Abstract
Juvéderm Vollure XC (VYC-17.5L; Allergan plc, Dublin, Ireland) belongs to a family of hyaluronic acid gels based on the Vycross technology platform.
The authors sought to evaluate the safety and effectiveness of Vollure for correction of moderate to severe nasolabial folds (NLFs) over 18 months and after repeat treatment.
In this prospective, randomized study, patients (N = 123) received initial/touch-up treatment with Vollure in 1 NLF and control filler in the contralateral NLF. Patients received optional repeat treatment with Vollure after month 12, 15, or 18. Assessments included investigator-rated NLF Severity Scale responder rates (≥1-point improvement vs baseline), patient-assessed Appraisal of Nasolabial Folds scale of the FACE-Q questionnaire, and patient satisfaction (11-point scale).
Median volume of Vollure injected was 1.7 mL for initial/touch-up treatment combined and 0.6 mL for repeat treatment. The NLF Severity Scale responder rates were 93%, 85%, and 59% at months 6, 9, and 18 after initial/touch-up treatment and increased to 94% at 1 month after repeat treatment. Mean patient-reported FACE-Q scores significantly improved from baseline at all timepoints. Most patients were very satisfied with treatment at all timepoints from day 3 (75%) through month 18 (68%) and at 1 month after repeat treatment (94%). Common injection site responses after initial/touch-up and repeat treatment were firmness, swelling, and tenderness to touch; most were mild/moderate.
Vollure was safe and effective for correction of moderate to severe NLFs, with results lasting 18 months in 59% of NLFs. Repeat treatment required one-third of the injection volume to achieve similar improvement in NLF severity as initial/touch-up treatment.
Nasolabial folds (NLFs) are deep wrinkles running from the side of the nose to the corner of the mouth that are caused by a combination of factors, including migration of midfacial fat compartments, changes in muscle contour, and sagging skin.1,-3 These “smile lines” may appear in young adulthood, and the prevalence has been reported to be as high as 85% by age 40 to 49 years.4,5 Correction of NLFs can be accomplished utilizing injectable hyaluronic acid (HA) gels to provide volume and restore the natural 3-dimensional contour of the area.6,7
Juvéderm Vollure XC (Vollure [VYC-17.5L]; Allergan plc, Dublin, Ireland) belongs to a family of highly moldable HA gels based on the Vycross technology platform (Allergan plc), which combines low– and high–molecular-weight HA to improve the crosslinking efficiency of the HA chains.8,9 The tightly crosslinked HA network yields a gel with performance features that include lift capacity, moldability, tissue integration, and response durability.8,10 Lidocaine is included in the Vollure formulation to increase the comfort of the patient and reduce the need for conventional anesthetics during the procedure.8,11
The present study evaluated the safety and effectiveness of Vollure for treatment of moderate to severe NLFs. The study met the 6-month co-primary endpoints, showing that the effects of Vollure were noninferior to those of the control HA filler and that the Vollure responder rate was significantly greater than 50% at month 6 (P < 0.001).9 This report presents safety and effectiveness results for Vollure through 18 months after treatment and at 1 month after repeat treatment.
METHODS
Study Design and Treatment
Six investigational sites in the United States participated in this prospective, multicenter, randomized, within-patient controlled study (clinicaltrials.gov identifier NCT01976663). Each site had an unblinded treating investigator (TI) and a blinded evaluating investigator (EI). The study was conducted in compliance with Good Clinical Practice guidelines. A central institutional review board (Quorum Review, Inc., Seattle, WA) covering all investigational sites approved the protocol before any patients were enrolled. All patients provided written informed consent. The study began enrolling patients in October 2013 and was completed in October 2015.
The study design and patient eligibility criteria have been previously described.9 Briefly, the study enrolled adults (aged ≥18 years) with severity scores of 2 (moderate) or 3 (severe) for both NLFs on the validated, 5-point photonumeric NLF Severity Scale (NLFSS) (Figure 1). Eligible patients were randomized to initial treatment with Vollure in either the right or left NLF and control in the contralateral NLF. Randomization was based on a central randomization schedule stratified by investigational site utilizing an automated interactive voice response system accessed by the TI or study coordinator. Data from NLFs initially randomized to the Vollure treatment arm are reported here.
The Allergan NLF Severity Scale. Printed with permission from Allergan plc.
The study comprised initial treatment; an optional touch-up treatment at 30 days later if judged necessary by the TI; optional asymmetry correction administered after month 9, 12, or 15; and repeat treatment administered after the month 12, 15, or 18 visit.
Asymmetry Correction
Within 4 weeks after the month 9, 12, and 15 visits, patients were eligible to request a single, unilateral treatment to correct clinically significant asymmetry (at least 1-point difference in EI-assessed NLFSS score between NLFs). The TIs conducted asymmetry correction using Vollure injected into the more severe NLF only, regardless of initial treatment group for that NLF.
Repeat Treatment
Within 4 weeks after the month 12 or 15 visits, patients were eligible to receive repeat treatment if the NLFSS for both NLFs had returned to baseline or worse, based on the EI’s live assessment. Alternatively, patients were eligible to receive repeat treatment if they had received asymmetry correction in 1 NLF at a previous visit and also had clinically significant asymmetry (at least 1-point difference in NLFSS score between NLFs), with the contralateral NLF being more severe. All patients who did not receive repeat treatment before the month 18 visit received repeat treatment at that time regardless of NLF severity score. For repeat treatment, the TI injected Vollure into one or both NLFs. Patients who chose not to receive repeat treatment at month 18 were discontinued from the study. Patients exited the study after completion of the month 1 visit after repeat treatment.
Patients and EIs remained blinded to the treatment assignment for each NLF throughout the study duration. The total study duration was up to 20 months (1 month for treatment and up to 19 months of follow-up).
Assessments
Routine follow-up visits for assessment of effectiveness and safety occurred at 3 and 14 days following each treatment; at 1, 3, 6, 9, 12, 15, and 18 months after the initial treatment (or after the touch-up treatment, if touch-up was performed); and at 1 month after repeat treatment. The EIs evaluated NLF severity employing the NLFSS (0 = none; 1 = mild; 2 = moderate; 3 = severe; 4 = extreme) at screening; at 1, 3, 6, 9, 12, 15, and 18 months after the initial/touch-up treatment; and at 1 month after repeat treatment. Patients rated satisfaction with treatment for each NLF utilizing an 11-point scale (0 = completely dissatisfied; 10 = completely satisfied) at all follow-up visits. In addition, patients completed the Appraisal of Nasolabial Folds scale of the FACE-Q12 at screening and at months 3, 6, 12, and 18 after initial/touch-up treatment. Patients were identified by name on the front cover of the set of patient-reported outcomes for each visit, but names were not provided on the individual assessment pages within each package.
After each treatment, patients completed a 30-day safety diary with a checklist of 9 common injection site responses (ISRs). Patients recorded the severity of ISRs in the safety diary as mild, moderate, or severe. ISRs that were ongoing at the end of the diary entries were automatically considered to be adverse events (AEs).
Statistics
Effectiveness analyses were conducted on the modified intent-to-treat population, which included all randomized patients who received study treatment. The responder rate, based on the EI’s live assessments of NLF severity on the NLFSS, was defined as the percentage of NLFs that showed ≥1-point improvement (ie, decrease in severity) from baseline. Any NLF that received asymmetry correction or repeat treatment prior to the visit was defined as a nonresponder for that visit. An observed responder rate of at least 50% at 12 months indicated that the product lasted for at least 12 months. Patient responses to the 5 FACE-Q items were combined into an overall score ranging from 0 (patient is extremely bothered by appearance of the NLF) to 100 (patient is not at all bothered by the appearance of the NLF) utilizing the scoring algorithm from the scale developers. Means and 95% confidence intervals (CIs) for overall FACE-Q scores were calculated for each timepoint; lack of overlap between 95% CIs for posttreatment vs baseline mean scores indicated a significant difference from baseline. The percentage of patients reporting moderate or extreme bother was calculated for each of the 5 FACE-Q items. For NLFs that received asymmetry correction or repeat treatment prior to the visit, the last-observation-carried-forward score on the FACE-Q for that NLF was utilized for future visits. Other effectiveness endpoints and safety parameters were analyzed descriptively.
RESULTS
Patient Disposition
Of the 126 patients enrolled, 123 patients received initial treatment, 63 patients received touch-up treatment with Vollure (n = 50) or control HA filler (n = 59; not all patients had touch-up in both NLFs), 45 received asymmetry correction with Vollure, and 85 received repeat treatment with Vollure at month 12 (n = 9), month 15 (n = 14), or month 18 (n = 62) (Figure 2). Patients who were eligible for asymmetry correction but opted not to receive asymmetry treatment did so most commonly because they were satisfied with current results. Most (72.9%) of the patients who received repeat treatment did not need or request repeat treatment until the month 18 visit. Eighty-four patients completed the study (ie, received initial treatment and repeat treatment and completed the final study visit). Twenty-four patients (19.0%) completed follow-up through 18 months but did not receive repeat treatment and were therefore considered noncompleters. Figure 2 shows reasons for not receiving repeat treatment.
Patient disposition. aRegarding patients who did not receive asymmetry correction, reasons were not recorded for all. bThe most common reasons for not completing the study were those categorized as “other” for 24 patients (19.0%), all of whom completed follow-up through month 18 but elected to not receive repeat treatment. Reasons for not receiving treatment are summarized within the repeat treatment box.
Patient Characteristics and Treatment Administration
The demographic characteristics and baseline characteristics of the study population have been published.9 Briefly, most patients were female (95.1%, 117/123) and white (74.0%, 91/123). The median age was 54.0 years (range, 33-83 years). All Fitzpatrick skin types were well represented. Mean baseline NLFSS score was 2.6, consistent with the enrollment criteria of moderate or severe NLFs.
In preparation for each treatment, most patients received anesthesia (most commonly topical). For initial treatment, 82.2% of patients received topical anesthesia. Among patients receiving repeat treatment, 78.8% received anesthesia (topical, 77.6%; ice, 1.2%; local anesthesia, 1.2%). The mean duration for topical anesthesia for repeat treatment was 33 minutes.
The median volume injected was 1.7 mL for initial and touch-up treatment combined and 0.6 mL for repeat treatment (Table 1). Serial puncture was the most common injection technique.
Treatment Administration for NLFs Treated with Vollure
| Parameter | Initial and touch-up treatment | Repeat treatment |
|---|---|---|
| n = 123 | n = 85 | |
| Volume injected per NLF, median (range), mL | Total: 1.7 (0.1-3.0) Initial: 1.4 (0.1-3.0) Touch-up: 0.7 (0.1-1.0)a | 0.6 (0.0-1.5) |
| Injection technique used, n (%)b | ||
| Serial puncture | 114 (92.7) | 66 (77.6) |
| Tunneling | 62 (50.4) | 34 (40.0) |
| Fanning | 39 (31.7) | 26 (30.6) |
| Cross-hatching | 20 (16.3) | 8 (9.4) |
| Parameter | Initial and touch-up treatment | Repeat treatment |
|---|---|---|
| n = 123 | n = 85 | |
| Volume injected per NLF, median (range), mL | Total: 1.7 (0.1-3.0) Initial: 1.4 (0.1-3.0) Touch-up: 0.7 (0.1-1.0)a | 0.6 (0.0-1.5) |
| Injection technique used, n (%)b | ||
| Serial puncture | 114 (92.7) | 66 (77.6) |
| Tunneling | 62 (50.4) | 34 (40.0) |
| Fanning | 39 (31.7) | 26 (30.6) |
| Cross-hatching | 20 (16.3) | 8 (9.4) |
NLF, nasolabial fold. aIn 50 patients, NLFs initially treated with Vollure had touch-up treatment with Vollure. bPatients may have received more than one injection technique.
Treatment Administration for NLFs Treated with Vollure
| Parameter | Initial and touch-up treatment | Repeat treatment |
|---|---|---|
| n = 123 | n = 85 | |
| Volume injected per NLF, median (range), mL | Total: 1.7 (0.1-3.0) Initial: 1.4 (0.1-3.0) Touch-up: 0.7 (0.1-1.0)a | 0.6 (0.0-1.5) |
| Injection technique used, n (%)b | ||
| Serial puncture | 114 (92.7) | 66 (77.6) |
| Tunneling | 62 (50.4) | 34 (40.0) |
| Fanning | 39 (31.7) | 26 (30.6) |
| Cross-hatching | 20 (16.3) | 8 (9.4) |
| Parameter | Initial and touch-up treatment | Repeat treatment |
|---|---|---|
| n = 123 | n = 85 | |
| Volume injected per NLF, median (range), mL | Total: 1.7 (0.1-3.0) Initial: 1.4 (0.1-3.0) Touch-up: 0.7 (0.1-1.0)a | 0.6 (0.0-1.5) |
| Injection technique used, n (%)b | ||
| Serial puncture | 114 (92.7) | 66 (77.6) |
| Tunneling | 62 (50.4) | 34 (40.0) |
| Fanning | 39 (31.7) | 26 (30.6) |
| Cross-hatching | 20 (16.3) | 8 (9.4) |
NLF, nasolabial fold. aIn 50 patients, NLFs initially treated with Vollure had touch-up treatment with Vollure. bPatients may have received more than one injection technique.
Effectiveness Investigator-Reported Outcomes
The NLFSS responder rate exceeded 90% through month 6, was 85% at month 9, decreased to 59% at month 18, and increased to 94% at 1 month after repeat treatment (Figure 3). The mean (SD) decrease (improvement) in NLFSS score from baseline at 1 month after initial treatment was 1.6 (0.8) points compared with an improvement of 1.7 (0.7) points 1 month after repeat treatment. Figures 4 and 5 show photographs representative of the treatment effect through repeat treatment and the treatment effect at month 18 without repeat treatment, respectively.
Nasolabial Fold Severity Scale (NLFSS) responder rates based on evaluating investigators’ assessments after treatment with Vollure. NLFs, nasolabial folds. aMonth 1R designates the responder rate at 1 month following repeat treatment with Vollure.
Representative photographs of this 60-year-old female patient’s right nasolabial fold at (A) baseline (EI rating severe), (B) month 6 (EI rating mild), and (C) month 18 (EI rating mild) after initial treatment and (D) 1 month following repeat treatment with Vollure (EI rating mild). The injection volume for the right nasolabial fold was 1.7 mL for initial treatment and 0.35 mL for repeat treatment. EI, evaluating investigator.
Representative photographs of this 60-year-old female patient’s left nasolabial fold at (A) baseline (EI rating severe) and (B) month 18 after treatment with Vollure (EI rating moderate). The total volume of Vollure injected into the left nasolabial fold was 1.5 mL. The patient did not receive touch-up or repeat treatment. EI, evaluating investigator.
Patient-Reported Outcomes
Improvement in FACE-Q scores over 18 months vs baseline showed continued benefit of Vollure from the patient perspective. Mean overall scores were 128%, 81%, and 56% higher than baseline at months 6, 12, and 18, respectively, and were significantly higher (95% CIs did not overlap) than baseline at all timepoints through 18 months (Figure 6A). Durable improvement after treatment was shown in each of the 5 questions of the FACE-Q (Figure 6B). For example, the percentage of patients reporting that they were moderately or extremely bothered by the depth of their NLFs (FACE-Q Question 1) decreased from 87.0% (107/123) at baseline to 13.7% (16/117) at month 6.
Appraisal of nasolabial fold (NLF) FACE-Q scores after treatment with Vollure by study visit. (A) mean overall score and (B) percentage of patients reporting that they were moderately or extremely bothered for each FACE-Q item. aResponses to 5 FACE-Q questions were combined into an overall nasolabial fold score ranging from 0 (extremely bothered by nasolabial fold) to 100 (not at all bothered). If NLF was treated for asymmetry correction, then the last observation carried forward score on the Appraisal of Nasolabial Folds scale for that nasolabial fold was used for future visits. bBaseline: n = 122 for question 3. cMonth 6: n = 116 for question 3. dMonth 12: n = 111 for questions 2, 4, and 5. CI, confidence interval.
Patients reported a high level of satisfaction with Vollure throughout the study (Figure 7). The percentage of patients who were very satisfied (score of 7-10 on an 11-point scale; 0 = completely dissatisfied,10 = completely satisfied) with treatment was 82% at month 6, exceeded 75% at all timepoints from month 6 to month 15, and increased to 94% at 1 month after repeat treatment.
Patient satisfaction with Vollure treatment of nasolabial folds. aPatients whose responses were in the 7 to 10 category on an 11-point scale (0 = completely dissatisfied, 10 = completely satisfied). bPatient satisfaction responses for nasolabial folds that received asymmetry correction at a prior visit were excluded from the analysis at months 12, 15, and 18, leading to a difference in the denominators at those timepoints. cMonth 1R designates the responder rate at 1 month following repeat treatment.
Safety
The incidence of ISRs after asymmetry correction and repeat treatment combined was lower than after initial treatment (Table 2). The proportion of patients who reported at least 1 ISR after Vollure treatment was 95.1% (116/122) after initial treatment and 79.1% (72/91) after asymmetry correction and/or repeat treatment. The most common ISRs after initial treatment and asymmetry/repeat treatment were firmness (88.5% and 69.2%, respectively), swelling (86.1% and 67.0%), and tenderness to touch (84.4% and 64.8%). Most ISRs were mild or moderate in severity, and the majority resolved within 2 weeks of initial treatment (66.4%, 77/116) and asymmetry/repeat treatment (54.2%, 39/72). In 1 patient, mild swelling not requiring treatment continued after the 30-day diary entries and was thus considered an AE. The patient remained in the study through the month 18 visit but declined repeat treatment.
Injection Site Responses After Initial Treatment and After Asymmetry Correction/Repeat Treatment Combined
| ISR, n (%) | Initial treatment | Asymmetry correction/repeat treatment |
|---|---|---|
| (n = 122)a | (n = 91)a | |
| Any ISR | 116 (95.1) | 72 (79.1) |
| Maximum severity | ||
| Mild | 22 (19.0) | 18 (25.0) |
| Moderate | 58 (50.0) | 29 (40.3) |
| Severe | 36 (31.0) | 25 (34.7) |
| ISR category | ||
| Firmness | 108 (88.5) | 63 (69.2) |
| Swelling | 105 (86.1) | 61 (67.0) |
| Tenderness to touch | 103 (84.4) | 59 (64.8) |
| Lumps/bumps | 100 (82.0) | 53 (58.2) |
| Redness | 90 (73.8) | 57 (62.6) |
| Pain after injection | 88 (72.1) | 48 (52.7) |
| Bruising | 69 (56.6) | 40 (44.0) |
| Itching | 38 (31.1) | 19 (20.9) |
| Discoloration | 33 (27.0) | 19 (20.9) |
| ISR, n (%) | Initial treatment | Asymmetry correction/repeat treatment |
|---|---|---|
| (n = 122)a | (n = 91)a | |
| Any ISR | 116 (95.1) | 72 (79.1) |
| Maximum severity | ||
| Mild | 22 (19.0) | 18 (25.0) |
| Moderate | 58 (50.0) | 29 (40.3) |
| Severe | 36 (31.0) | 25 (34.7) |
| ISR category | ||
| Firmness | 108 (88.5) | 63 (69.2) |
| Swelling | 105 (86.1) | 61 (67.0) |
| Tenderness to touch | 103 (84.4) | 59 (64.8) |
| Lumps/bumps | 100 (82.0) | 53 (58.2) |
| Redness | 90 (73.8) | 57 (62.6) |
| Pain after injection | 88 (72.1) | 48 (52.7) |
| Bruising | 69 (56.6) | 40 (44.0) |
| Itching | 38 (31.1) | 19 (20.9) |
| Discoloration | 33 (27.0) | 19 (20.9) |
ISR, injection site response. aNumber of patients who recorded in diaries after the specified treatment.
Injection Site Responses After Initial Treatment and After Asymmetry Correction/Repeat Treatment Combined
| ISR, n (%) | Initial treatment | Asymmetry correction/repeat treatment |
|---|---|---|
| (n = 122)a | (n = 91)a | |
| Any ISR | 116 (95.1) | 72 (79.1) |
| Maximum severity | ||
| Mild | 22 (19.0) | 18 (25.0) |
| Moderate | 58 (50.0) | 29 (40.3) |
| Severe | 36 (31.0) | 25 (34.7) |
| ISR category | ||
| Firmness | 108 (88.5) | 63 (69.2) |
| Swelling | 105 (86.1) | 61 (67.0) |
| Tenderness to touch | 103 (84.4) | 59 (64.8) |
| Lumps/bumps | 100 (82.0) | 53 (58.2) |
| Redness | 90 (73.8) | 57 (62.6) |
| Pain after injection | 88 (72.1) | 48 (52.7) |
| Bruising | 69 (56.6) | 40 (44.0) |
| Itching | 38 (31.1) | 19 (20.9) |
| Discoloration | 33 (27.0) | 19 (20.9) |
| ISR, n (%) | Initial treatment | Asymmetry correction/repeat treatment |
|---|---|---|
| (n = 122)a | (n = 91)a | |
| Any ISR | 116 (95.1) | 72 (79.1) |
| Maximum severity | ||
| Mild | 22 (19.0) | 18 (25.0) |
| Moderate | 58 (50.0) | 29 (40.3) |
| Severe | 36 (31.0) | 25 (34.7) |
| ISR category | ||
| Firmness | 108 (88.5) | 63 (69.2) |
| Swelling | 105 (86.1) | 61 (67.0) |
| Tenderness to touch | 103 (84.4) | 59 (64.8) |
| Lumps/bumps | 100 (82.0) | 53 (58.2) |
| Redness | 90 (73.8) | 57 (62.6) |
| Pain after injection | 88 (72.1) | 48 (52.7) |
| Bruising | 69 (56.6) | 40 (44.0) |
| Itching | 38 (31.1) | 19 (20.9) |
| Discoloration | 33 (27.0) | 19 (20.9) |
ISR, injection site response. aNumber of patients who recorded in diaries after the specified treatment.
The proportion of Vollure-treated NLFs at which AEs were reported was 23.6% (29/123) after initial/touch-up treatment and 10.8% (10/93) after asymmetry/repeat treatment. The most common AEs (>5% of patients for initial/touch-up or asymmetry/repeat treatment) were injection site induration (diary term: firmness, 10.6% and 7.5%, respectively), injection site mass (diary term: lumps/bumps, 7.3% and 3.2%), and injection site swelling (7.3% and 1.1%). Most AEs resolved within 60 days, and few required any treatment. Most AEs were mild or moderate; severe AEs were reported for 6 NLFs (4.9%) after initial/touch-up treatment and 4 NLFs (4.3%) after asymmetry/repeat treatment. All severe AEs resolved except for injection site induration and injection site mass in 1 patient following repeat treatment, which were still ongoing at the end of the 30-day follow-up period. There were 3 AEs that occurred weeks to months after the initial/touch-up treatment that required medication: mild swelling of the face after eating seafood, moderate skin mass, and severe itching. Swelling was treated with fexofenadine hydrochloride and ibuprofen, the skin mass was treated with triamcinolone cream, and the itching did not require treatment. All 3 events resolved without sequelae. No serious AEs or deaths related to treatment were reported. The AEs that did not occur at NLFs were typically events common in the general population (eg, nasopharyngitis, headache) and were generally not considered to be related to treatment.
DISCUSSION
Vollure was safe and effective for correcting moderate to severe NLFs, with improvements lasting through 18 months in 59% of NLFs. Repeat treatment with Vollure administered 12 to 18 months after initial/touch-up treatment required one-third of the injection volume and resulted in comparable improvement in NLF severity as initial/touch-up treatment (ie, >90% responders). Patients reported dramatic improvement in NLFs on the FACE-Q through 18 months and high levels of satisfaction with Vollure through 18 months and after repeat treatment. The safety profile of Vollure after asymmetry correction and repeat treatment was similar to that observed after initial treatment, although a lower proportion of patients experienced ISRs after asymmetry/repeat treatment compared with initial treatment.
The long-term safety and effectiveness profiles of Vollure were aligned with those reported for other Juvéderm HA-based dermal fillers for treatment of NLFs.13-19 In a 1-year prospective, open-label, postmarket study (N = 70), Vollure treatment significantly improved investigator-assessed NLF severity utilizing the NLFSS at 12 months vs baseline.8 Most studies of HA-based fillers for NLF correction have demonstrated effectiveness through 6 months after the initial/touch-up treatment,15,16,20-22 but few have evaluated maintenance of effectiveness at 1 year and beyond. In a blinded, split-face study (n = 81) of 2 HA fillers for treatment of moderate NLFs, responder rates (% patients with ≥1 grade improvement on the 5-point Wrinkle Severity Rating Scale) exceeded 90% at month 3, decreased to 50% to 60% at month 9 before repeat treatment, and increased to >80% and >70% at months 3 and 9 after repeat treatment; optional touch-up treatment was allowed 3 weeks after initial and repeat treatment.23 The volume of HA required for repeat treatment was approximately two-thirds of that required for initial/touch-up treatment. The current study, which is unique in evaluating effectiveness through 18 months after the initial/touch-up treatment, showed that Vollure maintained a 1-point or greater improvement in NLFSS score in 59% of NLFs at 18 months without repeat treatment. Most (73%) of the patients who received repeat treatment in the current study did not need or request repeat treatment until month 18, and the median volume required for repeat treatment was approximately one-third of that required for initial/touch-up treatment. The prolonged duration of response with Vollure suggests that repeat treatment will be required less frequently with Vollure than with other HA-based fillers.
Patient satisfaction was high throughout this 18-month study, consistent with patient satisfaction data reported in the 12-month, open-label, postmarket study of Vollure.8 In addition, patients reported significant improvements from baseline in the appearance of their NLFs on the FACE-Q at all timepoints through month 18. Most patients reported improvements in how old their NLFs made them look and their appearance compared with peers. Other studies have shown that correction of NLFs positively influences patients’ well-being, self-esteem, and projected first impressions, including improvements in perceptions of social skills and success.24-26
The results of this study are limited by the short duration of follow-up (1 month) after repeat treatment. Additional evaluations of safety and duration of effectiveness after repeat treatment are needed. The FACE-Q was not assessed after repeat treatment. Nonetheless, it is likely that FACE-Q scores would have returned to high levels after repeat treatment.
CONCLUSIONS
Vollure was safe and effective for long-term correction of moderate to severe NLFs, with improvements lasting through 18 months in 59% of patients. Repeat treatment with Vollure required one-third of the injection volume to achieve similar improvement in NLF severity as initial/touch-up treatment. Patients reported dramatic improvement in the appearance of their NLFs and were highly satisfied with Vollure treatment.
Acknowledgments
The authors express their appreciation to all treating and evaluating investigators who participated in this study and to Shraddha Mehta, PhD, of Allergan plc for conducting the statistical analyses. Treating investigators were Kenneth Beer, MD, PA (West Palm Beach, FL); Fredric Brandt, MD and Joely Kauffman-Janette, MD (Coral Gables, FL); Steven H. Dayan, MD (Chicago, IL); Pearl E. Grimes, MD (Los Angeles, CA); Gary Monheit, MD (Birmingham, AL); and Corey Maas, MD, FACS (San Francisco, CA). Evaluating investigators were Richard Schwartz, MD (West Palm Beach, FL); Christopher O’Connell, MD (Coral Gables, FL); Otto Placik, MD (Chicago, IL); Rajesh Chopra, MD, FACS (Los Angeles, CA); Melanie L. Appell, MD (Birmingham, AL); and Vic A. Narurkar, MD (San Francisco, CA).
Disclosures
Dr Dayan is a researcher, speaker, and consultant for Allergan plc. Dr Maas is a researcher, consultant, and advisory board member for Allergan plc. Dr Grimes is an investigator and advisory board member for Allergan plc; and is an investigator for Valeant and Galderma. Dr Beer is a clinical trial investigator, consultant, and speaker for Allergan plc, Galderma, and Merz; a shareholder in Anterios; and a partner in The Cosmetic Bootcamp and Theraplex LLC. Dr Monheit is a consultant and clinical investigator for Allergan plc, Revance, Galderma, Merz, and Suneva; and is a clinical investigator for Teoxane, Alphaeon, CROMA, Evolus, and Sienna Pharmaceuticals. Dr Snow is an employee of Allergan plc and may own stock in the company. Mr Murphy and Dr Lin are former employees of Allergan plc and were employed by Allergan plc at the time this study was conducted. The opinions expressed in this article are those of the authors. The authors received no honorarium or other form of financial support related to the development of this article.
Funding
This study was sponsored by Allergan plc (Dublin, Ireland). Writing and editorial support was provided by Lela Creutz, PhD, of Peloton Advantage, an OPEN Health company (Parsippany, NJ) and was funded by Allergan plc. Allergan plc designed the study and analyzed the data presented in this article.
REFERENCES
Author notes
Dr Dayan is the Medical Director, Principal Investigator, and Founder of DeNova Research in Chicago, IL.
Dr Maas is a plastic surgeon in private practice in San Francisco, CA.
Dr Grimes is a dermatologist in private practice in Los Angeles, CA.
Dr Beer is a dermatologist in private practice in West Palm Beach, FL.
Dr Monheit is a dermatologist in private practice in Birmingham, AL.
Dr Snow is the Director of Clinical Development at Allergan plc, Irvine, CA.
At the time of this study, Ms Murphy, MBA was the Director of Clinical Development and Dr Lin was the Associate Director of Clinical Development at Allergan plc, in Irvine, CA.
