Abstract
Background
Panfacial treatment has the potential to positively impact psychosocial and emotional well-being.
Objectives
The Canada HARMONY study evaluated the satisfaction and psychosocial impact of comprehensive, multimodal aesthetic treatment of the face and submental area from the patient perspective.
Methods
Over 12 months, all patients (N = 58) sequentially received treatment with hyaluronic acid (HA) fillers, onabotulinumtoxinA, and medical-grade skincare products, and eligible patients (n = 13) also received ATX-101. The primary endpoint was the change from baseline on the FACE-Q Satisfaction with Facial Appearance Scale. Secondary endpoints included the following assessments: FACE-Q Expectations of Life Change, Psychological Function, Social Function, Satisfaction with Skin, and Aging Appraisal Scales; Global Aesthetic Improvement Scale (GAIS); and the Periorbital Aesthetic Appearance Questionnaire (PAAQ). Safety was monitored throughout the study.
Results
Baseline FACE-Q Expectations of Life Change scores indicated realistic treatment expectations. Significant improvements from baseline were observed on the FACE-Q Satisfaction with Facial Appearance, Psychological Function, Social Function, Satisfaction with Skin, and Aging Appraisal Scales (P < .0001 for all endpoints). Most patients rated “much improved” on the GAIS. The mean PAAQ total score significantly improved from baseline by 32.6 (P < .0001). Most patients reported mild-to-moderate injection-site responses, which had a mean time to resolution of <14 days.
Conclusions
Panfacial aesthetic treatment consisting of HA fillers, onabotulinumtoxinA, and ATX-101 improved patient-reported satisfaction, psychological function, social function, and aging appraisal across validated measures.
Level of Evidence: 5 (Therapeutic)
Patient satisfaction is the cornerstone of aesthetic treatment goals. The expanding range of minimally invasive treatment options, including soft-tissue fillers, botulinum toxin type A, and skincare products, has enabled clinicians to better meet the needs of patients.1,2 Furthermore, the increased availability of these treatments to address different facial needs, including facial aging and the enhancement of beauty or wellness, allows for a comprehensive panfacial approach to aesthetic treatment.3-8 A panfacial approach extends beyond treatment of lines and folds to consider facial harmony and balance by addressing multiple areas concurrently rather than treating individual areas of the face.9,10
Several studies support the potential benefits of panfacial aesthetic treatment by providing outcomes superior to treatment of individual problem areas in the domains of improved patient satisfaction, psychological function, and improved onlooker perceptions.1,9,11-13 The US HARMONY study provided the first comprehensive assessment of multimodal, minimally invasive facial aesthetic treatment outcomes.9 Patients received hyaluronic acid (HA) fillers (HYC-24L, Juvéderm Ultra XC with Lidocaine; HYC-24L+, Juvéderm Ultra Plus XC with Lidocaine; VYC-20L, Juvéderm Voluma with Lidocaine) for treatment of facial lines and folds and volume restoration, onabotulinumtoxinA for facial rhytids (glabellar lines [GLs] and crow's feet lines [CFLs]), and bimatoprost 0.03% ophthalmic solution for eyelash hypotrichosis (all products, Allergan Aesthetics, an AbbVie Company, Irvine, CA).9 At 4 months posttreatment, there was a statistically significant improvement from baseline on the FACE-Q Satisfaction with Facial Appearance Scale (P < .0001), which included items relating to satisfaction/dissatisfaction with the symmetry, balance, proportion, and freshness of one's appearance.9 Significant psychological benefits of multimodal treatment from the same study have also been reported.13
The US HARMONY study demonstrated the benefits of multimodal aesthetic treatment to improve facial appearance9,13; however, onabotulinumtoxinA was limited for treatment of GLs and CFLs and VYC-20L for midface volume loss. Furthermore, the study did not include treatment of the submental area using deoxycholic acid injections (ATX-101, Kybella/Belkyra; Allergan Aesthetics, an AbbVie Company, Irvine, CA) or use of skincare products. The objective of the Canada HARMONY study was to evaluate satisfaction and psychosocial impact from the patient perspective of comprehensive, multimodal aesthetic treatment of the face and submental area. Therefore, the current study included onabotulinumtoxinA for treatment of GLs, CFLs, and forehead lines (FHLs); a variety of Juvéderm fillers for treatment of facial skin quality, lines, folds, and volume loss; ATX-101 for treatment of submental fat (SMF); and medical-grade skincare products.
METHODS
Study Design
Canada HARMONY was a prospective, single-arm, open-label, postmarketing study (NCT03712449) conducted at 7 sites in Canada from January 22, 2019 to July 29, 2020. Patients received combined treatments (all products, Allergan Aesthetics, an AbbVie Company), including HA fillers VYC-12L (Juvéderm Volite with Lidocaine), VYC-15L (Juvéderm Volbella with Lidocaine), and VYC-17.5L (Juvéderm Volift with Lidocaine) for treatment of facial skin quality, lines, and folds; VYC-15L (Juvéderm Volbella with Lidocaine) for volume restoration in the lips and for treatment of perioral lines, oral commissures, and the infraorbital area; and VYC-20L (Juvéderm Voluma with Lidocaine) for volume restoration in the chin, cheek, and malar area. Patients also received onabotulinumtoxinA for treatment of upper facial rhytids (GLs, CFLs, and FHLs), as well as medical-grade, topical nonprescription skincare products (SkinMedica facial cleanser [Facial Cleanser], serum [TNS Essential Serum], moisturizer [Rejuvenative Moisturizer], and optional sunscreen [Total Defense + Repair Broad Spectrum Sunscreen SPF34]), which may be used at the patient's discretion. A subset of patients with moderate-to-severe submental fullness received between 1 and 6 ATX-101 treatments before receiving all other treatments. Treatments were administered over 12 months, and outcomes were compared with baseline before treatment (Figure 1).
Figure 1.
Study design. For patients who received ATX-101 treatment, V1 was the first treatment day, and V2 to V7 occurred at least 30 days (1 month) after the previous visit (ATX-101 treatment). V7 was the first treatment day for HA fillers and skincare products, and V10 was the first treatment day for onabotA. V8 to V11 occurred at least 1 month after the previous visit/treatment. V12, which is 1 month after the previous visit/treatment, is the final study visit when all primary and secondary endpoints were collected. HA, hyaluronic acid; onabotA, onabotulinumtoxinA; V, visit.
The study protocol, informed consent form, and treating investigators were approved by a research ethics board (ADVARRA, Aurora, ON, Canada). The study was conducted in accordance with standard operating procedures that met the International Council for Harmonisation E6 Good Clinical Practice guidelines and the most recent revision of the Declaration of Helsinki. Each patient provided written informed consent before enrollment.
Patients
Eligible patients were aged 30 to 65 years and had moderate-to-severe facial volume loss qualifying for facial filler treatments as assessed by the treating physician, mild-to-moderate facial photodamage (based on a score of 1-9 on the SkinMedica Overall Photodamage Scale), and moderate-to-severe facial rhytids (GLs, CFLs, or FHLs) as measured on the Facial Wrinkle Scale. All patients agreed not to receive any other facial procedures or treatments at any time during the study that were not related to the study. Patients receiving ATX-101 had moderate-to-severe submental fullness (Grade 2 or 3 on the clinician-reported Submental Fat Rating Scale; CR-SMFRS) and patient-reported dissatisfaction with the submental area (rating of 0, 1, or 2 on the Subject Self-Rating Scale).
Patients were excluded if they had a grade of 4 on the CR-SMFRS; BMI > 30 kg/m2; received onabotulinumtoxinA or treatment with any other botulinum toxin product within 6 months before enrollment; undergone temporary or semi-permanent facial or neck dermal filler treatment within 12 months before enrollment; received mesotherapy or skin resurfacing in the face or neck within 6 months before enrollment; or prior or planned plastic surgery of the face and/or neck, tissue grafting, or tissue augmentation. Patients receiving ATX-101 were excluded if they had a history of any intervention to treat SMF (eg, liposuction, surgery, and lipolytic agents); history of trauma in the chin or neck area; submental area enlargement other than SMF; an anatomical feature for which SMF reduction may result in an aesthetically unacceptable outcome; or any medical condition that could interfere with the safety, efficacy, or administration of ATX-101.
Treatments
All patients received treatment with 1 or more HA fillers, with 2 optional touch-ups spaced 1 month apart and beginning 1 month after initial treatment. The appropriate volume injected was determined by the investigator. Maximum volumes for VYC-12L, VYC-15L, and VYC-17.5L include the initial and touch-up treatments combined. VYC-12L was injected to a maximum of 4 mL in fine facial lines. VYC-15L was injected to a maximum of 2 mL for lips, 1.5 mL for oral commissures, 1.2 mL for perioral lines, and 1.5 mL for the infraorbital area. VYC-17.5L was injected to a maximum of 4 mL in the nasolabial folds. VYC-20L was limited to a maximum of 6 mL (2 mL each for the cheek, chin, and malar area) during each session. Medical-grade skincare products were applied daily for ∼4 months after the first HA filler treatment until study completion.
After receiving filler treatment, all patients received at least 1 of the following treatment regimens with onabotulinumtoxinA per the approved indication, with 1 optional touch-up. For GLs, injections were a single 0.1-mL injection in the procerus muscle and 2 0.1-mL injections bilaterally in each corrugator muscle (20 U total; 5 injection sites). For CFL, each injection was 0.1 mL (36 U total; 2-6 U injected bilaterally in 1-3 sites per side). For FHLs, each injection was 0.1 mL (24 U total; 2-6 U injected at 4 sites into the frontalis muscle).
The subset of patients treated with ATX-101 received a maximum of 10 mL per session (0.2 mL into the subcutaneous fat at each site). The number of sessions needed to achieve a satisfactory response varied among patients. Up to 6 treatments at intervals of no <1 month apart were allowed. The final ATX-101 treatment was completed at least 1 month before the initial HA filler treatment.
Assessments
Details of the endpoints assessed in this study and scale descriptions are shown in Table 1. The primary endpoint was change from baseline to final study visit on the validated FACE-Q Satisfaction with Facial Appearance Scale.14 Raw scale summed scores ranging from 10 to 40 were converted to a Rasch-transformed score ranging from 0 to 100, with higher scores reflecting a better outcome.
Table 1.
Primary and Secondary Endpoints
| Assessment | Endpoint | Description | Scoring |
|---|---|---|---|
| Primary endpoint | |||
| FACE-Q Satisfaction with Facial Appearance Scale | Change from baseline to final study visit | 10 items evaluating one's appearance using concepts, such as facial symmetry, balance, proportion, and freshness, as well as under different conditions (feeling rested, profile view, in photographs, when waking up, at the end of the day, and under bright lights) | 4-point scale: 1 = very dissatisfied 2 = somewhat dissatisfied 3 = somewhat satisfied 4 = very satisfied |
| Secondary endpoints | |||
| FACE-Q Expectations of Life Change Scale | Baseline score | 8 items assessing how a patient expects their appearance and life to change after a body or facial aesthetics procedure | 4-point scale: 1 = definitely disagree 2 = somewhat disagree 3 = somewhat agree 4 = definitely agree |
| FACE-Q Psychological Function Scale | Change from baseline to final study visit | 10 items assessing how patients feel about themselves when considering their facial appearance | 4-point scale: 1 = definitely disagree 2 = somewhat disagree 3 = somewhat agree 4 = definitely agree |
| FACE-Q Social Function Scale | Change from baseline to final study visit | 8 items assessing how a patient's facial appearance affects their confidence in social situations | 4-point scale: 1 = definitely disagree 2 = somewhat disagree 3 = somewhat agree 4 = definitely agree |
| FACE-Q Satisfaction with Skin Scale | Change from baseline to final study visit | 12 items assessing the patient's satisfaction with the appearance and complexion of their facial skin | 4-point scale: 1 = very dissatisfied 2 = somewhat dissatisfied 3 = somewhat satisfied 4 = very satisfied |
| FACE-Q Aging Appraisal Scale | Change from baseline to final study visit | 7 items assessing patient feelings about how old their face looks in photographs or in a mirror | 4-point scale: 1 = definitely disagree 2 = somewhat disagree 3 = somewhat agree 4 = definitely agree |
| Global Aesthetic Improvement Scale (GAIS) | Investigator's and patient's assessment at final study visit | Investigator assessment: the level of improvement to the patient's facial lines in person at the final study visit compared with the patient's photographic image obtained at baseline Patient assessment: the level of improvement to their own appearance in a mirror at the final study visit compared with their image obtained at baseline |
5-point scale: 2 = Much improved 1 = Improved 0 = No change 1 = Worse 2 = Much worse |
| Periorbital Aesthetic Appearance Questionnaire (PAAQ) | Patient's assessment at final study visit | 9 questions assessing the patient's periorbital area over the past 7 days, categorized according to psychological, appearance, and coping domains Psychological domain: 5 items evaluating how the overall eye appearance makes the patient feel older, less attractive, self-conscious, and sad, and the need to wear makeup Appearance domain: 3 items evaluating how the overall eye appearance makes the patient look older, less attractive, and tired Coping domain: 1 item evaluating how often the patient takes attention away from the overall eye area other than by wearing makeup (eg, wearing sunglasses, and styling hair) |
5-point scale (calculated for each domain): 0 = never 1 = rarely 2 = some of the time 3 = most of the time 4 = all of the time Patient responses to items in all 3 domains are transformed to a scale of 0 to 100 to produce a total score |
Key secondary endpoints included the baseline score for the validated15 FACE-Q Expectations of Life Change Scale, and the change from baseline to final study visit in the following validated15 FACE-Q Scales: Psychological Function, Social Function, Satisfaction with Skin, and Aging Appraisal. Raw scale summed scores were converted to Rasch-transformed scores, ranging from 0 to 100. Improvements in the FACE-Q Satisfaction with Facial Appearance, Psychological Function, Social Function, and Satisfaction with Skin Scales are associated with positive responses (satisfaction/agreement), whereas improvements in the FACE-Q Aging Appraisal Scale are associated with negative responses (disagreement).
Additional secondary measures utilized the investigator- and patient-assessed Global Aesthetic Improvement Scale (GAIS) and the validated Periorbital Aesthetic Appearance Questionnaire (PAAQ).
Safety
All adverse events (AEs), including serious AEs, and injection-site responses (ISRs) were collected from the time of consent to the final study visit.
Statistical Analysis
Data were summarized with descriptive statistics. Hypothesis testing was 2-sided, performed at a 0.05 significance level.
The full analysis population, defined as all patients who met eligibility criteria and received any treatment during the study, was used to analyze disposition, demographics, baseline characteristics, and safety. The evaluable population, defined as all patients in the full analysis population with ≥1 posttreatment efficacy assessment at the final visit, was used for efficacy assessments. A sample size of 48 patients provided at least 90% power to determine whether the change from baseline to final study visit in the FACE-Q Satisfaction with Facial Appearance Scale Rasch-transformed score was different from 0, assuming a mean change (standard deviation [SD]) of 12.0 (20.0), based on a 1-sample, 2-sided t-test at a 5% significance level. The same analysis procedures and methods used for the primary efficacy endpoint were applied for the FACE-Q secondary efficacy endpoints, Psychological Function, Social Function, Satisfaction with Skin, and Aging Appraisal. For both the primary and secondary FACE-Q endpoints, FACE-Q interpretation tables were used to determine the average response.
RESULTS
Patients
Of the 59 patients enrolled, 58 received treatment and 1 patient withdrew consent before treatment initiation and was discontinued from the study. Of the 58 patients, 13 (22.4%) received ATX-101 treatment. The majority of patients were female (female, 51/58 [88%]; male, 7/58 [12%]) with Fitzpatrick skin phototype II or III and a mean (range) age of 52 (31-65) years (Table 2).
Table 2.
Patient Demographics
| Characteristics | Patients (N = 58) |
|---|---|
| Age, years | |
| Mean (SD) | 51.8 (7.3) |
| Min, max | 31, 65 |
| Female, n (%) | 51 (87.9) |
| BMI, kg/m2 | |
| Mean (SD) | 23.9 (3.2) |
| Min, max | 18.4, 29.9 |
| Fitzpatrick skin phototype, n (%) | |
| I | 0 |
| II | 29 (50.0) |
| III | 26 (44.8) |
| IV | 3 (5.2) |
| V | 0 |
| VI | 0 |
SD, standard deviation.
Study Treatments
For patients receiving ATX-101 treatment, the mean (SD) injection volumes per treatment session were the following: Visit 1, 7.4 (9.9) mL; Visit 2, 4.6 (1.2) mL; Visit 3, 4.4 (1.3) mL; Visit 4, 3.4 (0.9) mL; Visit 5, 3.4 (0.9) mL; and Visit 6, 2.0 (0.0) mL. Over the course of the study, the mean volumes administered for each filler (initial and touch-up treatments) were the following: VYC-12L, 2.8 mL, VYC-15L, 2.2 mL, VYC-17.5L, 3.0 mL, and VYC-20L, 6.6 mL.
Primary Endpoint Assessment
Patients showed significant (P < .0001) improvement from baseline to the final study visit on the FACE-Q Satisfaction with Facial Appearance Scale score, with a mean increase of 30.3 points (Figure 2). On average, baseline scores were associated with “somewhat dissatisfied” responses, and scores at the end of the study were associated with “somewhat satisfied” or “very satisfied” responses (Figure 3), indicating improvement in patients’ overall facial appearance. For example, 2 items that assessed how symmetric and balanced the patient's face looked were associated with a “somewhat dissatisfied” response at baseline and “very satisfied” response at the end of the study (Figure 3). For all items on the scale, 8.6% to 56.9% of the patients were “somewhat satisfied” or “very satisfied” at baseline compared with 79.3% to 98.3% at the end of the study.
Figure 2.
Mean (standard error) FACE-Q Satisfaction with Facial Appearance Scale total score at baseline and final visit.
Figure 3.
FACE-Q Satisfaction with Facial Appearance Scale responses, by item and response category. Blue circles and green squares indicate the average response at baseline and at the final visit, respectively.
Secondary Endpoint Assessments
FACE-Q Scale Scores
On average, most of the baseline scores on the Expectations of Life Change Scale were associated with “somewhat disagree” responses on items pertaining to fitting in and improving/forming new relationships, and “somewhat agree” responses on items pertaining to improving appearance and being transformed (data not shown). These responses indicate that baseline expectations were realistic.
Change from baseline to the final study visit indicated significant improvement on Psychological Function (P < .0001), Social Function (P < .0001), Satisfaction with Skin (P < .0001), and Aging Appraisal (P < .0001) Scales (Figure 4).
Figure 4.
Mean (standard error) change from baseline in FACE-Q Aging Appraisal, Psychological Function, Social Function, and Satisfaction with Skin Scales.
On average, most of the baseline scores on the Psychological Function Scale were associated with “somewhat agree” responses, whereas most mean scores at the end of the study were associated with “definitely agree” responses (Supplemental Figure 1), indicating improvement in patients’ psychological impact resulting from changes in their facial appearance. Eight out of 10 items that assessed the patients’ positive feelings about themselves (eg, feeling happy, comfortable, accepting, confident, etc) were associated with “somewhat agree” responses at baseline and “definitely agree” responses at the end of the study, whereas 2 items that assessed feeling attractive and feeling great remained unchanged at “somewhat agree” (Supplemental Figure 1). For all items on the scale, 58.6% to 89.7% of the patients somewhat or definitely agreed with the statements at baseline compared with 91.4% to 100% at the end of the study.
On average, most of the baseline scores on the Social Function Scale were associated with “somewhat agree” responses, whereas most mean scores at the end of the study were associated with “definitely agree” responses (Supplemental Figure 2), indicating improvement in patients’ social function resulting from changes in their facial appearance. Five out of 8 items, including those that assessed positive interactions with people (eg, making a good impression, feeling confident and comfortable), were associated with “somewhat agree” responses at baseline and “definitely agree” responses at the end of the study, whereas 3 items that assessed feeling confident in new social situations, feeling relaxed around unfamiliar people, and feeling confident when walking into a room with new people remained unchanged at “somewhat agree” (Supplemental Figure 2). For all items on the scale, 56.9% to 86.2% of the patients somewhat or definitely agreed with the statements at baseline compared with 91.4% to 100% at the end of the study.
On average, most of the baseline scores on the Satisfaction with Skin Scale were associated with “somewhat dissatisfied” responses, whereas most mean scores at the end of the study were associated with “somewhat satisfied” responses (Supplemental Figure 3), indicating improvement in patients’ complexion. Most (9/12) items on the scale, including those that assessed patient satisfaction with facial skin at the start and end of the day, appearance of health, attractiveness, smoothness, refreshed, hydration, radiance, tone, and skin tone evenness, were associated with “somewhat dissatisfied” responses at baseline and “somewhat satisfied” responses at the end of the study (Supplemental Figure 3). Satisfaction with facial skin clarity was associated with “somewhat dissatisfied” responses at baseline and “somewhat satisfied” and “very satisfied” responses at the end of the study. One item that assessed satisfaction with skin pores was associated with “very dissatisfied” responses at baseline and “somewhat satisfied” responses at the end of the study. For all items on the scale, 10.3% to 46.6% of the patients were somewhat or very satisfied at baseline compared with 55.2% to 91.4% by the end of the study.
On average, most of the baseline scores on the Aging Appraisal Scale were associated with “somewhat agree” responses, whereas most mean scores at the end of the study were associated with “somewhat disagree” or “definitely disagree” responses, indicating improvement or a more favorable assessment of how old patients look (Supplemental Figure 4). Six out of 7 items were associated with “somewhat agree” responses at baseline; of these items (3/6) assessing how worried the patients are by how old they look, looking older than desired in recent photographs and being reminded of how old they looked when seeing their reflection were associated with “somewhat disagree” at the end of the study. The remaining items (3/6), including the patients not looking like themselves in the mirror, being bothered by how old they look, and perceiving themselves as looking older than they wish to, were associated with “definitely disagree” at the end of the study (Supplemental Figure 4). Only 1 item that assessed if looking old impacted the ability of the patients to recognize themselves remained unchanged at “definitely disagree” both at baseline and at the end of the study. For all items on the scale, 15.5% to 55.2% of the patients somewhat or definitely disagreed with the statements at baseline compared with 70.7% to 93.1% at the end of the study.
Global Aesthetic Improvement Scale (GAIS)
Investigators rated patients’ facial appearance as “much improved” (91%) or “improved” (9%) after treatment. Most (98%) patients reported improvement in their facial appearance after treatment (“much improved,” 76%; “improved,” 22%), with 2% reporting “no change.”
Periorbital Aesthetic Appearance Questionnaire (PAAQ)
At the final study visit, the mean PAAQ total score improved significantly (P < .0001) from baseline by 32.6. Mean transformed scores also improved significantly from baseline to the final visit for each of the 3 PAAQ domains (P < .0001 for each domain). PAAQ scores improved by 32.0 for the psychological domain, 37.4 for the appearance domain, and 21.6 for the coping domain.
Safety
Half (50%) of the patients experienced at least 1 treatment-emergent AE (Table 3). Most were mild to moderate in severity. Edema and headache were the most-reported treatment-emergent AEs (incidence of 6.9% for each). Other treatment-emergent AEs that occurred in >1 patient were pain (5.2%), dysaesthesia (5.2%), contusion (5.2%), injection-site reaction (3.4%), nodule (3.4%), urinary tract infection (3.4%), and swelling face (3.4%). All treatment-emergent AEs resolved spontaneously. There were no deaths, serious treatment-emergent AEs, or treatment-emergent AEs leading to study discontinuation.
Table 3.
Treatment-Emergent Adverse Events by Treatment Type
| Parameters | ATX-101, n (%) (n = 13) | Non-ATX-101, n (%) (n = 45) | Patients, n (%) (N = 58) |
|---|---|---|---|
| All treatment-emergent AEs | 9 (69.2) | 20 (44.4) | 29 (50) |
| Severe treatment-emergent AEs | 3 (23.1) | 0 (0.0) | 3 (5.2) |
| Procedure-related AEs | 3 (23.1) | 5 (11.1) | 8 (13.8) |
| Product-related AEs | |||
| ATX-101 | 7 (53.8) | 0 (0.0) | 7 (12.1) |
| OnabotulinumtoxinA | 0 (0.0) | 5 (11.1) | 5 (8.6) |
| VYC-12L | 0 (0.0) | 1 (2.2) | 1 (1.7) |
| VYC-15L | 1 (7.7) | 3 (6.7) | 4 (6.9) |
| VYC-17.5L | 0 (0.0) | 2 (4.4) | 2 (3.4) |
| VYC-20L | 0 (0.0) | 5 (11.1) | 5 (8.6) |
| Skincare products | 0 (0.0) | 2 (4.4) | 2 (3.4) |
AE, adverse event.
Most (94.8%) patients reported ISRs, and most were mild to moderate in severity (Figure 5). The most common (≥75% of all patients) ISRs were tenderness, firmness, swelling, lumps, and bruising. The mean time to resolution was <14 days (Table 4).
Figure 5.
Incidence and severity of injection-site responses (ISRs).
Table 4.
Duration of Injection-Site Responses (N = 58)
| Patients, n (%) | Mean duration, days (median; range) | |
|---|---|---|
| Redness | 43 (74.1) | 5.1 (3.0; 1-30) |
| Pain | 38 (65.5) | 5.9 (2.5; 1-35) |
| Tenderness | 54 (93.1) | 8.7 (7.5; 1-30) |
| Firmness | 50 (86.2) | 9.1 (6.5; 1-33) |
| Swelling | 53 (91.4) | 6.8 (4.0; 1-36) |
| Lumps | 50 (86.2) | 13.6 (8.5; 1-52) |
| Bruising | 50 (86.2) | 8.7 (7.0; 1-29) |
| Itching | 26 (44.8) | 3.9 (1.0; 1-14) |
| Discoloration | 30 (51.7) | 7.0 (5.5; 1-22) |
| Other | 19 (32.8) | 7.5 (3.0; 1-52) |
DISCUSSION
Age-dependent changes in specific facial areas can contribute to deficits in other facial areas.16 The current trend in the aesthetics field involves global, comprehensive, and multimodal treatment approaches that consider the interrelationship between different facial areas and the submental area.9,16,17 Therefore, systematic, well-designed studies, where the authors evaluate this treatment approach, are useful to inform clinical practice. The Canada HARMONY study utilized a comprehensive, multimodal aesthetic treatment approach, which included treatment of the face with HA fillers and onabotulinumtoxinA and treatment of the submental area with ATX-101, along with a daily skincare regimen of medical-grade skincare products. This study demonstrated that patients were satisfied with their appearance after treatment when assessed using validated patient-reported outcome measures.
The panfacial approach used in this study was successful as assessed by validated patient-reported measures, including 5 FACE-Q Scales and GAIS, which are widely used in aesthetic studies, including the US HARMONY study.9,13 In the current study, patients reported significant improvement from baseline to the final study visit on the FACE-Q Satisfaction with Facial Appearance Scale score, the primary endpoint. There was a pronounced shift for every individual question in the proportion of patients who were initially dissatisfied at baseline and then subsequently became somewhat or very satisfied by the end of the study.
Panfacial multimodal treatment positively impacted appearance, patient well-being, and perceptions of age. Most patients and all investigators rated facial appearance as “much improved” or “improved” after treatment on the GAIS. At the end of the study, over 90% of patients somewhat or definitely agreed with items on the FACE-Q Psychological Function Scale, indicating positive feelings about themselves. Changes from baseline to final study visit on the PAAQ also demonstrated significant improvements, as reflected by the PAAQ total score and the individual scores for each domain (psychological, appearance, and coping domains). These results highlight how the panfacial treatment approach can positively impact the appearance of specific facial regions, such as the periorbital area, which in turn affects patient well-being.
Similar benefits of a panfacial approach were demonstrated in the US HARMONY study, such as improved patient satisfaction.9,13 On average, baseline scores for most patients were associated with “somewhat dissatisfied” or “somewhat satisfied” responses, and the scores 4 months posttreatment were associated with “somewhat satisfied” or “very satisfied” responses, indicating improvement or satisfaction with their facial appearance after treatment.9 The current study builds on the US HARMONY study and extends the panfacial approach. Unlike the US study, which combined treatment with HA fillers, onabotulinumtoxinA, and bimatoprost for treatment of eyelash hypertrichosis, Canada HARMONY included ATX-101 treatment, which addresses SMF, and a daily skincare regimen along with HA fillers and onabotulinumtoxinA.
The submental area is an important area of concern for both males and females. In a 2019 survey, 73% of 3645 consumers responded that they were bothered by excess fat under the chin.18 In a survey of 600 males aged 30 to 65 years who were aesthetically oriented but naive to injectable treatment, 70% responded that a double chin was an area of concern that they would prioritize for aesthetic treatment.19 An online survey of 603 females aged 30 to 65 years who were considering aesthetic treatments found that the chin was an area by which a proportion were somewhat or very bothered, and 24% responded that they would prioritize the chin area for treatment.20 Previous studies have demonstrated the safety and efficacy of ATX-101,21-25 including long-term efficacy.26 Therefore, including treatment of the submental area in the panfacial approach to aesthetic treatment addresses another important area of concern. Minimally invasive techniques for SMF reduction, such as the use of ATX-101, have become increasingly popular because they require less recovery time and can be used as part of a multimodal approach.27
Facial skin issues (texture, uneven skin tone, acne, and redness) are also important aesthetic concerns for patients. In a multicountry survey of 14,584 aesthetically conscious adults (30% males, 70% females) and 1315 aesthetic physicians, patients, but not physicians, rated facial skin issues as one of their extreme or high aesthetic concerns.28 Incorporating daily treatment with medical-grade skincare products in the panfacial approach addresses this aesthetic concern, which may be underestimated by many physicians. The use of skincare products is an important supplement to injectable treatments. Studies showed benefits of the addition of skincare regimens to HA filler and botulinum toxin A panfacial treatment.1,29 Improvements in skin quality, facial appearance, satisfaction, self-esteem, and first impressions by observers were reported. However, these studies included fewer than 20 females each.
Similar to the US HARMONY study, the combination of treatments in the current study was safe, with no treatment-emergent AEs that were serious or that led to study discontinuation.3-8 The severity and duration of ISRs in both studies were mild to moderate and had a mean duration of <14 days.9 The safety profile was similar to that of the individual treatments.
The current study had some limitations. This was a nonrandomized study and consisted of a single arm (no comparator) that did not include objective assessments of aging and/or skin quality. Most of the patients were female, limiting the generalizability of the results, and >90% of patients had Fitzpatrick skin phototypes II and III, limiting the diversity of the population. Regarding the use of skincare products, patient use of these products was optional, which may have negatively affected compliance, and the impact of skincare products was not specifically evaluated. Only a small subset of patients received ATX-101 treatment (n = 13), thus limiting meaningful comparative analysis between the groups of patients who received and did not receive ATX-101. Another limitation of the current study was limited in-person investigator assessments because of the COVID-19 pandemic. There may also be inherent bias in self-reporting instruments,9,30,31 especially because patients were not blinded to treatment. However, blinding patients may not be possible given the multimodal treatment approach because treatment is customized to the patients’ individual needs.9 Except for the investigator-rated GAIS, in the Canada HARMONY study, the authors did not include investigator-reported outcomes, which may complement the positive results from the patient-reported outcomes. Unlike the current study, the US HARMONY study included blinded investigator-rated assessments using photonumeric rating scales that demonstrated improvements in appearance, as well as the severity of lines/folds.9
CONCLUSIONS
The Canada HARMONY study represents a comprehensive investigation of the outcomes of a panfacial approach to aesthetic treatment. The study extends and supports the findings of the US HARMONY study, with results showing that multimodal, minimally invasive aesthetic treatments to the face and submental areas led to considerable improvements in patient-reported satisfaction with facial appearance, psychological function, social function, and aging appraisal on validated patient-reported outcomes scales. Treatments were well tolerated, with no serious treatment-emergent AEs reported.
Supplemental Material
This article contains supplemental material located online at https://doi.org/10.1093/asjof/ojae130.
Supplementary Material
Acknowledgments
AbbVie (Irvine, CA) and the authors thank all the trial investigators and the patients who participated in this clinical trial. The clinical trial data associated with this article can be requested online by qualified researchers through Vivli (Burlington, MA) following review and approval of a research proposal, statistical analysis plan, and execution of a data sharing agreement. The data will be accessible for 12 months.
Disclosures
Medical writing support was provided by Maria Ali, PhD and Maria Lim, PhD of Peloton Advantage, LLC (an OPEN Health company, London, UK) and funded by Allergan Aesthetics, an AbbVie Company (Irvine, CA). Dr Bertucci is a speaker, investigator, and consultant for Allergan Aesthetics, an AbbVie Company; speaker, investigator, and/or consultant for Evolus (Newport Beach, CA), Galderma (Lausanne, Switzerland), Merz (Raleigh, NC), Prollenium (Richmond Hill, Canada), Revance Therapeutics (Nashville, TN), and Teoxane (Geneva, Switzerland). Dr Carruthers is a consultant and researcher for Allergan Aesthetics, an AbbVie Company, Alastin (Carlsbad, CA) Appiell (Richardson, TX), Avari (Vancouver, BC), Bonti (Newport Beach, CA; now with Allergan/AbbVie), Evolus, Fount Bio (Cambridge, MA), In Mode (Irvine, CA), Inverse Genomics, Ltd, Jeune Aesthetics (Pittsburgh, PA), Merz, Revance Therapeutics, Object Pharma (Aliso Viejo, CA), and Sofwave Medical (Yokne'am Illit, Israel). Dr Humphrey is a speaker, investigator, and/or consultant for Allergan Aesthetics, an AbbVie Company, Galderma, Merz, and Revance Therapeutics. Dr McGillivray is a speaker, investigator, and consultant for Allergan Aesthetics, an AbbVie Company, and an investigator for Galderma and Medytox (Seoul, South Korea). Dr Muhn is a speaker, investigator, and/or consultant for Allergan Aesthetics, an AbbVie Company, Galderma, Medytox, Merz, and Revance Therapeutics. Dr Rivers is an investigator, speaker, and consultant for Allergan Aesthetics, an AbbVie Company, and an investigator for Galderma and Medytox. Dr Solish is an investigator/researcher for and honorarium recipient from Allergan Aesthetics, an AbbVie Company, Galderma, Merz, and Revance Therapeutics. Drs Bhogal, Garcia, Sangha, and Manson Brown are full-time employees of AbbVie.
Funding
Allergan Aesthetics, an AbbVie Company (Irvine, CA), funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication.
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