ≥50% headache reduction (40% vs. 12%, P < .001) compared to topiramate in the BOCF analysis.
- Treatment discontinuation due to adverse events was substantially higher for topiramate (51%) than for onabotulinumtoxinA (4%).
- OnabotulinumtoxinA showed superior effectiveness and tolerability, with 86% of patients completing treatment compared to 20% for topiramate.
Conclusions:
- OnabotulinumtoxinA exhibits greater clinical utility for chronic migraine prevention than topiramate, primarily due to better tolerability.
- The higher rate of patients remaining on treatment with onabotulinumtoxinA contributes to its overall effectiveness in real-world settings.
- These findings support onabotulinumtoxinA as a preferred option for chronic migraine management, considering both efficacy and patient experience.
