Dr. John H. Joseph discusses the true potential duration of botulinum toxin injections by increasing the dose and decreasing the volume of reconstitution.
John H. Joseph, MD, is a double board-certified plastic surgeon in Encino, California
“Darwin will tell you if you don’t evolve you die. And on some level, you have to evolve eventually to being able to customize [neurotoxin] volumes of reconstitution and doses for the indication to get the best result,” said John H. Joseph, MD, who presented “State of the Art Neurotoxins and a Paradigm Shift in Reconstitution” at Music City Scale 2022.
“About 15 years ago, I was involved in a clinical trial that allowed us to increase the dose of a toxin… to capture the results for men better because we knew that men have more muscle mass, so we were able to up the dose a little bit. What I also saw was, yes, they got a better aesthetic result, but the duration also extended.”
Despite pitching industry with these results to do further research, no one was interested, said Dr. Joseph.
“So I did the trial myself… [and] lo and behold, when I increased the dose, it increased the duration.”
This time, Galderma provided a grant to perform a multi-site trial to evaluate the duration of effect of one 120-unit abobotulinumtoxin dose to treat moderate to severe glabellar lines,1 said Dr. Joseph.
“The data showed… increasing the dose, increased the duration.”
But he was concerned that increasing the dose could also increase adverse events, he said.
“So I came up with this very simple conceptual algebraic equation that said the field of effect…is proportional to diffusion and spread… I figured if I increase the dose, maybe it’s wise I decrease the volume of reconstitution, so I can control that field of effect.”
According to Dr. Joseph, he decreased the reconstitution volume by 20% from compliance.
“And it worked. And adverse events [were] very low.”
Galderma opted not to pursue this clinical research further, but Allergan did, said Dr. Joseph.
Allergan performed a 48-week, double-blind study that compared 40 U, 60 U, and 80 U onabotulinumtoxinA vs 20 U and placebo.2
However, there were concerns about adverse events given the larger doses, said Dr. Joseph, who significantly lowered the volume of reconstitution, resulting in a volume for injection into the Glabella of only 0.25 mL as compared to 0.5 mL on label.
“…if you understand that little equation, I don’t think there will be more [adverse events]—I think there’ll be less because we’ve really focused [the field of effect]…and you can’t get an adverse event if the toxin doesn’t get to a place you don’t want it to go.”
In fact, the ptosis rate in this study was significantly lower than that in other neurotoxin studies using on-label dosing, said Dr. Joseph.
“So it looked like not only did it extend the duration (doubled it basically), but safely, with even a decrease [in adverse events].
Galderma and Merz each performed similar studies and achieved similar results, he said.
“So clearly we have for 30 odd years been underdosing and overdiluting botulinum toxin with respect to the true potential duration that’s there. We accepted three to four months, and that’s only halfway there.”
And if duration can be extended in the glabella, it should for the other facial muscles treated with botulinum toxin, said Dr. Joseph.
“We need to reboot and think about what is the optimal way to treat the face. Because if we know we can get 7 months plus or minus [in the glabella], we should be able to get it in the crow’s feet and other areas too. How do we go about doing that?”
Using a set universal reconstitution and dosing is not the best physicians can do, said Dr. Joseph.
“We have to customize the volume of reconstitution and dose for every indication in the face.”
It’s a hard sell, but the idea of a longer duration is generating some interest, said Dr. Joseph.
“This to me is the first significant change in our evolution of botulinum toxin injections in a long time….”
Financial Implications
For any practice that believes they may lose money by seeing their patients less often, it’s unlikely, said Dr. Joseph. The same concern was expressed when longer lasting fillers came out compared to Collagen. Obviously, this did not result in a decrease in revenue.
“Let’s look at a 10-year scenario with a patient. I’m going to treat you as my patient for 10 years… if I give you [20 units of Botox] every 4 months for 10 years, that’s 30 injections over 10 years. Okay? And that means you used 600 units. Now, if I give you 40 units every 7 months, that’s less than 18 injections (but I’ll call it 18) and that’s 720 units. So actually, you’ve injected 18% more toxin over 10 years. That’s number one. So you actually use more product. Number two is, you actually see the patient 40% less.”
Therefore, according to Dr. Joseph, practices come out ahead.
“…you are actually doing better because you are injecting more units with less patient interactions. So if you’re really into the bean counting of your practice, you’re making more money with less time; you’re working less and making more. That’s good. But more importantly everybody comes out a winner: the patient and the practice.”
References
- Joseph JH, Eaton LL, Robinson J, Pontius A, Williams EF III. Does Increasing the Dose of Abobotulinumtoxina Impact the Duration of Effectiveness for the Treatment of Moderate to Severe Glabellar Lines? J Drugs Dermatol. 2016 Dec 1;15(12):1544-1549. PMID: 29106437.
- Joseph JH, Maas C, Palm MD, Lain E, Glaser DA, Bruce S, Yoelin S, Cox SE, Fagien S, Sangha S, Maltman J, Lei X, Brin MF. Safety, Pharmacodynamic Response, and Treatment Satisfaction With OnabotulinumtoxinA 40 U, 60 U, and 80 U in Subjects With Moderate to Severe Dynamic Glabellar Lines. Aesthet Surg J. 2022 Jun 15:sjac157. doi: 10.1093/asj/sjac157. Epub ahead of print. PMID: 35704394.
Disclosure: Dr. Joseph is an advisor and has conducted clinical trials for Galderma, Allergan, Merz, Revance, Hugel, Croma, and Evolus.