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Efficacy, Safety, and Subject Satisfaction After AbobotulinumtoxinA Treatment of Upper Facial Lines

Hexsel, Doris MD*; Cartier, Hugues MD; Hedén, Per MD; Delmar, Henry MD§; Bergentz, Per MD; Camozzato, Fernanda MD*; Siega, Carolina BSc*; Skoglund, Cecilia PhD; Edwartz, Carolina PhD; Rees, Diane PhD; Kestemont, Philippe MD§

doi: 10.1097/DSS.0000000000001679
Original Article
Open

BACKGROUND Botulinum toxins are the treatment of choice for wrinkles in the upper third of the face.

OBJECTIVE The purpose of this study was to evaluate the efficacy, safety, and subject satisfaction of abobotulinumtoxinA (ABO) for treatment of upper facial lines.

MATERIALS AND METHODS Subjects aged 35 to 50 years with moderate-to-severe upper facial lines were included in this study. Subjects received a maximum of 125 s.U. ABO in at least 2 indications with optional touch-up after 2 weeks. Assessments included wrinkle severity, global aesthetic improvement, subject satisfaction, and adverse events (AEs) 1, 3, and 6 months after treatment.

RESULTS At Month 1, 100, 94, and 93% of subjects were responders in dynamic glabellar, lateral canthal, and forehead lines, respectively. All subjects were improved 1 month after treatment, and the majority of the subjects were still improved after 6 months. After treatment, most subjects were satisfied with the appearance of their face, felt better about themselves, and agreed that the treatment made them look the way they feel. Seven subjects (22%) had 8 ABO-related AEs (mild–moderate); headache was most commonly reported (9%).

CONCLUSION AbobotulinumtoxinA effectively treated upper facial lines, with high patient satisfaction. Treatment was generally well-tolerated.

*Brazilian Center for Studies in Dermatology, Porto Alegre, RS, Brazil;

Centre Medical Saint-Jean, Arras, France;

Akademikliniken, Stockholm, Sweden;

§MEDITI -Clinique Science et Beauté, Juan-les-Pins, France;

Galderma, Uppsala, Sweden;

Zenith Healthcare Communications Ltd, Chester, Cheshire, United Kingdom

Address correspondence and reprint requests to: Doris Hexsel, MD, Brazilian Center for Studies in Dermatology, Rua D. Pedro II 1592, 90550-141 Porto Alegre, RS, Brazil, or e-mail: doris@hexsel.com.br

Galderma funded the study and provided the study products.

Interim results from this study were previously presented as abstracts/posters at the International Master Course on Aging Science (IMCAS) Annual World Congress; January 26–29, 2017; Paris, France, and at the 15th Aesthetic and Anti-aging Medicine World Congress (AMWC); April 6–8, 2017; Monte Carlo, Monaco.

D. Hexsel is a consultant for Galderma and Merz. P. Hedén is a consultant for Allergan, Teoxane, and Galderma. C. Skoglund and C. Edwartz are employed by Galderma. D. Rees of Zenith Healthcare Communications Ltd., provided medical writing assistance, funded by Galderma. P. Kestemont is a consultant for Allergan, Filorga, Galderma, Teoxane, Universkin, and Vivacy. The remaining authors have indicated no significant interest with commercial supporters.

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Botulinum toxins have been used for more than 20 years in facial aesthetics and are the treatment of choice for dynamic wrinkles occurring in the upper third of the face.1 The treatment is well-tolerated and produces effective results, with high subject satisfaction.2–10

There are several commercially available botulinum toxins including but not limited to onabotulinumtoxinA (ONA) (Botox; Allergan, Inc., Irvine, CA), abobotulinumtoxinA (ABO) (Azzalure/Dysport; Ipsen Biopharm Limited, Slough, United Kingdom), and incobotulinumtoxinA (INCA) (Xeomin, Merz Pharmaceuticals GmbH, Frankfurt, Germany). AbobotulinumtoxinA was approved by the Food and Drug Administration in 2009. In Europe, ABO has been indicated since 2009 for the temporary improvement in the appearance of moderate-to-severe glabellar lines (GL). In November 2016, ABO was approved in the European Union for lateral canthal lines (LCL) through a decentralized procedure including 22 member states. It also has a marketing authorization in Brazil for the treatment of hyperfunctional facial lines and additional medical indications.

Although very rarely used in clinical practice, most publications report the treatment effects of a single area rather than the concomitant treatment of all upper facial indications. The purpose of this study was to evaluate the efficacy, safety, and subject satisfaction of ABO for the treatment of GL, LCL, and forehead lines (FLs).

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Methods

This article presents data from the first 6 months of a larger study (ID clinicaltrials.gov NCT02297516), which was an evaluator-blinded, within-group comparative, multicenter study of the efficacy, safety, and subject satisfaction of combined versus singletreatment. The larger study compared combined treatment with ABO, hyaluronic acid dermal fillers (Restylane and Emervel ranges, Galderma, Sweden), and Restylane skinboosters with ABO alone or fillers alone. The 6-month follow-up data presented herein are from the cohort that received ABO alone at baseline for the treatment of upper facial lines.

The study was conducted in accordance with the recommendations of the International Conference on Harmonization Good Clinical Practice Guideline and was consistent with the principles of the Declaration of Helsinki. Ethics committee approval was obtained. All subjects provided signed, informed consent.

Subjects aged 35 to 50 years with the intention to undergo facial aesthetic treatment of at least 2 upper facial indications, nasolabial folds and/or cheeks, and facial skin rejuvenation were eligible to participate in the study. Upper facial lines to be treated were graded as moderate or severe. Exclusion criteria comprised obvious facial sagging (major loss of facial fat/volume); signs or symptoms of eyelid ptosis or signs of compensatory frontalis muscle activity; heavily scarred or sun-damaged facial skin; treatment for rejuvenation within the previous 12 months (botulinum toxin, soft-tissue augmentation, hyaluronic acid–based or collagen-based treatments); procedures or treatments inducing an active dermal response within the previous 6 months (laser, intense pulsed light, chemical peeling, microdermabrasion, and retinoids); any aesthetic surgery of the face; and permanent implant or aesthetic facial treatment with non-HA or noncollagen products.

At baseline, subjects received a single treatment with ABO injection in at least 2 indications in the upper face. Injection sites followed ABO consensus recommendations.11 The recommended dose was 50 Speywood units (s.U.) in 5 injection points for GL; 60 s.U. (30 s.U. per side) in 3 injection points per side for LCL; and 20 to 60 s.U. in 4 to 6 injection points for FL. However, the total maximum dose should not exceed 125 s.U. An optional touch-up was allowed for 2 weeks after baseline. Follow-up visits were scheduled at 1, 3, and 6 months.

Wrinkle severity of GL, LCL, and FL was assessed by the investigator using 5-grade wrinkle severity scales.12 Responder rates were based on the percentage of subjects with at least 1-grade improvement on the individual scales. Global aesthetic improvement was assessed both by the subjects and the investigator. Subject and investigator satisfaction was evaluated by questionnaires. Subjects were questioned about their treatment expectations, appearance, satisfaction, skin quality, and psychosocial factors. The questions asked were related to the entire face and not specifically related to the treated area. Subjects were also asked to rate their satisfaction with the quality of their skin in relation to hydration, elasticity, softness, glow, freshness, structure, and firmness. The safety of the treatment was assessed by occurrence of adverse events (AEs).

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Results

Thirty-two subjects were enrolled in the ABO cohort, but 1 subject was withdrawn after receiving the baseline touch-up injection. Subject characteristics are shown in Table 1. At baseline, all subjects were treated with ABO in the GL and LCL, and 27 subjects were also injected in the FL. Fifteen subjects received touch-up injection after 2 weeks. The total mean dose injected per subject was 118.8 ± 13.0 s.U. A summary of the doses per area and number of injection points is shown in Table 2.

TABLE 1

TABLE 1

TABLE 2

TABLE 2

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Efficacy Evaluations

Wrinkle Severity at Maximum Contraction

Baseline wrinkle severity is shown in Table 3 and the proportion of responders at maximum contraction is presented in Figure 1. All subjects demonstrated a response to GL treatment with ABO at Month 1, defined as at least 1-grade improvement. At Month 3, 84% of the subjects were responders and 36% sustained a response until Month 6. A 2-grade improvement was recorded for 48% of subjects at Month 1, and 16% had a 3-grade improvement. Responders to LCL treatment were 94% of the subjects at Month 1, 71% at Month 3, and 23% continued to show a response at Month 6. In addition, 29% of subjects also demonstrated a 2-grade improvement at Month 1. For FL treatment with ABO, 93% of the subjects recorded a treatment response at Month 1, 70% at Month 3, and 22% maintained this response at Month 6. A 2-grade improvement was observed in 63% of subjects at Month 1, and 7% showed a 3-grade improvement. A Wilcoxon signed rank test of wrinkle severity scores for ABO treatment versus baseline showed significant p-values (p ≤ .05) for all timepoints except for LCL and FL at Month 6. Clinical aesthetic results describing the appearance of upper facial lines are shown in Figure 2.

TABLE 3

TABLE 3

Figure 1

Figure 1

Figure 2

Figure 2

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Wrinkle Severity at Rest

Figure 3 shows the proportion of responders receiving ABO for each upper facial indication at rest. For GL, 61% of subjects were graded as responders at Month 1, presenting at least 1-grade improvement. At Month 3, 55% of the subjects demonstrated a treatment response and 39% continued to show a response at Month 6. A 2-grade improvement was recorded for 10% of subjects at Month 1. In total, 68% of subjects responded to LCL treatment with ABO at Month 1, 36% at Month 3, and 23% at Month 6. Moreover, 7% of subjects had a 2-grade improvement at Month 1. Forehead line treatment with ABO resulted in 96% of the subjects recording a response at Month 1, 85% at Month 3, and 59% continued to show a response at Month 6. A 2-grade improvement was achieved in 41% of subjects at Month 1, and 4% had a 3-grade improvement. Clinical aesthetic results in the appearance of FHL at rest are seen in Figure 4. A Wilcoxon signed rank test of wrinkle severity scores for ABO treatment versus baseline showed significant p-values (p ≤ .001) for all timepoints except for LCL at Month 6.

Figure 3

Figure 3

Figure 4

Figure 4

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Global Aesthetic Improvement

The percentage of subjects showing improvement across the study period according to both subject and investigator assessments is shown in Figure 5. All subjects improved at Month 1 according to both investigator and subject assessments.

Figure 5

Figure 5

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Subject Satisfaction

When asked at baseline, “What effects are you seeking from the treatment,” the most common response was “wanting to improve overall facial appearance” (88%), followed by “preventing signs of ageing” (81%) and “feeling better about myself” (56%). Before treatment, 31% of the subjects reported being “very satisfied” or “somewhat satisfied” with the appearance of their face. After treatment, 87% stated they were “very satisfied” or “somewhat satisfied” at Month 1, 77% at Month 3, and 55% at Month 6. Five subjects (16%) stated they were very dissatisfied with the appearance of the face at baseline; none of the subjects reported “very dissatisfied” at any of the follow-up visits.

At 1, 3, and 6 months after treatment, 61, 55, and 39% of subjects, respectively, reported that they felt “much better” or “very much better” about themselves. In total, 81% of subjects confirmed they were “very satisfied” or “somewhat satisfied” with the treatment after 6 months (Figure 6). Investigators reported that they were “somewhat satisfied” or “very satisfied” with the overall facial aesthetic outcome for 84% of subjects at Month 1.

Figure 6

Figure 6

After ABO treatment of GL, LCL, and FL, more than 70% of subjects felt “very satisfied” or “somewhat satisfied” with their level of skin hydration, elasticity, softness, glow, freshness, structure, and firmness, 6 to 7 months after treatment.

Subjects were asked a series of questions related to how they felt about themselves at baseline and throughout the study. After treatment, the results were generally positive at every timepoint, and even 6 months afterward, around half of the subjects reported that they “agreed” or “strongly agreed” that the treatment improved their attractiveness (52%), facial symmetry/balance (48%), and self-esteem (52%). Subjects also confirmed that the treatment made them feel better about themselves (55%); that they had improved life satisfaction and contentment (48%); that the treatment made them look and feel more successful (32%); that they looked younger than their age (29%); and that they looked the way they felt (52%). One month after the treatment, 100% of subjects said they would recommend the treatment to a friend and would have the treatment again.

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Safety

There were no serious AEs reported throughout the study. In total, 19 nonserious AEs were reported in 16 subjects; 8 treatment-related (7 subjects) and 11 non–treatment-related (11 subjects). All the treatment-related AEs were mild or moderate (Table 4) and completely resolved in 6 months with the exception of a mild eyelid edema in one subject (3%). Headache was the most common treatment-related AE (3 events in 3 subjects [9%]). Other treatment-related AEs were 1 case of eyelid sensory disorder (3%), 1 case of injection-site bruising (3%), and injection-site edema (2 events in 1 subject [3%]). No cases of brow ptosis were recorded.

TABLE 4

TABLE 4

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Discussion

The results of this clinical study indicate that ABO alone effectively treated upper facial lines, with a good safety profile and high patient satisfaction. High efficacy was obtained, as 100% of the patients had at least 1-grade improvement in dynamic wrinkles from baseline in GL, and more than 92% for LCL and FL. Effects in dynamic wrinkles lasted for 3 months after treatment in 70% to 84% of the patients, and in 22% to 36% of the patients for 6 months after treatment. There was a marked improvement in wrinkle severity at rest, particularly concerning FL, with 96% of subjects experiencing at least 1-grade improvement 1 month after treatment.

These results showed that the average dose (29 s.U.) used in FL treatment (recommended by the consensus12) was suitable for the treatment of hyperkinetic lines and FL at rest. AbobotulinumtoxinA treatment was generally well-tolerated and associated with high patient satisfaction. The use of botulinum toxins for aesthetic improvement of horizontal FLs requires careful consideration concerning the positioning and shape of the eyebrows and the tension of the frontalis muscle, as treatment may be associated with brow ptosis.13 Of note, mild eyelid edema and eyelid sensory disorder were self-reported but not noticed by the investigator.

By reducing muscle movement, improvement can be seen not only in dynamic wrinkles but also in the static ones. In this study, improvements were observed in some static wrinkles and were more evident in patients presenting with mild static wrinkles. The reduction of static lines with maintenance of some muscle activity, as observed in this study, was a desired and expected result. It avoids a frozen look and improves facial aesthetics, as subjects change the way they use their facial muscles, not only the treated ones.

Concomitant treatment of different ABO indications is commonly used in clinical practice with good results. Some publications have addressed the safety and efficacy of concomitant treatment as well as patient satisfaction and quality of life.4–6,9,10,14 Hexsel and colleagues9 assessed the treatment of the upper, middle, and lower third of the face concomitantly. Significant improvement was observed for GL, LCL, and FL 4 months after treatment and for more than 6 months for GL.

Although methodological differences make it impossible to directly compare our outcomes with those of similar studies examining concomitant administration of other botulinum toxins,3,6 our results provide further evidence concerning the benefits of ABO in achieving at least 1-grade reductions in upper facial line severity and significant improvements in global aesthetic appearance over a 6-month period.

Subject satisfaction is highly important in aesthetic treatment of the upper face, as it impacts a person's perception of their appearance, their quality of life, and self-confidence.15 Satisfaction with a procedure influences a person's decision to continue with a treatment or recommend it to others.11 It has also been suggested that treating multiple upper facial areas, rather than the glabellar area only, leads to greater improvements in self-perception scores and a higher number of subjects perceiving themselves as looking younger than their actual age.15 Treatment of multiple facial areas has been reported to result in improved subject satisfaction and quality of life.14

In this study, we observed an improvement in how the subjects felt about themselves with 87, 77, and 55% of subjects reporting satisfaction with the appearance of their face at 1, 3, and 6 months, respectively. These results are higher than those previously reported by de Boulle and colleagues.16 Furthermore, 81% of subjects confirmed that they were satisfied with the treatment after 6 months. Global aesthetic improvement results were also in line with subject satisfaction. There was a high degree of subject satisfaction with skin quality, reflected in subject satisfaction questionnaires.

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Conclusion

AbobotulinumtoxinA is an effective and well-tolerated intervention for the concomitant treatment of the studied upper facial indications. Glabellar lines, lateral canthal lines, and forehead lines improved both at maximum frown and at rest. High global aesthetic improvement and subject satisfaction were maintained over 6 months.

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References

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