New Frontiers in Neurotoxins

Neurotoxins first received an aesthetic indication in the US a decade ago, although in reality they have been used for over two decades by a large portion of cosmetic surgeons. During the past 10 years, onabotulinumtoxinA (Botox Cosmetic, Allergan) has been approved for new indications, which has given physicians more flexibility to explore and apply the unique characteristics of neurotoxins. In the same time period, we've also seen the addition of another neurotoxin, abobotulinumtoxinA (Dysport, Medicis), which offers a unique set of benefits and further enhances cosmetic surgeons' abilities to achieve a nuanced effect with facial aesthetic procedures. Most recently, incobotulinumtoxinA (Xeomin, Merz) has been approved. These advancements, while certainly momentous, represent only the tip of the iceberg regarding the potential of neurotoxins and the ways in which cosmetic practitioners can harness them in practice. Coming years will likely bring a myriad of new advancements in the use and technique of these agents, and the probability for the approval of more neurotoxins for aesthetic indications. Refinements in technique as well as new indications are most likely responsible for some of the recent surge in use and patient interest, with uses like crow's feet and forehead wrinkles being quite popular despite not being an FDA-approved indication.

At the 2011 Cosmetic Surgery Forum in Las Vegas this past December, several panelists and attendees weighed in on the current state of neurotoxins. This article explores the unique benefits of neurotoxins, the conversation/discussion among the panelists and audience (a key distinguishing factor of Cosmetic Surgery Forum), important considerations in the use of neurotoxins, and the future in this arena.

The Current Outlook

Botox has had a market share in the neurotoxin realm for some time, but the recent addition of Dysport and the approval of Xeomin give physicians a unique opportunity to weigh the individual characteristics of each agent and understand the subtle ways each works. According to Heidi Waldorf, MD, the decision of which toxin to use, as well as when and where, hinges on four characteristics: profile, patient, protein, and price.

Regarding the profile, it is important to look at the reconstitution and dosing of each agent. For reconstitution, Dr. Waldorf notes that bacteriostatic saline is associated with less pain. However, questions remain as to whether bacteriostatic saline really offers protection against contamination, and whether benzyl alcohol contained in the preparation reduces toxin potency over time.

In terms of dosing, Dr. Waldorf observes that, in general, 1-5cc per 100 units is acceptable for both Botox and Xeomin, while 1.5-3cc per 300 units would be the range for Dysport. More specifically, 2.5U/0.05cc is the ideal dosage for Botox and Xeomin, and 5U/0.05cc is ideal for Dysport. As for dosing ranges, Dr. Waldorf observes that 15-25 units of Botox is acceptable for the glabella, while for crow's feet 10 units per side is preferable. For the DAO (depressor anguli oris), she recommends 3.5 units on each side, five units for the mentalis, and 20-40 units for each side in the mandible.

Regarding Xeomin, Cheyl Burgess, MD observes that it is available in 50 and 100 unit vials, has an FDA standard reconstitution dilution of 2.5mL normal saline, and has the same boxed warning as other neurotoxins. Clinical results with the two agents (Botox and Xeomin) also appear to be similar in certain head-to-head studies, notes Dr. Burgess. For example, Sattler G, Callander M, Grablowits D, et al. examined 381 subjects who received 24 units, a non-standard dosing, of either incobotulinumtoxinA or onabotulinumtoxinA (3:1), in a randomized fashion and observed responses over 12 weeks. Four weeks after injection, both neurotoxins were deemed to be effective (incobotulinumtoxinA: 96.4%, onabotulinumtoxinA: 95.7%). Another study compared Botox and Xeomin in the treatment of crow's feet. Twenty-one patients with facial wrinkle scale (FWS) of 2-3, received 12 units, split-face, to crow's feet with a reconstitution ratio of 1:1. After four months, both sides still showed good efficacy.

More studies are needed to see if Xeomin is equivalent to Botox with regards to efficacy. However, it is worth noting that these studies can obscure the subtler differences between the agents, which can only be determined with more use and experience. Perhaps the most significant difference between the two agents from a clinical standpoint, Dr. Burgess notes, is that Botox contains complexing proteins while Xeomin does not. Dr. Waldorf observes that Xeomin is often referred to as the “naked toxin” for this reason. Dr. Burgess suggests that because of the lack of proteins, Xeomin may be efficacious for patients who fail to respond to Botox.

Dr. Schlessinger's Tip: At this time, I generally divide these agents into age groups, with Dysport being favored by my patients in the 20-45 age range, Botox for the 40-60 age range, and Xeomin for the 55 and upward range due to its lighter touch. For many patients, it is worthwhile to try newer treatments such as Dysport and Xeomin to see which one they like the best and for a new experience.

Costs and Other Considerations

Undoubtedly, the most noteworthy difference between Botox and Xeomin for patients is the cost. Dr. Burgess observes that while Botox averages $525 per 100 units, Xeomin averages roughly $425 or less per 100 units. Therefore, for patients who want to try Botox but are wary about costs, Xeomin may present a more cost-efficient option, Dr. Burgess notes. Xeomin can also help keep costs down for physicians new to practice or physicians introducing neurotoxins. But Corey Maas, MD points out that this is likely to create some dilemmas for physicians, as patients will be aware of price points.

When it comes to price, Dr. Waldorf observes that she treats by anatomical unit rather than unit of drug. The patient is not just paying for the product, but also for the physician's time and expertise, Dr. Waldorf explains. Therefore, she recommends having a very clear discussion with the patient about what it is they seek from treatment and what agent will best suit their expectations. Dr. Waldorf further notes that, when considering price, it is always important to consider the type of patient you are serving, as well. This is important not just from patient to patient, but also in terms of where you practice. For some practices, it will make more sense to treat by area, whereas others are better off treating by unit. Dr. Waldorf continues that while clinicians should do what their patients want, they should also teach them and guide their perceptions regarding cost and information about the different products. Clinicians should make a decision based on what makes sense both for them and the population they serve.

Dr. Schlessinger's Tip: It is great to have options out there that allow us to offer discounts, rebates, and other promotions to new and existing patients. Without the entry of Dysport and Xeomin, we wouldn't have seen these, so we owe them a debt. There is no harm in introducing patients to new and less expensive alternatives, as it may result in the ability for them to do other treatments at the time, such as laser or fillers. Additionally, the goodwill of assisting patients to maximize value is always appreciated.

Loking to the Future

The addition of more neurotoxins to the market will benefit patients and physicians, but clinicians should be cognizant of the impact these additional agents will have on their practice. This is true not only for neurotoxins, but for the expanding aesthetic market more broadly. In time, we will see a number of new procedures, products, and techniques that will change how we practice aesthetics. Some of these potential developments are indeed exciting, such as the targeting of multiple tissue planes with ultrasound therapy (Ultherapy) and perhaps even topical neurotoxins that are currently in development. It may not always be easy to navigate the changing terrain, but aesthetic clinicians would benefit from a view that many of these procedures are complementary. As Dr. Waldorf notes, physicians would not be wise to use just one toxin or just one type of filler. Instead, the physician is charged with making a choice based on understanding the nuances of each platform and each product within that platform. Regarding toxins specifically, the last 10 years have taught us that as we continually learn about these agents, we will discover new and exciting ways to harness them. Given the advancements made thus far, Dr. Waldorf notes that neurotoxins are no longer about paralysis, but instead about reshaping.

The future is truly much more interesting with competition leading great companies to innovate. Their innovations, coupled with the ingenuity of dermatologists and cosmetic surgeons, will result in more procedures that appeal to our patients and better outcomes.

Dr. Schlessinger is an advisory board/consultant, researcher, or stockholder with Allergan, Stiefel/GSK, Galderma, Obagi, Ortho Pharma (Johnson & Johnson), Medicis, and Revance. He is also President of FixMySkin, which recently introduced the 1% Hydrocortisone FixMySkin balm line.

Joel Schlessinger, MD is Founder and Course Director of Cosmetic Surgery Forum. He practices in Omaha, NE. The 2012 Cosmetic Surgery Forum will be held from Nov. 29 – Dec. 1 at the Venetian/ Palazzo in Las Vegas, NV. For more information and to register, visit www.CosmeticSurgeryForum.com