In aesthetic medicine, patient satisfaction is a strong motivating factor for patient retention1 and benefits of treatments go well beyond aesthetic improvements.2 To provide harmonious results, a full-facial approach should be adopted, taking the 3-dimensional aspects of aging into account.3 Botulinum toxin type A (BoNT-A) and soft-tissue hyaluronic acid (HA) fillers can be used in combination for injection at multiple tissue levels and in different facial areas to correct static wrinkles, volume loss, and structural failure.3–53–53–5
BoNT-A (Speywood Unit; s.U) (Abobotulinum toxin A) (Azzalure; Ipsen Pharma, Boulogne-Billancourt, France) is an efficacious and safe option for the treatment of facial wrinkles indicated for moderate to severe glabellar lines.6–116–116–116–116–116–11
In addition, a range of nonanimal stabilized HA dermal fillers Restylane (RES) have been developed and studied for facial soft-tissue augmentation.12–1512–1512–1512–15
Although full-facial treatments are currently adopted in real practice, they have been investigated only in a few studies. There is still a lack of information on combination treatments with BoNT-A and fillers, and how the results of full-facial treatments are appreciated by the patients.16,1716,17 This study evaluated the subject satisfaction, efficacy, and safety of BoNT-A (s.U) and the RES filler range in combination for full-facial aesthetic rejuvenation.
Methods and Subjects
This was a 6-month multicenter, open-label clinical study performed in 6 clinical centers in France, Spain, and the United Kingdom. The study included male and female subjects, aged 18 to 64 years, seeking treatment for correction of dynamic wrinkles on the upper third of the face, and correction of facial volume loss in the mid and lower face. Subjects who had previously undergone a surgical facelift or had permanent dermal fillers in the face were excluded from the study. Subjects with previous, nonpermanent soft-tissue augmentation or BoNT-A treatment could be included following a washout period of at least 6 months. The study was approved by the local Ethics Committee and Health Authorities and was conducted according to Good Clinical Practice and the ethical guidelines of the Declaration of Helsinki. All subjects gave their informed written consent before participation.
At baseline, investigators administered BoNT-A (s.U) as follows: for glabellar lines, 5 injection points with 10 s.U/point; for the horizontal forehead lines, 4 to 6 injections with 5 to 10 s.U/point; for lateral canthal lines, 3 injections per side with 10 s.U/point. The HA gel filler range (Restylane range; Q-Med AB, Uppsala, Sweden) comprised Restylane Lidocaine (HA-R), Restylane Perlane Lidocaine (HA-P), Restylane Sub-Q Lidocaine (HA-Q), Restylane Lip Volume (HA-LV) and Restylane Lip Refresh (HA-LR). The area to be treated was chosen by the investigator based on the protocol and subject expectations. Touch-up injection(s) could be performed 3 weeks after the first injections.
Study Evaluation and Clinical Outcomes
Subjects completed a satisfaction questionnaire 3 weeks and 6 months after the last injection, as well as the World Health Organization-Five Well-Being Index (WHO-5) (1998 version) and the Heatherton & Polivy State Self-Esteem Scale (HPSS)18 questionnaires at each evaluation time.
Clinical evaluations were performed at baseline (before first injection), 3 weeks, 4 months, and 6 months post-injection. Global aesthetic improvement from baseline was rated by the investigator and by the subjects at each postbaseline study visit using the Global Aesthetic Improvement Scale (GAIS), a 5-point scale from −1 (worse) to 3 (very much improved).19 Lateral canthal lines and glabellar lines were scored at rest and at maximum contraction by the investigators at each evaluation time using a 4-point severity scale from 0 (none) to 3 (severe).20,2120,21 Forehead wrinkle severity was scored on a 4-point scale from 0 (none) to 3 (severe).22 Nasolabial folds, marionette lines, and upper lines were scored using the Lemperle Rating Scale, a 5-point scale from 0 (no wrinkles) to 5 (very deep wrinkle, redundant fold).23 Lip enhancement was assessed based on the Lip Fullness Grading Scale, a 5-point scale from 0 (very thin lip) to 4 (full lip).24 The tear trough depth was scored on a 5-point scale from 0 (0 mm) to 4 (4 mm).25 For cheeks, cheekbones, chin and jawlines, the investigator aesthetic improvement from baseline was rated using a 5-point GAIS scale. In addition, the lifting effect was assessed by the investigator compared with baseline photographs, using a 5-point scale from 0 (worsening) to 4 (extremely effective). Adverse events (AEs) reported by the subject or observed by the investigator were recorded at each study visit.
Data Handling and Statistical Methods
Statistical analyses were carried out on the intent-to-treat population, including all enrolled subjects. All variables and/or changes from baseline (before first injection) were described using usual statistics for quantitative or qualitative data accordingly. When the right/left areas were injected and evaluated, the worst scores across both sides were used for qualitative variables and the mean between sides for continuous variables. No inferential analysis was performed except for the quality-of-life (QoL) questionnaires, where the differences from baseline were tested using the Wilcoxon signed-rank test.
Participants and Injection Information
Sixty subjects were enrolled with a mean age of 47.6 years. Of those, 57 subjects completed the 6-month follow-up, whereas 3 subjects (5%) discontinued (1 due to unrelated serious AE, and 2 lost to follow-up). Most of them had moderate to severe wrinkles or folds in the upper, mid, and lower face (Table 1).
The 3 upper face indications were the most frequently treated sites: lateral canthal lines in 96.7% of subjects, glabellar lines in 95.0%, and forehead wrinkles in 73.3%. Nasolabial folds and marionette lines were the most frequently treated sites in the mid and lower face (73.3% and 68.3% of subjects, respectively), followed by cheekbone (63.3%) and cheek (56.7%) augmentation (Figure 1). Overall, most subjects (63.3%) were treated for 6 to 9 indications with a median of 8.
The HA products used for each zone are summarized in Figure 2. HA-P was the most frequently used filler followed by HA-R. When treated, nasolabial folds, marionette lines, jawline, tear trough, the chin and temples were most frequently treated with HA-P. The 2 volumizing indications (cheekbones and cheeks) were mostly treated with HA-Q, and upper lip lines were exclusively treated with HA-R. HA-LV and HA-LR were used in 25.0% and 30.0% of subjects, respectively.
Three weeks after the last injection, 96.5% of subjects were satisfied/very satisfied with the overall full-facial aesthetic outcome, and the treatment met/surpassed the expectations of 96.5% of subjects (Figure 3A,B); 80.7% had received positive/very positive feedback about their looks. In addition, 96.5% agreed/strongly agreed that the overall treatment result looked natural, 91.4% that they looked more the way they felt, and 86.0% that they felt more attractive.
Six months after the last injection, subjects were still satisfied/very satisfied (92.9%) with the overall full-facial aesthetic outcome and the treatment expectation was met/surpassed (91.2%) (Figure 3A,B). Overall, 92.8% of subjects were satisfied/very satisfied regarding the durability of the results (Figure 3C), and 91.2% of subjects felt better since the injections were performed (Figure 3D). Regarding future treatment, 94.5% of subjects would recommend such treatment, and 96.4% would like to receive the same treatment again.
Three weeks after the last injection, a global aesthetic improvement was obtained in 100% of subjects according to investigators and subjects (Figure 4). The improvement was sustained up to 6 months for 96.6% and 94.8% according to investigators and subjects, respectively (Figures 5–7Figures 5–7Figures 5–7).
A decrease in mean severity scores and an increase in Lip Fullness Grading Scale scores showed improvement of all treatment areas at 3 weeks after the last injection and this improvement was in the mid and lower face (Table 2). In addition, the investigator rated the lifting effect as at least effective in 96.7% and 79.0% of subjects 3 weeks and 6 months after last injection, respectively.
Quality of Life
According to the WHO-5 QoL questionnaire total score, there was a statistically significant increase at 3 weeks (p = .008) and 4 months (p = .037) compared with baseline, indicating an improvement in QoL. At 6 months, a trend of improvement was still observed (not statistically significant) (data not shown). The self-esteem questionnaire, indicated a higher self-esteem with a statistically significant increase from baseline in HPSS total score at 3 weeks (p < .001), 4 months (p = .002), and 6 months (p = .006).
The total mean injected dose per subject for BoNT-A (s.U) was 136 ± 48.0 s.U (range, 40–292 s.U), whereas for RES products it was 7.9 ± 5.0 mL (range, 2.3–19.4 mL).
Overall, 14 subjects (23%) reported a total of 29 treatment-related AEs. These AEs were mild in intensity (except 1 moderate bruising and 1 moderate skin swelling), and resolved spontaneously. One AE (eyelid ptosis) was related to BoNT-A (s.U) and 28 AEs were related to RES fillers (skin swelling in 9 subjects, and bruising in 4 subjects). Two subjects experienced serious AEs (1 cerebral infarction and 1 colon cancer) not related to treatment.
This study assessed the satisfaction of subjects treated with BoNT-A (s.U) and HA fillers for full-facial rejuvenation. Most previous clinical studies in facial treatment generally showed a high subject satisfaction.2,26–282,26–282,26–282,26–28 However, these studies are restricted to a limited number of treatment areas using one or a few HA fillers. In the present study, a complete facial treatment (up to 13 treatment areas) combining BoNT-A (s.U) and HA fillers produced an overall aesthetic improvement, with high subject satisfaction sustained up to 6 months after the last injection. Moreover, there is a lack of data that assess parameters including youthful appearance, natural look, harmony, or psychosocial parameters. In this study, most subjects reported that the combined full-facial treatment produced a natural look at 3 weeks and that the durability of results up to 6 months was satisfactory/very satisfactory. Consequently, approximately 95% of subjects reported that they would recommend injections to family or friends and that they would like to receive the same treatment again. These results are consistent with the idea that the primary expectation in patients seeking minimally invasive facial procedures is to look as natural as possible to reflect the personality and expression, and to protect inner contentment or self-esteem.29
The current literature suggests that a number of psychosocial domains may be improved following facial cosmetic procedures30 and a high satisfaction probably mediates more well-being and self-esteem. Full-facial treatment may reduce negative mood and affect QoL.31 Dayan and colleagues32 reported that treatment of facial wrinkles with BoNT-A significantly improved QoL parameters related to enjoyment, satisfaction with life, and self-esteem 2 weeks and 3 months after treatment. In our study using 2 validated QoL questionnaires (WHO-5 and HPSS), the subjects' well-being and self-esteem were still significantly improved up to 4 and 6 months, respectively, after full-facial treatment.
More than 96% of subjects were satisfied with the full-facial aesthetic outcome at 3 weeks and approximately 93% at 6 months. This high level of satisfaction was consistent with the GAIS assessed by the investigators or subjects. Injections at individual zones were effective and efficacy/durability results were consistent with previous reports on glabellar lines, crow's feet, nasolabial folds, and other periorbital zones.8,128,12 The lifting effect remained enhanced in 79.0% of subjects 6 months after the injection.
This study provides information on the sites of injection and doses of BoNT-A (s.U) and RES filler range, which could be used in combination in different zones for full-facial rejuvenation. The high volume of HA used is consistent with that of similar studies of HA fillers.27,2827,28 Combination of HA fillers in the full face with BoNT-A (s.U) in the upper face was well tolerated with no particular safety concern.
In this study, large quantities of products were used, which would be associated with a high cost for this treatment. Therefore, the high patient satisfaction observed might not simulate precisely patient expectations in a clinical setting. Although this study is limited by the noncomparative, open-label design, it included a relatively high number of subjects compared with similar studies of facial rejuvenation. The high level of safety and efficacy obtained for full-facial rejuvenation using a combination of treatments is consistent with a previous study,33,3433,34 suggesting that full-facial treatment with various products leads to a better outcome or longer duration than treatment with each product alone.
In conclusion, full-facial treatment combining BoNT-A (s.U) and RES fillers led to a holistic improvement of global aesthetic outcomes and a sustained effect observed up to 6 months after injection. Treatment of a single facial area may often be suboptimal and therefore, the face should be evaluated and treated as a whole. In combination treatment, muscle inactivation by BoNT-A (s.U) may ultimately improve durability of HA fillers, thus prolonging aesthetic improvement and subject satisfaction. The treatment fulfilled subject expectations, particularly in terms of natural look, durability of treatment, inner contentment, self-esteem, QoL and was safe and well tolerated.
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© 2015 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.
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