CME: Re-examining the Optimal Use of Neuromodulators and the Changing Landscape: A Consensus Panel Update

April 2020 | Volume 19 | Issue 4 | Supplement Individual Articles | 35 | Copyright © April 2020

Published online March 20, 2020

Michael S. Kaminer , Sue Ellen Cox , Steven Fagien , Joely Kaufman , Mary P. Lupo , Ava Shamban

aDepartment of Dermatology, Yale School of Medicine, New Haven, CT bDepartment of Dermatology, Brown Medical School, Providence, RI cSkin Care Physicians, Inc, Chestnut Hill, MA dAesthetic Solutions PA, Chapel Hill, NC eSteven Fagien MD, Boca Raton, FL fSkin Associates of South Florida/Skin Research Institute, Coral Gables, FL gLupo Center for Aesthetic and General Dermatology, New Orleans, LA hAVA MD, SKIN FIVE, Los Angeles, CA

is formulated differently, has a different manufacturing process, and demonstrates unique characteristics.19 They vary in terms of composition, weight, chemical properties, and biologic activities (Table 1),20-23 and subsequently are not exactly interchangeable.24,25 An awareness of the differences between agents, particularly related to dosing and reconstitution, is critical.26 Although each of the 4 BoNT-As can be used with comparable effect and duration and are quite similar in the opinion of the consensus group, the specific results obtained with each agent vary in practice and become more apparent as clinicians gain more expertise.

The panelists suggested that how the drug gets to the muscle may be different with the various agents, influencing the field of effect (spread), and the results, in some areas. However, the size of the field of effect, which helps prevent skip areas, is difficult to measure, and comparisons between preparations have yielded equivocal results.27 In some areas, like the crows, feet, it is essential. In the experience of the group, the 4 BoNT-As fall on a spectrum with regard to field of effect. OnabotulinumtoxinA (Botox®, Allergan Inc.), the first approved agent, became the gold standard. AbobotulinumtoxinA (Dysport®, Galderma Laboratories, L.P.) appears to have a wider field of effect, and incobotulinumtoxinA (Xeomin®, Merz Pharmaceuticals GmbH) seems to have a narrower field of effect. The latest approved agent, prabotulinumtoxinA-xvfs, has a tight, precise field of effect. When using agents with a narrower field of effect, neighboring muscles may not be affected, requiring a change in strategy. This can be compensated for by increasing the dilution or by adding a few more injection points so they are closer together.

The panelists clarified that increased diffusion or field of effect is not necessarily a detriment unless BoNT-A is being injected midpupillary right on the brow, or periorally. Clinicians should understand how much each agent diffuses, and then determine how to best use that to an advantage based on the muscles being injected. Similar to soft tissue fillers, the 4 BoNT-As each function differently and aesthetic physicians need to know their nuances to get the best results.

Certain BoNT-As may work better than others in different areas of the face. According to the group, some patients may get profound results with a specific BoNT-A, and others not as much. That demonstrates how recruitment makes a big difference in some areas, and in some patients. In their initial experience, for example, some panelists believe prabotulinumtoxinA-xvfs provides “smoother” results than other BoNTs-As in select areas of the face. Similarly, several panelists felt that abobotulinumtoxinA provides a wider field of effect, which can be useful in areas such as the forehead and crow’s feet. The group agreed that because of these nuances, it makes sense for injectors to get experience with all 4 agents rather than sticking with just 1 agent they may have become comfortable using. A few patients may benefit from treatment with several BoNT-As because they work a little differently.

The panel agreed that for aesthetic physicians to perform at an expert level, they need to understand how all the BoNT-As work as well as nuances of varying dilution and dosing and how they affect clinical results. The volume of saline depends on the concentration the clinician wishes to obtain from each vial.26 The concentration can be adjusted to limit or increase the diffusion when treating localized or broad areas, respectively. Care must be taken, and concentration considered, however, when attempting highly selective facial muscle weakening. For onabotulinumtoxinA, prabotulinumtoxinA-xvfs, and incobotulinumtoxinA, most panelists reconstitute with 2 to 2.5 mL of saline per 100-U vial, although several use as much as 5 mL per 100-U vial. For abobotulinumtoxinA, the corresponding reconstitution is generally between 1.5 and 6 mL per 300-U vial. For example, some panelists use a 1.5 mL dilution of abobotulinumtoxinA in the glabella to increase precision and use a 6-mL dilution elsewhere in the face. The group generally agreed that using a higher dilution of prabotulinumtoxinA-xvfs in the forehead would increase its diffusion, making it behave more like onabotulinumtoxinA or abobotulinumtoxinA, likely because of the agent characteristics and baseline patient anatomy.

BoNT-As each have different personalities, just like fillers. Expert clinicians have learned how to use multiple fillers and understand how one filler may be better in a specific area than another. The introduction of a new neurotoxins should help aesthetic clinicians adjust their clinical practices, providing opportunities for growth. The consensus panel noted that new agents must be treated as unique. As clinicians use new agents, they need to re-evaluate their techniques for the other agents and the results they are getting, and then adjust their practices as part of the ongoing learning process. The group generally felt that starting dosages for the latest agent, prabotulinumtoxinA-xvfs, should be the same as for onabotulinumtoxinA, or maybe 10% more, depending on the area being treated. It was recommended that clinicians start using prabotulinumtoxinA-xvfs just like onabotulinumtoxinA—the same reconstitution and the same injections technique—until they are able to gauge its nuances. For incobotulinumtoxinA, the number of units is usually increased by 20% to 30%. AbobotulinumtoxinA is injected similarly but requires a different dosage calculation of about 2.5:1 to onabotulinumtoxinA.

The panelists agreed that the adverse events and safety profiles of the 4 agents seem to be the same. They believe that adverse events, when they occur, are often the result of substandard technique and training. The major tools for preventing adverse effects from BoNT-A are knowledge and skill, especially proper techniques of dilution, storage, and injection, as well as the