February 8, 2023

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).

In the january issue of headache dr. roger kadyan colleagues report the results from the clinical study comparing on a botulinum toxin a and topiramate for the treatment of chronic migraine given the recent fda approval of ona botulinum toxin a for the prophylactic treatment of chronic migraine head-to-head studies of own a botulinum toxin a with other chronic

Migraine therapies are essential such studies comparing benefits and tolerability of prophylactic treatments will help clinicians to determine optimal therapy for their patients dr. katy joins us today to discuss this trial of own a botulinum toxin a versus topiramate for the prophylaxis of chronic migraine well thank you for speaking with me today dr. katie well

I’m happy to do so todd so could you please begin by telling us what your motivation was for comparing on a botulinum toxin a with topiramate for the prophylactic treatment of chronic migraine yeah there’s actually two motivations that i had in designing this study the first of these was that you know in clinical practice i was seeing results of using on the

Botulinum as being more effective as a preventive treatment for chronic migraine then at that point in time i was seeing being reported in the literature and so i was really curious about why that difference was occurring and you know i began thinking about it the second part of that motivation was that i kind of wondered whether it was in part that in clinical

Practice we use a different set of observation skills then we often do in in standard research trials when migraine prophylaxis so that was really the motivation behind the study right what types of patients did you include in the study well this was a three center study there were 59 patients and basically these were individuals who had although we didn’t have the

Clear definition when we started this study they had chronic migraine they had a significant number of headaches over 20 in a month’s time and you know all of them obviously having migraine not necessarily every one of those 20 being meeting all criteria for migraine so it kind of fit into that appendix definition that came out a little bit later you tell us a bit

About your study design specifically how you kept subjects blinded as to whether or not they were receiving injectable on a botulinum toxin a as compared to the world to faerymate yeah where was your well aware that’s kind of a challenge but what we did in this particular study is we had 59 subjects they were naive and they were randomized into two groups group

1 received topiramate plus placebo injections while group two new received placebo topiramate plus active on a botulinum and we kept the injector and the coordinator blinded to which which was being used we had a nurse basically signed to doing nothing but maintaining the blind in the study and she wasn’t involved with the patients then that people prior to this

Had gone through a four-week run in period that’s how we establish the baseline frequency of their headache and then we followed them through 12 weeks in the active phase and then those who had a non-response meaning less than fifty percent reduction in their migraines and we’re on topiramate they had an option to go into open-label with on a botulinum however

That group turned out to be pretty small so although it’s reported on briefly in the paper it’s really much more of an exploratory component of this study just because of the very small size that continued i see okay and what were your main outcome measures that used well this i think is part of the uniqueness of this study because again what i was trying to do is

Explore you know what we saw on the clinic versus what was reported in many different clinical trials and so what i ended up using as a primary endpoint is the physician global assessment that’s a nine point scale where zero is no change and then you go up by increments of 25% to slight mild marked or complete improvement and then the same type of scale goes on

The down side with slight worsening moderate worsening etc so it’s actually turns out to be a nine-point scale and the physician the investigator assigns the number to each patient yet their visit and so what were your findings are both in regards to benefits as well as side effects yeah well let me just mention i should tell you to a little bit about secondary

Endpoints because you know i was trying to validate this idea of physician global assessment but on secondary measures we used a lot of the traditional measures we looked at headache days we looked at migraine days headache free days days with the use of acute medication headache severity and we looked at midas and hit and then in addition to that i put in a number

Of other endpoints that i think are somewhat non-traditional mostly focusing on quality of life but in those endpoints although there could be no statistical assignment to this it was just observation we looked at money spent on my grain per month we looked at the concept of presenteeism which was self rated we look to interference with work change in sleep mood

Performance of daily recreational activities and something we called enjoyment of light so we collected a lot of data and what i wanted to do was to really get a global assessment of how patients the two in the two study groups did through the 12-week period that they were in the active phase of the study of course obviously we did safety assessments as well is

It what were your findings well a very interestingly you know by four weeks the topiramate group seventy-four percent had shown positive change by physician global assessment and at 12 weeks there were 70 point eight percent who maintained a positive benefit as sess by physician global assessment scores for the only botulinum group at four weeks it was 61 and at

12 weeks that went up to seventy nine percent showing improvement on the more traditional endpoints and headed days there was a reduction for both groups that was quite similar we had four topiramate 4.4 at the four-week period of time in three thrown botulinum and then interestingly by the 12-week point time point 8.14 topiramate and 12.44 on a botulinum these

Difference were statistically significant both of these in terms of the intergroup view but we didn’t have a placebo in this we were just using the comparator study also we saw significant changes in migraine days the number of headache day etic three days increased again significant from baseline a headache severity improved minus scores decreased for topiramate 26

Points at 12 weeks and for the ona botulinum they decreased by 38 points so those were quite significant in my mind then when i looked at these non-traditional endpoints again i think this is really relevant to clinicians we saw a decrease in money spent on migraine for the topiramate group 121 dollars versus some almost five hundred dollars 197 dollars or than one

Abacha lynam group we saw significant improvements and presenteeism interference with migraine and work sleep mood performance of daily activities recreational activities enjoyment of life when i say significant i don’t mean that in a statistical sense but in a very clinical sense there was marked improvement reported there in terms of safety both of these therapies

Were well tolerated we didn’t have any serious adverse events in either group and you know the types of adverse events we saw we’re pretty predictable in terms of those associated with topiramate and i think we had one or two people that had some very minor motor changes that were significant or were a ease in the ona botulinum but by and large bore therapies were

Very very well tolerated did you find that you’re less traditional outcomes do they associate with the more traditional outcome measures well i think they did and i think it all supports the idea of physician global assessment one of the things that i tried to raise as a question for the headache community to think about is really the methodology by which we study

Migraine prevention you know i think historically we’ve always used this reduction of fifty percent or more of migraine attacks you know it’s kind of a historical measure but you know not one with a lot of scientific basis it is one with a lot of consensus and historical basis more recently it’s been changed to headache days which may be a lot easier to measure but

In the clinic of course we look at things in a much broader perspective in deciding the impact and i would argue that the medications and treatments we most often use are affecting a person’s physiological function not only during a tax of migraine but also between attacks of migraine and so there may be value in taking a more global assessment of patient response

And i think in the article i gave the idea that if somebody had a forty percent reduction in headache days we probably you know by traditional standards would say that person failed but if we took a global assessment of that person in our clinic and saw the same forty percent reduction but that they’re using less acute treatment medicines that are sleeping better

They’re attending to their work better their mood is improved they tell you that they’re enjoying their life much more with the utilization of these medication we would be likely defining that person as a success and so you know i think when i look at this study from a broad perspective it really does support the idea of physician global assessment and i think the

Non-traditional quality of life that i mentioned clearly support reasons as to why we might see a better clinical response and of course a study when it was done the preamp study hadn’t been published yet but that study of course gave us a good scientific foundation or basis for the use of ona botulinum as well but again i think the uniqueness of this study is

That broad perspective in using in using an assessing patient response and in your opinion are there other ways that a clinician could use the results from your study when making treatment decisions about their chronic migraine patients well again i think this study does fall in line with what was seen in the preamp study and i think obviously the preamp study is a

Much larger much more scientifically sound study based on the size particularly but i would argue that you know what this does is encourage physicians to use their assessments to take a more global view of patient response and perhaps not just for ona botulinum but for many of the treatments that we use and in reality that can go both ways obviously if people come

In complaining about certain adverse events even though they might be having a good clinical response we have to take that into consideration in ultimately defining whether that therapy is useful or not for that specific person alright well thank you so much roger thank you thanks a lot time this podcast represents the copyrighted content of the american headache

Society will use expressed in this podcast represent the opinions of the participants it does not necessarily reflect the views of the american headache society to find out more about the american headache society in its journal headache please visit wwe

Transcribed from video
A Comparison of OnabotulinumtoxinA and Topiramate for the Treatment of Chronic Migraine By Wiley