Bridging the Gap: Sustained Treatment Effect of Glabellar Lines With Twice-A-Year Treatment With DaxibotulinumtoxinA

Abstract

BACKGROUND

To achieve natural-looking outcomes when treating dynamic lines with botulinum toxin (BoNT), retreatment must be timed such that the patient maintains a relatively constant aesthetic outcome. Although first-generation BoNT products require retreatment with 3- to 4-month frequency to avoid discontinuous correction, the average patient returns for treatment every 6 months, when these toxins have generally fully worn off.

OBJECTIVE

To discuss the number of days a typical patient treated with daxibotulinumtoxinA for injection (DAXI) or legacy BoNT products will spend undertreated or uncorrected in a given calendar year.

MATERIALS AND METHODS

Median time for maintaining glabellar lines in the “none” or “mild” severity range was compared for approved doses of onabotulinumtoxinA (ONA; 120 days) and DAXI (168 days).

RESULTS

The average patient treated with 40U of DAXI every 6 months can expect to be uncorrected (with “moderate” or “severe” glabellar lines) for 14.5 days between visits compared with 61.5 days for 20U of ONA.

CONCLUSION

An extended duration BoNT product can be expected to create greater consistency in aesthetic outcome and minimize the discontinuous correction commonly seen with first-generation BoNT products for patients treated twice a year, without requiring a change in patient behavior regarding visit frequency.

The successful treatment of dynamic facial lines with botulinum toxin (BoNT) is achieved by reducing the strength of facial musculature. This effect typically peaks at 2 to 4 weeks after treatment, whereupon the pharmacology of the toxin dictates a progressive decline in efficacy. Without retreatment, the toxin's effect wanes until the wrinkle severity returns to baseline. Retreatment halts this decline and restores the desired effect. The timing of retreatment is a balancing act between the desire to maintain a relatively constant aesthetic outcome and the cost and feasibility of frequent treatments. Preventing periodic return to baseline severity between treatments spares the patient from a discontinuous correction, which could also be described as a “peak and valley” effect (Figure 1A,B), and is an important aspect of creating consistency in appearance reflective of a natural aesthetic. However, in clinical practice, it is estimated that an average patient returns for 1.85 treatments per year (based on data from 690,513 patients across 782 aesthetic practices) rather than the 3- to 4-month frequency necessary to prevent discontinuous correction.¹ Whether this reduced frequency and increased interval is due to cost, convenience, or disconnect between the patient's dynamic line severity and their perception of severity as the treatment effect gradually declines, its consequence is that the typical patient treated with legacy BoNT products will spend a substantial portion of a given calendar year undertreated. An average patient retreated every 6 months with these toxins will generally experience a full wearing off of the neuromodulator's efficacy and a return to baseline wrinkle severity, a highly undesirable outcome.

Figure 1.

Treatment twice per year with DAXI (A) versus ONA (B) and associated time with suboptimal correction (red shaded area). Note that for ONA, all of the subjects have lost correction resulting in “none” or “mild” severity lines at approximately 5 months. From this time point until retreatment, the patient is “uncorrected.” These data are translated into a visual aid conceptualizing the correction gap for patients (C) with associated time spent with suboptimal correction (gray) and uncorrected (red, ONA only). DAXI, daxibotulinumtoxinA for injection; ONA, onabotulinumtoxinA.

A BoNT product with a longer duration would eliminate or attenuate these gaps in aesthetic outcome with no change to a patient's current behavior. For neuromodulator treatment, the amount of time the average patient spends in an uncorrected state is a rarely discussed outcome, but one of central importance. As with most medications, repeat administration of BoNT should be timed to preserve an appropriate clinical effect and avoid the complete loss of efficacy between treatments. In clinical practice, patients are often advised that proactive management of dynamic lines, with regular treatment before the full return of movement, is essential to minimize the correction gap and consistently preserve improved appearance. For legacy toxins, dosing for most patients should be approximately every 3 months, in particular for those patients unlikely to tolerate discontinuous correction (e.g., patients with highly public lives or particular individuals), but can be extended to 4 months or beyond for some patients.

When reviewing clinical data to estimate the optimal time for retreatment, loss of “none” or “mild” severity is the most relevant study end point because it reflects the crossover point where patients return to moderate or severe lines and where they would most likely identify a need for retreatment. Furthermore, this measure is of relevance to clinical practice because it captures both those patients who wish to have a more natural outcome (i.e., mild) and those who wish to have a stronger effect (i.e., none). For daxibotulinumtoxinA for injection (DAXI [DAXXIFY; Revance, Nashville, TN]), the median duration of effect for maintaining glabellar lines in the “none” or “mild” severity range is 24 weeks (168 days).² Based on these data, the average patient treated with the approved 40U dose of DAXI every 6 months would expect to be uncorrected for a total of only 29 days in a given calendar year. The median duration of effect for maintaining “none” or “mild” severity for onabotulinumtoxinA (ONA) has been reported to be 120 days, suggesting that patients treated twice a year with 20U of ONA can expect to spend a total of 123 days with moderate or severe glabellar lines (Figure 1C).³

Patients seek BoNT-A treatment largely because they do not like the way that their dynamic lines make them feel about their appearance. It is therefore essential to not just treat to prevent the return of the glabellar lines, but also to protect the confidence and satisfaction that follows treatment. Ensuring that these treatment effects are persistent and beneficial for patients for as many days as possible is central to any aesthetic practice. By closing the correction gap left by first-generation BoNT formulations, twice-a-year treatment with DAXI is able to give patients far more time in a corrected state and reduce discontinuity in appearance. Although timing of retreatment must be individualized for each patient and proactive management with more frequent DAXI injections may be ideal for some as they lose “none” or “mild” severity, the longer duration afforded by the DAXI formulation assures that patients will be happier for longer, even if they maintain the pattern of twice-yearly injections.

The publication of pivotal trial data showing that patients treated with DAXI can expect a median of 6 months of correction prompted studies attempting to show that extended duration could be achieved by using a “high dose” of legacy BoNT products. For these products, doubling or even quadrupling the on-label dose and injecting a more concentrated solution resulted in only a modest increment in duration but was unable to match the duration of effect of 40U of DAXI.^4,5 Although these data are informative, utilization of these higher doses is unlikely because the need to use more than twice as much product runs counter to their product label, risks increasing adverse event rates and the development of neutralizing antibodies, and may be cost-prohibitive for patients. Thus, in real-world practice, the standard of care with these legacy products will most likely remain the on-label doses. It should be noted that the approved doses for ONA (20U) and DAXI (40U) contain an identical amount of core BoNT-A (0.18 ng). The determination of unit potency is unique and proprietary for each product, and units are not comparable.⁶ The fact that 2 products with equal amounts of core neurotoxin perform differently demonstrates the impact of product formulation on clinical performance.

A product with extended duration will create greater consistency in aesthetic outcome for patients being treated twice a year. For patients, treatment with a product that has a 6-month duration fills an important unmet clinical need and allows them to experience a more continuous correction throughout the year, even without a change in behavior regarding visit frequency, by minimizing the discontinuous correction commonly seen with first-generation BoNT products.