Efficacy and Safety of Flexible Hyaluronic Acid Fillers in Lip and Perioral Enhancement

April 2021 | Volume 20 | Issue 4 | Original Article | 402 | Copyright © April 2021

Published online February 19, 2021

Vince Bertucci MD FRCPCa, Andreas Nikolis MDb, Nowell Solish MDc, Vanessa Lane PhDd, Jessica Hicks PhDe

aDivision of Dermatology, University of Toronto, Toronto, Ontario, Canada
bErevna Innovations Clinical Research Unit, Westmount, QC, Canada
cUniversity of Toronto, Toronto, Ontario, Canada
dMedsense Ltd, High Wycombe, UK
eGalderma Laboratories, L.P., Fort Worth, TX

Background: Since lips have a significant role in facial aesthetic perception, lip augmentation is an increasingly popular aesthetic procedure.
Objective: To evaluate aesthetic improvement and facial dynamics with hyaluronic acid (HA) fillers in the lips and perioral region at 8 weeks after the last treatment compared to pre-treatment.
Methods and Materials: In this open-label study, all subjects received HARK in the lips, and an additional group also received HARR and/or HARD in nasolabial folds (NLFs) and marionette lines (MLs). Assessments included aesthetic improvement, naturalness of facial expressions, perception of age, and lip texture.
Results: Nineteen subjects received HARK only; 40 received HARK and HARR and/or HARD. The primary objective was met. All subjects experienced aesthetic improvement in lip fullness at week 8. The investigators also reported aesthetic improvement in all subjects. For the majority of subjects, aesthetic improvement was associated with maintenance of natural and youthful facial expressions, and improved lip texture. Most treatment-emergent adverse events were mild; none were serious.
Conclusion: HARK is a well-tolerated and effective treatment for enhancing lip fullness, maintaining naturalness and youthfulness of facial expressions, and smoothing lip texture, whether used alone or in combination with HARR/ HARD in the NLFs and/or MLs.

J Drugs Dermatol. 20(4): 402-408. doi:10.36849/JDD.2021.5525


Augmentation with hyaluronic acid (HA) dermal fillers is an increasingly popular aesthetic treatment approach to increase volume and improve the shape of the lips, as lips are associated with beauty and youth, and have an important role in facial aesthetic perception.1–3 This procedure is commonly requested by younger subjects, but an older population can also benefit from treatment as lips become thinner with age due to a decrease in collagen and elastin and thinning of the orbicularis oris muscle.4

The goal of lip augmentation is to create full, smooth, naturally contoured lips with the correct balance between the upper and lower lips and well-defined vermilion borders.5–7 It is also important to provide aesthetic improvement without hindering natural facial movement.8

Restylane Kysse (HARK), Restylane Refyne (HARR), and Restylane Defyne (HARD) are hyaluronic acid dermal fillers formulated with XpresHAn Technology™ (also known as Optimal Balance Technology (OBT) outside of the US), which is designed to achieve distributed tissue integration, and provide flexibility and support for maintaining natural movement in areas of dynamic expression.9–15 HARK is a product specifically designed for lip augmentation that was recently approved in the US in 2020 and has been approved in various countries outside of the US since 2010.9,16 HARR and HARD have been approved in the US since 2016 and were also used in the current study as add-on treatment for subjects who required lower face correction in addition to lip augmentation to achieve optimal results. HARR and HARD are FDA-approved for injection into the mid‐to‐deep dermis for the correction of moderate‐to‐severe wrinkles and folds, such as NLFs and MLs. The softer gel structure of HARR is most appropriate for moderate wrinkles and folds while the firmer texture and larger gel calibration of HARD is suitable for correction of severe wrinkles and folds.10,11,17,18

In this open-label Phase IV post-marketing study, HARK was evaluated for aesthetic improvement and facial dynamics of