The Pretty and the Gritty

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A patient asked me why her tox had stopped working. It hadn't. It was working exactly as well as it did the first time she had it, eight years earlier.

This episode is about what actually changes, why more units at shorter intervals is the wrong answer, and why true resistance is far rarer than people think.

Sources for this episode

Everything in this episode comes from a paper you can look up yourself.

• On how well it works, and for how long. Carruthers A, Carruthers J, et al. Two double-blind, randomised, multicentre trials of onabotulinumtoxinA for glabellar lines. Peak effect at 30 to 60 days, median duration around 120 days, more than 80 percent of participants satisfied at day 60. These trials were run and reported with the involvement of the manufacturer, which is worth knowing when you read them.
• On resistance and neutralising antibodies. Naumann M, et al. Meta-analysis of neutralising antibody formation across the onabotulinumtoxinA registration trials. Thirty-three trials, nearly six thousand participants. In the glabellar line group, three people out of eight hundred and ten. In the crow's feet group, none out of nine hundred and fifteen. In chronic migraine, at roughly ten times the cosmetic dose, none out of five hundred and one.
• On whether antibodies actually predict non-response. Dover JS, et al. 2018. Of the participants who genuinely stopped responding, around half had no detectable neutralising antibodies at all, and of those who did develop antibodies, most continued to respond.
• On why older studies report much higher rates. The product was reformulated in 1997. The original formulation carried roughly five times more neurotoxin protein per 100 units. Rates reported before that reformulation describe a different product.
• On the migraine comparison. The PREEMPT chronic migraine protocol uses 155 to 195 units across 31 injection sites in seven muscle areas, every twelve weeks. The average glabellar dose in the cosmetic trials was around seventeen units.