Juvéderm Volbella with Lidocaine was less disruptive to daily activities versus Restylane-L based on the subject-reported FACE-Q Recovery Early Life Impact and Recovery Early Symptoms modules assessed on day 1. On the Recovery Early Life Impact module, the mean score was significantly higher with Juvéderm Volbella with Lidocaine versus Restylane-L (77.5 vs 69.6; between-group 95% CI, 3.6–12.1; P < 0.001) (Fig. 5). Similarly, on the Recovery Early Symptoms module, mean score was significantly higher for Juvéderm Volbella with Lidocaine (85.5 vs 73.4; between-group 95% CI, 8.4–16.0; P < 0.001). Subjects in the Juvéderm Volbella with Lidocaine group were significantly less bothered by discomfort, pain, swelling, tenderness, feeling sore, numbness, throbbing, and tingling versus the Restylane-L group (P < 0.001) on day 1 as assessed on individual items of the Recovery Early Symptoms module.
Subjects in the Juvéderm Volbella with Lidocaine group were significantly more satisfied with their lips and the outcomes of treatment at month 3 than subjects in the Restylane-L group (P = 0.015 and P = 0.031, respectively) based on the Satisfaction with Lips and Satisfaction with Outcome modules of the FACE-Q. Individual items of the Satisfaction with Lips module at month 3 showed that Juvéderm Volbella with Lidocaine subjects were significantly more satisfied than Restylane-L subjects with lip fullness (P = 0.010), natural look of lips (P = 0.023), softness of lips (P = 0.001), attractiveness of lips (P = 0.026), and overall look of lips (P = 0.038).
Mean changes in lip volume (0.68 mL vs 0.93 mL) and lip surface area (31% vs 38%) on day 1 were smaller with Juvéderm Volbella with Lidocaine versus Restylane-L. By day 14, mean change from baseline did not differ between treatments, likely reflecting less short-term swelling following treatment with Juvéderm Volbella with Lidocaine. At month 3, mean lip surface area had increased by 19% with Juvéderm Volbella with Lidocaine versus 13% with Restylane-L. Based on self-assessments, the percentage of subjects achieving treatment goal was similar between groups at month 1 but was numerically higher with Juvéderm Volbella with Lidocaine at month 3 (73.3% vs 62.2%; P = 0.0629) (Fig. 6).
Investigators assessed their overall satisfaction with the aesthetic features of the subject’s lips and mouth in repose and in animation. At month 3, investigators indicated that they were “very satisfied” with the aesthetic features in most subjects at repose (90.2% with Juvéderm Volbella with Lidocaine, 84.5% with Restylane-L; scores of 7–10 on the 0–10 scale were grouped to create a “very satisfied” category) (Fig. 7).
Most subjects reported ≥1 ISR, with swelling, tenderness, and firmness being the most frequently reported in both treatment groups (Table 4). Several ISR categories were reported significantly less frequently with Juvéderm Volbella with Lidocaine versus Restylane-L, including lumps/bumps, firmness, pain, itching, and discoloration. Moreover, subjects receiving Juvéderm Volbella with Lidocaine were less likely to report severe ISRs (32.0% vs 60.2%). More than twice as many subjects reported severe swelling after treatment with Restylane-L (49.2%) than with Juvéderm Volbella with Lidocaine (22.1%). Most ISRs lasted ≤14 days; 23.4% of subjects receiving Juvéderm Volbella with Lidocaine and 25.6% receiving Restylane-L had ISRs lasting for 15–30 days, most commonly lumps/bumps (22.3% vs 23.1%) and firmness (10.8% vs 10.9%). Swelling lasting 15–30 days was reported by 1 subject (0.8%) receiving Juvéderm Volbella with Lidocaine and 6 subjects (4.5%) receiving Restylane-L.
Device-related AEs were reported in 14 subjects (10.1%) receiving Juvéderm Volbella with Lidocaine versus 19 subjects (13.5%) receiving Restylane-L; all occurred at the injection site. The Juvéderm Volbella with Lidocaine group had 22 device-related AEs, all mild or moderate in severity, with the most frequent being lumps/bumps (n = 11) and firmness (n = 4). In comparison, the Restylane-L group had 55 device-related AEs, including 18 that were severe. The most frequent events were injection site pain (n = 17), lumps/bumps (n = 12), paresthesia (n = 9), and firmness (n = 5). For both treatment groups, lip sensitivity and speech pronunciation were not affected by treatment.
This study met its primary endpoint: the effectiveness of Juvéderm Volbella with Lidocaine for lip enhancement was noninferior to treatment with Restylane-L. The analysis was based on a subjective assessment by the ICR of overall lip fullness from 3D images using the LFS. Results were supported by subjective assessments made by investigators and subjects and by objective measurements of lip volume and surface area from analysis of the 3D images. Besides improving overall lip fullness, Juvéderm Volbella with Lidocaine was at least as effective as Restylane-L for improving perioral lines and oral commissures, including fine lines and wrinkles in the perioral region. In the investigator assessment, a significantly greater percentage of subjects receiving Juvéderm Volbella with Lidocaine achieved improvements in perioral lines and oral commissures at month 3 versus Restylane-L. These results agree with studies using other injectable gels from the Juvéderm family, including Juvéderm Volbella (without lidocaine) and Juvéderm Ultra, which were effective in augmenting lip fullness and reducing perioral lines and oral commissures.7,12 Juvéderm Volbella with Lidocaine was also shown to be effective in the correction of tear troughs and sunken eyes in the periocular area.13
Subjects receiving Juvéderm Volbella with Lidocaine reported better outcomes on day 1 than those receiving Restylane-L. This was evidenced by higher scores on the FACE-Q Recovery Early Life Impact and Recovery Early Symptoms modules, indicative of less disruption of normal daily activities. Lip volume measurements on day 1 support these findings. Subjects receiving Juvéderm Volbella with Lidocaine had a smaller mean change from baseline in lip volume on day 1 compared with those receiving Restylane-L, suggesting less acute, short-term swelling. At month 3, subjects reported greater satisfaction with Juvéderm Volbella with Lidocaine versus Restylane-L on the FACE-Q. Although investigators evaluated satisfaction based on the aesthetic features at 3 months after treatment, subjects evaluated satisfaction based on aesthetic features and other factors, indicating that patient satisfaction is a multidimensional concept.
The responder rate for overall lip fullness in both treatment groups, based on ICR assessment, was surprisingly low, particularly compared with a recent lip augmentation study conducted in the United States with a Restylane formulation without lidocaine.14 However, the injection volume for upper and lower lips was >2-fold higher in the Restylane study, possibly reflecting cultural differences between European and American ideals of lip enhancement. In the present study, investigators enrolled subjects who had minimal or mild baseline LFS scores, and the primary endpoint was based on LFS assessments made by the ICR from 3D images. The ICR and investigator assessments of LFS at baseline differed considerably; the ICR assessment found a higher mean LFS score and rated >50% of the subjects as having moderate or marked lip fullness at baseline. Accordingly, these subjects had little room to show the 1-point improvement in overall lip fullness necessary for classification as a responder. Differences were also observed between assessors for oral commissures and perioral lines. Together, these data suggest that photographs may present less detail and therefore are less sensitive for measuring observable changes compared with in-person assessment. In the Restylane study, responder rates were notably lower when based on assessments from photographs compared with live evaluations.14 In the present study, the month 3 responder rates based on the investigator assessments (84.2% with Juvéderm Volbella with Lidocaine and 81.4% with Restylane-L) suggest a much better outcome compared with the ICR assessments.
The overall incidence of subject-reported ISRs and device-related AEs was similar between treatment groups and consistent with expectations for hyaluronic acid dermal fillers. However, ISR severity was generally lower with Juvéderm Volbella with Lidocaine, and several types of ISRs, including lumps/bumps and firmness, were reported less frequently with Juvéderm Volbella with Lidocaine.
Two study limitations are notable. First, subjects were enrolled based on in-person assessment of lip fullness by investigators, whereas the primary analysis of treatment effectiveness depended on ICR assessment of 3D images. This contributed to differences in responder rate depending on the assessor. Regardless of the assessor, Juvéderm Volbella with Lidocaine was at least as effective as Restylane-L. Second, investigators were not blinded to the treatment assignment; consequently, they may have been biased in their assessments. However, qualitatively similar findings were obtained by the ICR and subjects themselves, who were blinded to treatment assignment.
This study demonstrates that Juvéderm Volbella with Lidocaine is safe and effective for aesthetic lip augmentation and improvement in perioral lines and oral commissures. Juvéderm Volbella with Lidocaine displayed a favorable risk-benefit profile for volumizing the lips and perioral area, including less early life impact and early symptoms compared with Restylane-L. Most ISRs and device-related AEs were mild or moderate in severity, and lidocaine effectively managed injection pain.
Juvéderm Volbella Study Group Principal Investigators: Raj Acquilla, MD (Cheshire, United Kingdom) has no financial relationships to disclose; Lakhdar Belhaouari, MD (Toulouse, France) has received research grant support from Allergan for conducting the study; Jonquille Chantrey, MD (Cheshire, United Kingdom) has received research grant support from Allergan for conducting the study; Simon Connolly, MD (Glasgow, United Kingdom) has received a study fee schedule from Allergan, Inc.; David Eccleston, MD (Sutton Coldfield, United Kingdom) has received speaker honoraria from Allergan in the past; Véronique Gassia, MD (Toulouse, France) has received speaker honoraria from Allergan, Inc.; Annelize Meyer, MD (West Sussex, United Kingdom) received funding through Allergan, Inc. to act as an investigator in the study; Tapan Patel, MD (London, United Kingdom) has no financial relationships to disclose; Hervé Raspaldo, MD (Cannes, France) has received honoraria from Allergan, Inc.; Isabelle Rousseaux, MD (Loos, France) has no financial relationships to disclose; Roy Saleh, MD (Cheadle, United Kingdom) has received research grant support from Allergan for conducting the study; Michel Zbili, MD (Nice, France) has no financial relationships to disclose.
1. Coleman SR, Grover R. The anatomy of the aging face: volume loss and changes in 3-dimensional topography. Aesthet Surg J. 2006;26(1S):S4–S9
2. Brandt FS, Cazzaniga A. Hyaluronic acid gel fillers in the management of facial aging. Clin Interv Aging. 2008;3:153–159
3. Belhaouari L. How to enhance lips with hyaluronic acid. Prime. 2011;March:14–21
4. Bogdan Allemann I, Baumann L. Hyaluronic acid gel (Juvéderm) preparations in the treatment of facial wrinkles and folds. Clin Interv Aging. 2008;3:629–634
5. Sarnoff DS, Saini R, Gotkin RH. Comparison of filling agents for lip augmentation. Aesthet Surg J. 2008;28:556–563
6. Beasley KL, Weiss MA, Weiss RA. Hyaluronic acid fillers: a comprehensive review. Facial Plast Surg. 2009;25:86–94
7. Eccleston D, Murphy DK. Juvéderm® Volbella™ in the perioral area: a 12-month prospective, multicenter, open-label study. Clin Cosmet Investig Dermatol. 2012;5:167–172
8. Pusic AL, Klassen AF, Scott AM, et al. Development and psychometric evaluation of the FACE-Q satisfaction with appearance scale: a new patient-reported outcome instrument for facial aesthetics patients. Clin Plast Surg. 2013;40:249–260
9. Werschler WP, Fagien S, Thomas J, et al. Development and validation of a photographic scale for assessment of lip fullness. Aesthet Surg J. 2015 in press
10. Klassen AF, Cano SJ, Scott A, et al. Measuring patient-reported outcomes in facial aesthetic patients: development of the FACE-Q. Facial Plast Surg. 2010;26:303–309
11. Cohen JL, Thomas J, Paradkar D, et al. An interrater and intrarater reliability study of 3 photographic scales for the classification of perioral aesthetic features. Dermatol Surg. 2014;40:663–670
12. Fagien S, Maas C, Murphy DK, et al.Juvéderm Lips Study Group. Juvederm ultra for lip enhancement: an open-label, multicenter study. Aesthet Surg J. 2013;33:414–420
13. Raspaldo H. Injection of a new hyaluronic acid (HA) in the peri-ocular area to reduce tear trough deformities and sunken eyes: retrospective study based on 120 cases [Poster]Presented at: Anti-Aging Medicine World CongressApril 3–5, 2014Monte Carlo, Monaco
© 2015 American Society of Plastic Surgeons
14. Glogau RG, Bank D, Brandt F, et al. A randomized, evaluator-blinded, controlled study of the effectiveness and safety of small gel particle hyaluronic acid for lip augmentation. Dermatol Surg. 2012;38(7, Part 2):1180–1192