Imagine if you could get Botox on the PBS!! Expressions would start disappearing off faces all around you, turning Australia into a society of strangely youthful but surprised-looking middle-aged people.
In fact, the treatment with perhaps the most wildly successful brand name in medical history has hopefully begun to turn a corner towards a newfound and deserving respectability. It has been listed as of March 1st for the treatment of chronic migraines, ie people who have true migraine headaches more than half of the days in a month, but are essentially normal on the days without a headache.
I’ve written previously about the massive, invisible public health toll of migraine. As it happens, for the last few years I’ve also done a secretive sideline in injecting Botox off-label to treat migraines. I rabbit on about the importance of evidence and plausibility in choosing treatments, so let’s have a look at how my practice came to be so far ahead of PBS-approved methods.
The idea of using botulinum toxin in medicine goes right back to a German physician/poet (where are they all now?) Justinus Kerner in 1822. Kerner correctly identified the responsible toxic substance causing an outbreak of paralysis in villagers who got stuck into a batch of dodgy sausages. Rather prosaically for a poet, he christened the new toxin wurstgift or ‘sausage poison’. He went on to speculate that it could be helpful to treat conditions caused by muscle overactivity. It only took another 100 years or so to isolate the protein of the toxin, and another 60 or so after that to purify and manufacture the toxin in a formulation fit for clinical use.
I began learning about botulinum toxin as a registrar working in a training job looking after people who had suffered acquired brain injuries. My boss in that job had pioneered the use of the toxin to help improve the rehabilitation of ABI survivors who had high muscle tone which was impairing their walking. In this setting, the principle is similar to that of children with cerebral palsy. The toxin selectively weakens very overactive muscles to enable a proper balance of forces around a joint and therefore normal movement patterns to be learned by the brain. In cosmetic use, the toxin is placed in muscles which contract to produce crow’s feet, laugh lines and other such stigmata of a lived-in face.
Its use in migraine arose from some chance observations and feedback from patients having it for cosmetic purposes during the mid 1990s. Open-label studies such as this one soon followed. This was about when I began following the literature on botulinum toxin and headaches. The positive outcomes in open-label studies led on to RCTs like this one some of which had results that were contradictory and required a lot of interpretation. The definitive research program, which was designed and powered to demonstrate efficacy using the lessons from previous studies, was the PRE-EMPT group of studies.
The acceptance of Botox onto the PBS was after careful consideration of the burden of disease, public health consequences, the need for safer, less toxic migraine prophylaxis and the weight of high-quality evidence from over a decade of serious research. When the toxin works well, it at least halves the number of severe headaches. It doesn’t look that good in unselected migraine patients, which is why the early studies were so mixed. If you only have infrequent migraines, you don’t see any benefit. In a big study, spectacular results for one in ten patients look unimpressive if all the rest in the treatment arm don’t improve. The early RCTs were analysed to try to identify who the toxin responders might be. That was why the PRE-EMPT studies were compelling. They set out a patient selection and treatment protocol that would give clear clinical guidelines for who should benefit, and demonstrated a clear positive outcome in responders. Importantly, if they had been negative, there would be tears from Allergan shareholders and management but the push to promote it as a migraine treatment would have stopped right there.
Although the cost of the treatment won’t be cheap (around $700 every 3 months if you use the PRE-EMPT protocols) that is more than offset by saving the migraineur a single trip to hospital during that time.For one of my patients, it has reduced her number of headaches from 25 days out of 30 to a couple per month, and allowed her to stop her other migraine drugs and get back to part-time work. Another way to look at the cost equation is to add up the number of triptan drugs saved by effective prophylaxis. The cheapest triptan still costs around $5 a tablet, and anything up to 4 of these will be used in a bad migraine. The newer triptans run to $13-15 a tablet. And how do you cost the achievement of changing a migraineur from a disability pensioner to a working taxpayer? Pretty good value for a couple of grand a year. You could change the lives of half a dozen migraine sufferers for the cost of a single Parliamentary bookcase!
The taming of Botulinum toxin represents a triumph of both science and technology, since at various times one has had to wait for the other to catch up in order for humanity to benefit from this most potent of naturally occurring bacterial proteins. I’ve been using botulinum toxin (Botox and Dysport brands) for selected ‘difficult’ pain patients for around 7 years, and was pleasantly surprised to see it get approved for PBS listing in migraine. I knew the PRE-EMPT studies were convincing, and I certainly knew the effect that the toxin can produce in practice, but I’m used to seeing effective treatments get held up for one reason or another. I’m glad for migraine sufferers in Australia that the PBAC was able to see past the lingering perception of botulinum toxin as a frivolous drug used for trivial purposes. Fewer headaches for patients, the health system and taxpayers will be the result.