A Multi‐Center Double‐Blind Pilot Comparison of OnabotulinumtoxinA and Topiramate for the Prophylactic Treatment of Chronic Migraine

Abstract

Objective.-This multi-center pilot study compared the efficacy of onabotulinumtoxinA with topiramate (a Food and Drug Administration approved and widely accepted treatment for prevention of migraine) in individuals with chronic migraine (CM).Methods.-A total of 59 subjects with CM were randomly assigned to one of 2 groups: Group 1 (n = 30) received topiramate plus placebo injections, Group 2 (n = 29) received onabotulinumtoxinA injections plus placebo tablets. Subjects maintained daily headache diaries over a 4-week baseline period and a 12-week active study period. The primary endpoint was the Physician Global Assessment, which measured the treatment responder rate and indicated improvement in both groups over 12 weeks. Secondary endpoints, measured at weeks 4 and 12, included headache days per month, migraine days, headachefree days, days on acute medication, severity of headache episodes, Migraine Impact & Disability Assessment, Headache Impact Test, effectiveness of and satisfaction with current treatment on the amount of medication needed, and the frequency and severity of migraine symptoms. At 12 weeks subjects were re-evaluated and tapered off oral study medications over a 2-week time period. Subjects not reporting a >50% reduction of headache frequency at 12 weeks were invited to participate in a 12-week open label extension study with onabotulinumtoxinA. Of these, 20 subjects, 9 from the Topiramate Group and 11 from the OnabotulinumtoxinA Group, volunteered for this extension from weeks 14 to 26.Results.-This study demonstrated positive benefit for both onabotulinumtoxinA and topiramate in subjects with CM. Overall, the results were statistically significant within groups but not between groups. By week 26, subjects had a reduction of headache days per month compared with baseline. This was a significant within-group finding.Conclusion.-OnabotulinumtoxinA and topiramate demonstrated similar efficacy for subjects with CM as determined by Global Physician Assessment and supported by multiple secondary endpoint measures.

Assessing Clinically Meaningful Treatment Effects in Controlled Trials: Chronic Migraine as an Example

“…10,31 Although these 2 studies are vastly underpowered, they provide the opportunity to directly compare outcome measures and safety and tolerability of each treatment. The first study was a single-center, 2-arm, double-blind, double-dummy study.…”

Chronic Migraine

“…69 Both drugs significantly reduced the number of headache days and neither was statistically superior to the other, which likely reflects the fact that the study was underpowered for this endpoint. However, onabotulinumtoxinA was associated with improvement in sleep, recreation, mood, presenteeism, and absenteeism relative to topiramate, and was much better tolerated.…”

“…The mean reduction of monthly headache days was 5.8 for topiramate vs 4.7 days for placebo. 69 In another study, topiramate was not superior to placebo in preventing the transformation of EM to CM. 72 While topiramate may be useful both adjunctively and as a solo intervention in CM, its preferred role is in frequent EM.…”

Update on Medication-Overuse Headache and Its Treatment

“…The comparative efficacy and safety of these two approaches for chronic migraine were evaluated in two studies [65,66]. Both drugs proved equally effective in improving several pain/disability parameters, but the safety profile was higher for onabotulinumtoxinA and the discontinuation rate significantly higher for topiramate [adverse events (AEs) being the major reason for withdrawal] (discontinuation rates 25-44.2 % for topiramate; 10-25 % for onabotulinumtoxinA) [12,[65][66][67][68][69].…”