What does the future hold for aesthetics? The 4 four available neuromodulators share a similar mechanism of action and efficacy profiles, but they each have their own unique characteristics, and now an emerging agent is about to enter the scene. Dr. Joel Cohen and Dr. Carolyn Jacob discuss the subtle differences among neuromodulators and the importance of dosing for duration, specifically for the glabella and upper face. They also explore potential adverse events and strategies to minimize your patients’ risks.
Neuromodulator Dosing for Duration
Neuromodulator Dosing for Duration
Welcome to CME on ReachMD. This activity, entitled “Neuromodulator Dosing for Duration,” is provided by Prova Education and is supported by an independent educational grant from Galderma. Before starting this activity, please be sure to review the disclosure statements as well as the Learning Objectives.
Here’s Dr. Joel Cohen
Despite sharing a similar mechanism of action and efficacy profiles, in some cases, there are 4 different currently available neuromodulators on the market. I’m Joel Cohen from Denver, Colorado. I’m a board-certified, fellowship-trained dermatologist, and I’m excited to be with Dr. Carolyn Jacob from Chicago, who’s also a board-certified, fellowship-trained aesthetic dermatologist. Carrie, thank you very much for joining us.
So, let’s dive right in. Dr. Jacob, can you give us an overview of the currently available botulinum toxin products that we have available in our practices?
Thanks for having me, Joel. Yes, so it’s a really exciting time to be a dermatologist. Those of us who’ve been practicing for a while remember the off-label-use days when all we had was onabotulinum toxin, but now we have abo, we have ona, we have inco, and we have prabotulinumtoxin. And hopefully coming up later this year, we’ll talk about in a minute, daxibotulinumtoxin. So, there’s 4 on the market in the United States currently, and we use them all in our office because I kind of look at it as people liking Coke versus Pepsi versus any of the other colas. People kind of have their favorites from their experiences. How about you, Joel?
So we’ve actually done the clinical trials, as you have, on all 4 products, and sometimes patients ask for a specific product, perhaps if they were in the clinical trial or they know somebody who’s had a good experience with the product in the past, such as a friend or a sister. But there are main products that we carry in the office that seem to be, certainly, a bit more popular. People who have that name recognition with Botox, and Dysport is really popular in our practice, as well, and represents about half of all patients who get treated with neuromodulators in our practice.
I agree, and there are some subtle differences between these 4 products that we have available. Even though they all have the same 150 kilodalton molecule, they have different epitopes on them, so people seem to have a little bit different experiences with them. One of the things that I find interesting, and when I’m explaining it to a new patient who’s coming in to see us, is the fact that we do have those clinical trials showing that abobotulinum toxin sets in in about 1 to 5 days, and its duration in those clinical trials was also slightly longer than those of onabotulinum toxin. I also extract that, too, we have some off-label uses that we use these toxins for, one of which is the treatment of hyperhidrosis. And in those studies with abobotulinum toxin, the duration was about 30 days longer than that of onabotulinum toxin. So I usually have those conversations with patients if they are a brand-new patient trying to decide, again, what product they want to choose.
But we do find that all of them are effective. I’ve used all of them on myself because, of course, when we get something new, we want to see for ourselves how it works, and I find that patients are very satisfied with their treatments. There’s a few differences in terms of the FDA approvals, of course, of these different neuromodulators, as I like to call them. Whereas onabotulinum toxin is approved for the lateral canthal lines as well as the glabella, the other products are currently approved for the treatment of the glabella.
So with onabotulinum toxin specifically having upper face indications – glabella, crow’s-feet, as well as forehead – you know, that’s something where I think people are aware that you can use these neuromodulators in many different areas. And with ona actually having those 3 indications, do you think that that’s a barrier for people who may be interested in some of the other neuromodulators and think about FDA indications?
So the nice thing is, as dermatologists, we are allowed to use our clinical judgments to use different products off label, as long as we know that they’re safe and effective. And because you and I have been doing this for so long with so many of the products, we do know that all of them are safe and effective for the on-label areas, as well as other off-label areas. Because I know you are a master at this and I’m sure you, like we do, treat the platysma muscles and the depressor anguli oris and the masseters for narrowing of the face. So there’s a lot of areas that we constantly are using these neuromodulators for in a safe way for our patients. So I think that we, as practitioners, have the confidence in using all of the neuromodulators in different areas.
So, for people who may be interested in transitioning a patient from one neuromodulator to another, can you talk to us a little bit about that conversation and how you position things?
Yeah, and it’s interesting because, again, after doing this for over 20 years, I do find that some people feel suddenly the product that they were using doesn’t last as long, and there’s a lot of myths out there that say, oh, if you use it longer, it’s supposed to last longer, or your muscles will get more weak and your duration will be extended. And a lot of times, people just want a change, and so they’re interested in seeing if something else will be better. And a lot of times, we are switching between either abo to ona or ona to abo because those are the ones we most commonly use in the office, too. However, I do have some people where we’ve moved on to a third or a fourth just to give it a try. And again, there’s these slight differences in the patient’s responses to the neuromodulators that I think are unique and individual. And I don’t think that we’ve yet figured it out exactly why some people do better with one product versus another. And so that might be some very interesting area of research for the future, as well.
One of the other things that I’d like to note is that because we do have these indications for the forehead lines and lateral canthal lines, and the fact that I’ve been doing this since 1999 to people, our ways of treating patients have really changed. So back in the day, we were trying to load them up with neuromodulator to freeze everything and make sure nothing moved. And we’ve kind of come full circle now, where with our patients, they want to look more natural; they just don’t want to get deep creases. So we do a lot of prevention or pre-juvenation for patients who don’t want to get the wrinkles to begin with. But then other patients want to still have movement, just not get deep creases. So I find, at least in my practice, that I’m using much lighter doses on the forehead and sometimes a little heavier doses on the lateral canthal lines just because of the way the musculature acts for the patients.
So in terms of that, there is really the reality of combination therapy. We all use many different products in our practices in terms of giving patients a great overall aesthetic effect, and everybody wants to focus on, really, a natural look. And I agree with you, the forehead is an area that even though the FDA study that I participated in for onabotulinum toxin was 20 units, specifically, it’s very common for me to use 4 or 5 units in these micro aliquot dosing, where I oftentimes reconstitute it higher just to really pepper the forehead and sort of have these little areas of softening the musculature.
You know, I think that incorporating resurfacing into practice is important, as well, whether it’s non-ablative or ablative, and I think that we can help with that pre-juvenation, as well, especially with non-ablative. And then when people do have etched lines, using a combination of ablative fractional resurfacing and full-field resurfacing can really give people a nice improvement.
So can you talk to us about you’re technique for combination therapy and optimizing effect using neuromodulator plus filler, using neuromodulator plus laser resurfacing?
Sure. So we really like to look at the patient as a whole and decide what lines are there because of muscle movement, obviously, and then what lines might be etched in or there because of volume loss, and so a lot of times, we are doing both, using a neuromodulator and a filler on the same day. And I have absolutely no problem with doing both in similar areas. The one thing that we often try to avoid is when we’re doing a laser resurfacing of some type. I like to get that neuromodulator in two weeks prior to the actual laser treatment. That way, the muscles are relaxed, and they’re not going to crease over the newly treated skin because we really want that collagen to grow and not have an opportunity to re-crease, especially if you’re talking about the forehead. I also do love your description of peppering across the forehead. I call it sprinkling, but I’ll do the exact same thing, where I will take a very small amount of neuromodulator and put little, tiny bits across the forehead to soften the look without preventing the movement.
And one of the other interesting things, when we were talking back about pre-juvenation, is that we’ve got these younger patients who are looking at themselves in Zoom, and they want to make sure that they don’t get these lines or they’re just starting to see lines. And an interesting study that we both just participated in showed that patients who were given 50 units of abobotulinum toxin to the glabella had really great satisfaction, like 95% or more satisfaction, and having that treatment done just every 6 months. So it’ll be really interesting to see kind of what evolves in the future here, knowing that daxibotulinumtoxin, which is a little bit different neuromodulator because it has a carrier molecule attached to it to potentiate its effect, and its clinical trials were showing efficacy up to 6 months, whereas the other neuromodulator clinical trials were showing about 3 to 4 months. So it’ll be interesting to see how many of our patients we transition to something that we know lasts 6 months because of potentiating carrier molecule as opposed to some of these pre-juvenation people that are already satisfied with treatments just every 6 months. It’s really interesting.
For those just tuning in, you’re listening to CME on ReachMD. I’m talking to Dr. Carolyn Jacob from Chicago. I’m Joel Cohen from Denver, Colorado, and we’re really overviewing botulinum toxin agents and talking about dosing and duration.
So let’s talk a little bit about duration. There’s different ways to look at duration. Typically, when we think of duration for FDA studies at this point, we talk about a 2-grade improvement, for instance somebody who has severe muscles at animation or moderate muscles at animation dropping down 2 grades of basically animation to either mild or none. So if we look back at the original data from the Dysport FDA trial, I was in that trial and there were about 34% of patients in one study and about 44% of patients in another study that still had a 1-grade improvement at 5 months. So they may have gone from severe to moderate and/or from moderate to mild at that point at 5 months. So they’ve sort of crept back up, but they still had satisfaction with that. So that’s really based, you know, the basis of the DREAM study where, really, you and I and the other investigators in the study looked at efficacy over the course of 6 months and saw that patients had, as you indicated, a very high satisfaction, 95% satisfaction, when they’re dosed in the glabella every 6 months.
So, I think it’s important to point out to people that not everybody wants to actually have their muscle recapitulate, which can re-imprint those lines. There are some people that’ll be perfectly happy continuing on their usual use of abobotulinum toxin every 3 or 4 months to prevent that musculature. Maybe we’ll drop down in dose if people really stay on that. But there’s other people who, for one reason or another, whether it’s the finances or the convenience of coming in the office, may actually want to space things out to 6 months. And we know from ASPIRE data and the patient loyalty programs, that on the average, when it comes to the glabella, patients can come in, really, on average 1.9 times a year. So that’s really meant to simulate real-life experience in the DREAM study.
So how do you talk to patients about, you know, the fact that we do these studies, for instance, in the glabella, but it doesn’t necessarily extrapolate to other areas like the crow’s-feet or the forehead, and we still may want to see them come in more frequently because these are, oftentimes, more mechanical muscle groups?
Absolutely, and I think what I always tell patients to begin with, if there’s somebody younger who doesn’t have those etched-in lines, I tell them they’re going to start noticing the movement again, and that’s the time to come back in. But for them, that might not be until 4 or 5 months, and they don’t have those etched-in lines as the cue to start getting worse to have them come back in. But that’s really great for them because, again, they may be able to stretch this out a little bit longer. For patients with etched-in lines, they’re going to be more of your regulars; they really need to come in every 3 to 4 months. We want that collagen to build back up again into those lines to help to smoothen it out. And it is amazing, after doing this, again, since 1999, I’ve seen patients who had etched-in lines to begin with who no longer have them. And I agree with you. I think people with stronger muscles are going to want to come in on those more regular times.
However, like you mentioned, when we’re doing different dosing, or off-label dosing for the forehead – for instance, if I’m doing a little sprinkle to the forehead and it’s a lighter dose, it’s going to wear off faster. It’s a bigger muscle mass, but I intended for them to still have some movement, but unfortunately that also means that they may notice that movement faster than another area. So you may have people – sometimes we have people that come in one time for the glabella and the next time for their forehead, and they’ll kind of alternate it or add on as needed. So I really think there’s a lot of individuality about this for patients, and each time we visit with them, we take new pictures, we take a look at their movement, and we determine their needs for that day.
Carrie, we mentioned some of the combination treatments that we often do, whether it’s laser or fillers. Can you talk to us specifically about potential adverse events as far as some pitfalls that we should be aware of?
So the one main thing I see all the time is someone doing too much treatment to the forehead and dropping a female’s brows. This is an adverse event. It’s not really a true side effect of the medication; it’s more a fault of the practitioner who they went to before me doing way too much and not assessing a woman’s appropriate brow positioning. And that’s the complaint I get the most. And from that drop of brow, they then get an overfolding of their upper eyelid, which then makes it difficult to put on makeup, to put on mascara, etc. Now luckily, we both know that all wears off. Sometimes people will get a little edema of the eyelids or of the lower eyelids in the malar area, and the good news is the eyelid droop, which is noted, but I don’t see it that often in my practice, is something that can be reversed with some eye drops called Iopidine [apraclonidine]. So the nice thing about neuromodulators is they are a very safe tool to use for the help of reducing facial lines.
Well, this has been a fantastic session, and I just want to give you, Carrie, the opportunity to give some takeaway messages to people listening.
Sure. So again, assessing the patient’s face and eyebrows and eyelids first is of utmost importance to make sure that you get the best results for that patient. Everyone is unique, so don’t do a cookie-cutter treatment on everyone. Use your art, and look at the muscle movement and decide the dosing based on that because, truly, everyone needs differing amounts, and it has to be very specific for them. And then, less is more. Again, you can add more later, if you need to. We do our touch-ups for free because if it’s the first time I’m treating you, you’re a new patient to me, I want to make sure I do it absolutely perfectly for you. But if I overdo it, there’s no going back. So, less is more. Do a little bit less than you might need to with the availability of giving them a touch-up if needed.
Carrie, I want to thank you for joining us for CME on ReachMD. It’s been a pleasure to talk to you today, and I look forward to talking to you again.
Thanks so much, Joel.
You have been listening to CME on ReachMD. This activity is provided by Prova Education and is supported by an independent educational grant from Galderma.
To receive your free CME credit, or to download this activity, go to ReachMD.com/Prova. Thank you for listening.
In accordance with the ACCME Standards for Commercial Support, Global Learning Collaborative (GLC) requires that individuals in a position to control the content of an educational activity disclose all relevant financial relationships with any commercial interest. GLC resolves all conflicts of interest to ensure independence, objectivity, balance, and scientific rigor in all its educational programs.
Joel L. Cohen, MD
Director, AboutSkin Dermatology & Research
Associate Clinical Professor, University of California Irvine
Greenwood Village, CO
Consulting Fees: Allergan, Elta, Galderma, Lutronic, PCA Skin, Revance, Revision, Sente
Contracted Research: Galderma, Lutronic, Merz, Pulse
Carolyn I. Jacob, MD, FAAD
Director, Chicago Cosmetic Surgery and Dermatology
Affiliate Clinical Instructor, Northwestern University Feinberg School of Medicine
Consulting Fees: BTL Aesthetis, Galderma
Speakers Bureau: BTL Aesthetis, Galderma, PCA Skin
Advisory Board: Gladerma
Contracted Research: BTL Aesthetics, Galderma
Stock Options: Alastin, Allergan
- Stephen Chavez has nothing to disclose.
- Libby Lurwick has nothing to disclose.
- Brian P. McDonough MD, FAAFP has nothing to disclose.
- Tricia O’Leary has nothing to disclose.
- Colleen Resnick has nothing to disclose.
After participating in this educational activity, participants should be better able to:
- Discern important differences in dosing, duration, and safety among available and emerging botulinum toxin products
- Demonstrate effective injection techniques for different anatomic locations to ensure optimal aesthetic outcomes and minimize the risk for adverse events, with a focus on the glabella and upper face
- Recognize aesthetic situations where higher doses of a botulinum toxin with an increased duration of effect may be indicated
This activity is designed to meet the educational needs of dermatologists, plastic surgeons, dermatology nurse practitioners, and dermatology physician assistants.
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Global Learning Collaborative designates this enduring material for a maximum of .25 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
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This activity is supported by an independent educational grant from Galderma.
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